FGF signaling modulates mechanotransduction/WNT signaling in progenitors during tooth root development

Stem/progenitor cells differentiate into different cell lineages during organ development and morphogenesis.Signaling pathway networks and mechanotransduction are important factors to guide the lineage commitment of stem/progenitor cells during craniofacial tissue morphogenesis.

血液透析患者继发性甲状旁腺功能亢进应用骨化三醇联合西那卡塞治疗的疗效研究

目的:在血液透析患者继发性甲状旁腺功能亢进的治疗中,探究骨化三醇联合西那卡塞的临床效果以及应用的安全性。方法:选择在本院接受治疗的患者,时间在2016年6月至2019年6月,共包括90例,简单随机分组分为对照组和治疗组,每组各45例。对于对照组患者,治疗的方式主要是口服盐酸西那卡塞片,开始服用的剂量为25mg/d,最大剂量控制在75mg/d。而对于治疗组患者,接受对照组患者治疗的基础上同时口服骨化三醇胶丸,开始服用的剂量为每周服用3次,而后根据患者的情况来调整服用的剂量。两组患者均进行3个月的治疗。对两组患者的效果进行分析,同时比较治疗前后两组患者血钙、血磷水平、全段甲状旁腺激素、碱性磷酸酶、甲状旁腺体积的变化情况。结果:治疗组的有效率为93.33%,对照组的有效率为77.77%,治疗组的有效率显著高于对照组(χ^2=4.406,P=0.041)。对患者治疗前后的血钙、血磷水平进行相应的比较,在治疗前均无明显差异(P>0.05);治疗后,治疗组的血磷水平变化幅度大于对照组(P<0.05),而治疗组的血钙水平变化幅度小于对照组(P<0.05)。两组患者的全段甲状旁腺激素、碱性磷酸酶,发现治疗前无显著差异(P>0.05);治疗后,两组患者的全段甲状旁腺激素、碱性磷酸酶均降低、(P<0.05),与对照组相比,治疗组患者变化幅度更大。治疗后,两组患者的甲状旁腺无论长,宽,厚,体积都得到显著改善,治疗组的改善效果更加显著(P<0.05)。结论:在血液透析患者继发性甲状旁腺功能亢进的治疗中,骨化三醇联合西那卡塞具有较好的效果,同时也能够使得甲状旁腺体积明显缩小,进一步控制了不良反应的发生机率。

Tigecycline Use in Surgical Intensive Care Unit for the Treatment of Complicated Intra-Abdominal Infections: A Real-World Study

OBJECTIVES: To describe real-world use of tigecycline in cIAIs patients. METHODS: A retrospective, observational study enrolled cIAIs patients hospitalized in The First Affiliated Hospital, Sun Yat-sen University from January 1, 2013 to June 30, 2017 was conducted. Patients’ data were collected and matched based on age, gender, and Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score according to receiving first-line, later-line, or no tigecycline during hospitalization. RESULTS: Data were collected for 52 patients. 82.6% were male. Mean age was 57.8 years and APACHE II score was 14.8. The incidence of both extended-spectrum beta-lactamase producing and carbapenem-resistant pathogens was high on initial culture;however, few patients received first-line tigecycline. No significant difference in mortality rate was identified among first-line, later-line and no tigecycline users. Of surviving patients, shorter hospital length of stay was observed for patients receiving first- vs later-line or no tigecycline, respectively. ICU length-of-stay was shorter in patients receiving first- vs later-line or no tigecycline. CONCLUSIONS: First-line tigecycline use was rare in our surgical intensive care unit. Resistant organisms were commonly cultured from initial specimens. Although these results are limited by small patient numbers and single center, our results suggest that early tigecycline use may have significant benefits with similar mortality. Further research is warranted to demonstrate the values of early tigecycline use in cIAIs patients.

DKK3在慢性肾小球肾炎中表达及诱导肾小球足细胞迁移的机制研究

目的研究DKK3在慢性肾小球肾炎中的表达,分析DKK3在慢性肾小球肾炎发生、发展中的意义。方法选取人正常肾组织20例、慢性肾小球肾炎组织80例为研究材料,通过实时定量PCR和免疫蛋白印迹实验验证DKK3在人正常肾组织、慢性肾小球肾炎组织中的相对表达;实时定量PCR分析β-catenin mRNA在人正常肾组织、慢性肾小球肾炎组织中的相对表达,Pearson相关性分析DKK3与β-catenin在慢性肾小球肾炎组织中的表达相关性;选取肾小球足细胞MPC5进行DKK3基因过表达,transwell实验验证实验组和对照组中细胞迁移和侵袭的影响;免疫蛋白印迹实验验证DKK3对细胞迁移和侵袭的影响机制。结果与正常肾组织相比,DKK3在慢性肾小球肾炎组织中表达上调(P<0.01),同时DKK3的表达与β-catenin呈正相关性,并参与慢性肾小球肾炎的进展(P=0.0002,r^2=0.1651);DKK3基因过表达后能明显促进细胞迁移和侵袭(P<0.01);免疫蛋白印迹实验显示DKK3基因过表达后能上调Vimentin、N-cadherin、MMP7、β-catenin蛋白的表达,下调E-cadherin蛋白的表达水平(P<0.01)。结论 DKK3在慢性肾小球肾炎组织中表达上调,可能是重要的调控因子参与慢性肾小球肾炎的进展。

A critical review on the health promoting effects of mushrooms nutraceuticals

Extensive elucidations focusing on the efficient health promoting properties and high nutritional values of mushrooms have been expanded dynamically from the past few decades.Due to its high quality of proteins,polysaccharides,unsaturated fatty acids,mineral substances,triterpenes sterols and secondary metabolites,mushrooms have always been appreciated for their vital role in protecting and curing various health problems,such as immunodeficiency,cancer,inflammation,hypertension,hyperlipidemia,hypercholesterolemia and obesity.Moreover,investigations in recent years have revealed the correlations between the health-promoting benefits and gut microbiota regulating effects induced by the mushrooms intake.Researches on the immense role in the nutritional and health benefits displayed by mushrooms have become an emergent task to study.The present article overviewed and compiled the latest information correlated to the health benefits and underlying functional mechanisms of mushroom nutraceuticals,and concluded that the supplementation of mushrooms as a dietary composition could become a natural adjuvant for the prevention and treatment of several health diseases.

Effect of ionic strength and mixing ratio on complex coacervation of soy protein isolate/Flammulina velutipes polysaccharide

Soy protein isolate(SPI)is a commercial protein with balanced amino acids,while the poor solubility impedes its use in traditional foods.To overcome the problem,the complex coacervation of SPI/Flammulina velutipes polysaccharide(FVP)were investigated.Initial results revealed that the suitable amounts of FVP contributed to reducing the turbidity of SPI solution.Under electrostatic interaction,the formation of SPI/FVP coacervates were spontaneous and went through a nucleation and growth process.Low salt concentration(C_(NaCl)=10,50 mmol/L)led to an increase in the critical pH values(pHc,pHφ1)while the critical pH values decreased when C_(NaCl)≥100 mmol/L.The concentration of NaCl ions increased the content ofα-helix.With the increase of FVP,the critical pH values decreased and the content ofβ-sheet increased through electrostatic interaction.At SPI/FVP ratio of 10:1 and 15:1,the complex coacervation of SPI/FVP were saturated,and the coacervates had the same storage modulus value.SPI/FVP coacervates exhibited solid-like properties and presented the strongest storage modulus at C_(NaCl)=50 mmol/L.The optimal pH,SPI/FVP ratio and NaCl concentration of complex coacervation were collected,and the coacervates demonstrated a valuable application potential to protect and deliver bioactives and food ingredients.

Boosting the Electrochemical Performance of Li-and Mn-Rich Cathodes by a Three-in-One Strategy

There are plenty of issues need to be solved before the practi-cal application of Li-and Mn-rich cathodes,including the detrimental voltage decay and mediocre rate capability,etc.Element doping can e ectively solve the above problems,but cause the loss of capacity.The introduction of appropriate defects can compensate the capacity loss;however,it will lead to structural mismatch and stress accumulation.Herein,a three-in-one method that combines cation–polyanion co-doping,defect construction,and stress engineering is pro-posed.The co-doped Na^(+)/SO_(4)^(2-)can stabilize the layer framework and enhance the capacity and voltage stability.The induced defects would activate more reac-tion sites and promote the electrochemical performance.Meanwhile,the unique alternately distributed defect bands and crystal bands structure can alleviate the stress accumulation caused by changes of cell parameters upon cycling.Consequently,the modified sample retains a capacity of 273 mAh g^(-1)with a high-capacity retention of 94.1%after 100 cycles at 0.2 C,and 152 mAh g^(-1)after 1000 cycles at 2 C,the corresponding voltage attenuation is less than 0.907 mV per cycle.

Effect of cooked rice with added fructo-oligosaccharide on faecal microorganisms investigated by in vitro digestion and fermentation

In the present study,the effects of cooked rice(CR)with added fructo-oligosaccharide(FOS)on faecal flora were studied by a simulated in vitro digestion and fermentation method.The total carbohydrate content,p H,and s hort-chain fatty acids(SCFAs)were determined during in vitro digestion and fermentation.The change in the bacterial phase distribution after the fermentation was also analysed.The results showed that t he total carbohydrate content of the CR with added FOS(FCR)significantly decreased during the simulated digestion.Meanwhile,the p H of the FCR decreased and the SCFAs concentration increased significantly compared to those of the CR during the simulated fermentation.In addition,the FCR showed the advantage of promoting beneficial bacteria,such as Bifidobacterium and Lactobacillus,and inhibiting harmful bacteria,such as Bacteroides and Klebsiella compared to the CR.Therefore,the FOS as a prebiotic could be recommended to produce the high-quality healthy rice food.

Expert consensus on the monitoring and treatment of sepsis-induced immunosuppression

Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis.To provide clinical practice recommendations on the immune function in sepsis,an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed.Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed,Web of Science,and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire.Then,the Delphi method was used to form consensus opinions,and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions.This consensus achieved satisfactory results through two rounds of questionnaire survey,with 2 statements rated as perfect consistency,13 as very good consistency,and 9 as good consistency.After summarizing the results,a total of 14 strong recommended opinions,8 weak recommended opinions and 2 non-recommended opinions were produced.Finally,a face-to-face discussion of the consensus opinions was performed through an online meeting,and all judges unanimously agreed on the content of this consensus.In summary,this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.

Amino-modified UiO-66-NH_(2) reinforced polyurethane based polymer electrolytes for high-voltage solid-state lithium metal batteries

Solid-state polymer electrolytes(SPEs)are candidate schemes for meeting the safety and energy density needs of advanced lithium-based battery because of their improved mechanical and electrochemical stability compared to traditional liquid electrolytes.However,low ionic conductivity and side reactions occurring in traditional high-voltage lithium metal batteries(LMBs)hinder their practical applications.Here,amino-modified metal-organic frameworks(UiO-66-NH_(2))with abundant defects as multifunctional fillers in the polyurethane based SPEs achieve the collaborative promotion of the mechanical strength and room temperature ionic conductivity.The surface modified amino groups serve as anchoring points for oxygen atoms of polymer chains,forming a firmly hydrogen-bond interface with polycarbonate-based polyurethane frameworks.The rich interfaces between UiO-66-NH_(2) and polymers dramatically decrease the crystallization of polymer chains and reduce ion transport impedance,which markedly boosted the ionic conductivity to 2.1×10^(−4) S·cm^(−1) with a high Li+transference numbers of 0.71.As a result,LiFePO4∣SPEs∣Li cells exhibit prominent cyclability for 700 cycles under 0.5 C with 96.5%capacity retention.The LiNi_(0.6)Co_(0.2)Mn_(0.2)O_(2)(NCM622)∣SPEs∣Li cells deliver excellent long-term lifespan for 260 cycles with a high capacity retention of 91.9%and high average Coulombic efficiency(98.5%)under ambient conditions.This simple and effective hybrid SPE design strategy sheds a milestone significance light for high-voltage Li-metal batteries.

Clinical practice of sepsis-induced immunosuppression:Current immunotherapy and future options

Sepsis is a potentially fatal condition characterized by the failure of one or more organs due to a disordered host response to infection.The development of sepsis is closely linked to immune dysfunction.As a result,immunotherapy has gained traction as a promising approach to sepsis treatment,as it holds the potential to reverse immunosuppression and restore immune balance,thereby improving the prognosis of septic patients.However,due to the highly heterogeneous nature of sepsis,it is crucial to carefully select the appropriate patient population for immunotherapy.This review summarizes the current and evolved treatments for sepsis-induced immunosuppression to enhance clinicians'understanding and practical application of immunotherapy in the management of sepsis.

Increased Expression of Colonic Mucosal Melatonin in Patients with Irritable Bowel Syndrome Correlated with Gut Dysbiosis

Dysregulation of the gut microbiota/gut hormone axis contributes to the pathogenesis of irritable bowel syndrome(IBS).Melatonin plays a beneficial role in gut motility and immunity.However,altered expression of local mucosal melatonin in IBS and its relationship with the gut microbiota remain unclear.Therefore,we aimed to detect the colonic melatonin levels and microbiota profiles in patients with diarrhea-predominant IBS(IBS-D)and explore their relationship in germ-free(GF)rats and BON-1 cells.Thirty-two IBS-D patients and twenty-eight healthy controls(HCs)were recruited.Fecal specimens from IBS-D patients and HCs were separately transplanted into GF rats by gavage.The levels of colon mucosal melatonin were assessed by immunohistochemical methods,and fecal microbiota communities were analyzed using 16S rDNA sequencing.The effect of butyrate on melatonin synthesis in BON-1 cells was evaluated by ELISA.Melatonin levels were significantly increased and negatively correlated with visceral hypersensitivity in IBS-D patients.GF rats inoculated with fecal microbiota from IBS-D patients had high colonic melatonin levels.Butyrate-producing Clostridium cluster XIVa species,such as Roseburia species and Lachnospira species,were positively related to colonic mucosal melatonin expression.Butyrate significantly increased melatonin secretion in BON-1 cells.Increased melatonin expression may be an adaptive protective mechanism in the development of IBS-D.Moreover,some Clostridium cluster XIVa species could increase melatonin expression via butyrate production.Modulation of the gut hormone/gut microbiota axis offers a promising target of interest for IBS in the future.

DNA recognition patterns of the multi-zinc-finger protein CTCF: a mutagenesis study

CCCTC-binding factor(CTCF) is a zinc-finger protein, serving an important part in the genome architecture as well as some biochemical processes. Over 70,000 CTCF binding DNA sites have been detected genome-wide, and most anchors of chromatin loops are demarcated with the CTCF binding.Various protein or RNA molecules interact with DNA-bound CTCF to conduct different biological functions, and potentially the interfaces between CTCF and its cofactors can be targets for drug development. Here we identify the effective region of CTCF in DNA recognition, which defines the exposed CTCF surface feature for the interaction of cofactors. While the zinc-finger region contributes the most in DNA association, its binding affinity varies based on different DNA sequences. To investigate the effectiveness of individual zinc-fingers, the key residues are mutated to inactivate the DNA binding ability, while the finger configuration and the spacing between fingers are preserved. The strategy is proved to be successful, while clear differences are observed in the DNA binding affinities among the 11 finger mutants and the result is consistent to previous studies in general. With the help of inactivated finger mutants, we identify the ineffective fingers and the dominant effective fingers, which form distinctive patterns on different DNA targets.

Anluohuaxianwan Alleviates Carbon Tetrachloride-Induced Hepatic Fibrosis in Rats through Upregulation of Peroxisome Proliferator-Activated Receptor-Gamma and Downregulation of Nuclear Factor-Kappa B/IκBα Signaling Pathway

Objective:The aim of this study was to investigate the effects of traditional Chinese medicine Anluohuaxianwan(ALHXW)on peroxisome proliferator-activated receptor-gamma(PPARγ)and nuclear factor-kappa B(NF-κB)signaling pathways using a rat model of carbon model groups were gavaged with saline for 6 weeks.Liver function was measured,and liver fibrosis and necroinflammation were assessed.Protein and messenger RNA expression levels of PPARγ,NF-κB,and Inhibitorαof NF-κB(IκBα)were analyzed by Western blot and reverse transcription–quantitative polymerase chain reaction.Results:ALHXW markedly alleviated liver injury compared with the model group,as indicated by the improvements in disease status,the morphology of liver and spleen,the liver and spleen indexes,and liver function.The extent of liver fibrosis was improved,hepatic stellate cell activation was inhibited,the expression of PPARγand IκBαwas significantly higher,and the expression of NF-κB was significantly lower in the treatment group as compared with the model group.Conclusions:ALHXW treatment can alleviate CCl4-induced liver fibrosis in rats, and the potential antifibrogenic mechanisms may occur through the upregulation of PPARγ expression and downregulation of NF-κB/IκBα signaling pathway.