Hepatocellular carcinoma and macrophage interaction induced tumor immunosuppressionvia Treg requires TLR4 signaling

AIM: To investigated the interaction between toll-like receptor 4 (TLR4)-activated hepatoma cells and macrophages in the induction of tumor-immune suppression mediated by CD4+CD25high family of transcription factor P3 (FOXP3) regulatory T cells (Tregs). METHODS: The proportion of FOXP3+ Tregs was identified in peripheral blood and tumor tissues of 60 hepatocellular carcinoma (HCC) patients. TLR4 expression was examined in tumor tissues and cell lines. The correlation was examined between FOXP3+ Tregs in peripheral blood and TLR4 expression of HCC tissues. Following activation of TLR4 in H22 murine hepatoma cells pre-incubated with lipopolysaccharide (LPS) and co-cultured with macrophage cell line RAW246.7, the synthesis of cytokines tumor necrosis factor-α, CCL22, and interleukin (IL)-10 by the two cell lines was detected and analyzed. RESULTS: FOXP3+ Tregs were enriched in tumor sites, and circulating FOXP3+ Tregs were increased in HCC patients in correlation with multiple tumor foci and up-regulated TLR4 expression in HCC tissues. Semi-quantitative analysis indicated that TLR4 was over-expressed in HCC compared with the matched normal tissues. Cell cultivation experiments indicated that the mRNAs of IL-10 and CCL22 were significantly up-regulated in the RAW246.7 cell line when co-cultured with LPS preincubated H22 cells. CONCLUSION: In hepatoma cell lines, TLR4 may indirectly facilitate the recruitment of Tregs to the tumor site and promote intrahepatic metastasis through its interaction with macrophages.

Protection against hepatic ischemia/reperfusion injury via downregulation of toll-like receptor 2 expression by inhibition of Kupffer cell function

AIM： To elucidate the mechanism of liver protection by inhibition of Kupffer cells （KCs） function.METHODS： All the animals were randomly divided into three groups. Blockade group （gadolinium chloride solution （GdCl3） injection plus ischemia/reperfusion （I/R） injury）：GdCl3 solution was injected once every 24 h for 2 d via the tail vein before I/R injury. Non-blockade group （saline solution injection plus I/R injury）： saline instead of GdCl3 as a control was injected as in the blockade group. Sham group： saline was injected without I/R injury. Liver samples were collected 4 h after blood inflow restoration. The blockade of the function of KCs was verified by immunostaining with an anti-CD68 mAb. Toll-like receptor2 （TLR2） was immunostained with a goat antimouse polydonal anti-TLR2 antibody. Membrane proteins were extracted from the liver samples and TLR2 protein was analyzed by Western blot. Portal vein serum and plasma were taken respectively at the same time point for further detection of the levels of tumor necrosis factor-α （TNF-α） and alanine aminotransferase （ALT）, an indicator of liver function.I/R injury via downregulation of theexpression of TLR2.RESULTS： Compared to non-blockade group, CD^68＋ cells significantly reduced in blockade group （OPTDI, optical density integral）： 32.97±10.55 vs 185.65±21.88, P〈0.01） and the liver function impairment was relieved partially （level of ALT： 435.89±178.37 U/L vs 890.21±272.91 U/L,P〈0.01）. The expression of TLR2 protein in blockade group significantly decreased compared to that in non- group（method of immunohistochemistry, OPDTI： 75.74±17.44 vs 170.58±25.14, P〈0.01; method of Western blot, A value： 125.89±15.49 vs 433.91±35.53, P〈0.02）. The latter correlated with the variation of CD68 staining （r = 0.745,P〈0.05）. Also the level of portal vein TNF-α decreased in blockade group compared to that in non-blockade group （84.45±14.73 ng/L vs 112.32±17.56 ng/L, P〈0.05）, butwas still higher than that in sham group （84.45±14.73 ng/L vs 6.07±5.33 ng/L, P〈0.01）.CONCLUSION： Inhibition of the function of KCs may protect liver against I/R injury via downregulation of the expression of TLR2.

Physicochemical and environmental characteristics of alkali leaching residue of wolframite and process for valuable metals recovery

Physicochemical and mineralogical characteristics of an alkali leaching residue of wolframite were studied by XRD,SEM−EDS,chemical phase analysis,mineral liberation analyzer(MLA),and TG−DSC methods.Batch leaching tests,toxicity characteristic leaching procedure(TCLP)tests and Chinese standard leaching tests(CSLT)were conducted to determine the environmental mobility of toxic elements.The results show that,due to the high contents of W,Fe,Mn,Sn,and Nb,the residue is with high resource value,but the content of a toxic element,As,is also high.The existing minerals of the investigated elements mainly occur as monomer particles,but it is difficult to extract these valuable metals by conventional acid leaching due to their mineral properties.The release of As increases over time in acidic environment.The leaching concentration of all investigated harmful elements through TCLP is within the limiting value,while the leaching concentration of As through CSLT exceeds the limiting value by more than 4 times,so the residue is classified as hazardous solid waste based on the Chinese standard.A process for valuable metals recovery from this residue was proposed.Preliminary experimental results indicated that the main valuable metals could be extracted effectively.

Endogenous language control in Chinese-English switching: an event-related potentials study

The neural basis of language switching, especially endogenous language control, remains largely unclear. We used a cue-stimulus paradigm and measured behavioral indices and scalp event-related potentials to investigate the endogenous control of switching between Chinese and English. In the experiment, unbalanced Chinese （L1） - English （L2） speakers named pictures in L1 or L2 according to an auditory cue presented 700 ms （cue-stimulus interval） before the picture onset. The reaction time （RT） was longer in the switch condition and the switch cost （difference of RTs between switch and repeat conditions） of L1 （L2→L1） was greater than L2 （L1→L2）. P2 component elicited by the cue onset showed the neural switch cost of L1 at the frontocentral regions, with a leftward distribution, but not the switch cost of L2. The greater switch cost of L1 in behavioral responses and neural activity suggests that the frontocentral areas play an important role in endogenous language control, and switching back to the native language might require more endogenous control.

Tungsten and arsenic substance flow analysis of a hydrometallurgical process for tungsten extracting from wolframite

In this study,the metabolism of a hydrometallurgical process for tungsten extracting from wolframite was studied through substance flow analysis.The mass balance accounts,substance flow charts of tungsten and arsenic were established to evaluate the metabolism efficiency of the investigated system.The results showed that,the total tungsten resource efficiency of the system was 97.56%,and the tungsten recovery of unit process autoclaved alkali leaching,ion exchange,Mo removing,concentration and crystallization was 98.16%,98.94%,99.71%,99.89%,respectively.Meanwhile,for extracting 1 ton of tungsten into the qualified ammonium paratungstate,10.0414 kg of arsenic was carried into the system,with the generation of 7.2801 kg of arsenic in alkali leaching residue,1.5067 kg of tungsten in arsenic waste residue,and 1.2312 kg of tungsten in Mo residue.Besides,7.9 g of arsenic was discharged into nature environment with waste water,15.5 g of arsenic was entrained into the final APT.The distribution and transformation behaviors of arsenic during production were analyzed through phases change analysis,and some recommendations for improving the resource efficiency of tungsten and pollution control during production were also proposed based on the substance flow analysis in this study.

Development and validation of a nomogram for predicting postoperative in-hospital poor outcome in abdominal related emergency general surgery diseases complicated with sepsis

To the Editor:Patients who undergo emergency general surgery(EGS)procedures are up to eight times more likely to die than those undergoing the same procedure electively.[1]The development of an appropriate EGS risk stratification tool could facilitate accurate triage of high-risk patients,thereby supporting surgical decision-making,informed consent,and identification of EGS patients for transfer to a higher level of care.[2]However,the ideal EGS risk stratification tool does not exist yet.In 2016,a uniform system[American Association for the Surgery of Trauma(AAST)grade]for measuring anatomic severity of 16 common EGS diseases has been reported by the AAST Patient Assessment Committee.Simultaneously,the committee pointed out that this system is not intended to serve alone as a predictor of outcome.Other important factors of the outcome,such as physiological status,comorbidities,age,and complexity of operation procedures,should be integrated into the system for risk stratification.[3]In our EGS center,the spectrum of diseases is mainly abdominal related diseases among the 16 diseases including acute appendicitis,acute cholecystitis,acute diverticulitis of the colon,hernias,infectious colitis,intestinal obstruction,acute pancreatitis,pelvic inflammatory disease,perirectal abscess,and perforated peptic ulcer.We have identified abdominal related EGS diseases complicated with sepsis to be a major cause of morbidity and mortality in our EGS center.We assumed that the integration of anatomical severity of EGS diseases plus physiological severity and other parameters(eg,intra-operative variables,age,and comorbidities)together could work better.Thus,this study aimed to develop and validate a nomogram for predicting post-operative in-hospital outcome in abdominal related EGS diseases complicated with sepsis.