The role of Sigma-1 receptor agonist in hepatic ischemiareperfusion injury.

Sigma-1 receptor (Sig-1R) is a ligand-operated protein that modulates activity of various proteins. It is expressed within the endoplasmic reticulum membranes of multiple organs. We examined the role of Sig-1R in hepatic ischemia-reperfusion injury (IRI). We studied IRI indicators in Sig-1R-/- mice and compared them with wild-type controls. In addition, we assessed the influence of Sig-1R agonist, fluvoxamine, on IRI in both types of animals. We found that Sig-1R-/- mice exhibited significantly decreased liver damage after hepatic IRI as compared to wild-type mice. This effect was manifested by decreased serum levels of alanine aminotransferase (AST), aspartate aminotransferase (ALT), myeloperoxidase (MPO), and supernatant level of lactate dehydrogenase (LDH), decreased endothelial glycocalyx shedding indexed by decreased serum levels of heparan sulfate and syndecan-1, slightly improved liver histology and reduced metalloproteinase-9 expression. Furthermore, in comparison to Sig-1R-/- mice, fluvoxamine significantly increased serum levels of AST, ALT, MPO, and LDH in wildtype animals in a dose-dependent manner at 6 h after IRI. Our findings demonstrate that the absence of Sig-1R provides a protective effect during hepatic IRI. Sig-1R-mediated signaling pathways may play distinct roles in IRI in different organs. The dynamic interaction between Sig-1R and other signaling molecules in different organs needs to be examined further.

Knockdown of lncRNA HCP5 protects against cerebral ischemia/reperfusion injury by regulating miR-652-3p.

Previous studies have shown that lncRNAs play crucial roles in cerebral ischemia/reperfusion injury. In this study, the function and possible mechanism of lncRNA HCP5 in cerebral ischemia/reperfusion injury was investigated. An oxygen glucose deprivation (OGD) model in N2a cells was used to simulate cerebral ischemia/reperfusion injury in vitro. The functional mechanism of lncRNA HCP5 was detected using Trypan blue staining, JC-1, MTT and dual luciferase reporter assays. The expression of apoptosis-related proteins (Bcl-2 and Bax) was measured by Western blot analysis. We found that lncRNA HCP5 was upregulated in N2a cells treated with OGD/R, and knockdown of lncRNA HCP5 enhanced cell viability and reduced cell death. In addition, miR-652-3p was found to act as a sponge for lncRNA HCP5. The overexpression of miR- 652-3p can prevent cerebral ischemic reperfusion injury, however, lncRNA HCP5 attenuated the protective effect of miR-652-3p in cerebral ischemic reperfusion injury. In conclusion, upregulation of lncRNA HCP5 may exacerbate cerebral ischemic reperfusion injury by sponging miR-652-3p.

[Short-term outcomes of total hip arthroplasty in the treatment of Tönnis grade 3 hip osteoarthritis in patients with spondyloepiphyseal dysplasia].

OBJECTIVE: Severe hip osteoarthritis, caused by bone or joint maldevelopment, biomechanical transformation and previous surgical intervention, is inclusively existed in spondyloepiphyseal dysplasia (SED). To investigate and discuss the short-term efficacy and possible effects of total hip arthroplasty in the treatment of Tönnis grade 3 hip osteoarthritis in patients with SED. METHODS: From January 2017 to June 2019, 374 patients with hip osteoarthritis were involved for total hip arthroplasty conducted by senior professional surgeons, of whom 9 patients (6 males and 3 females) with 12 hip osteoarthritis secondary to the SED met the inclusive and exclusive criteria and received the above-mentioned hip operation. The short-term outcomes were observed. RESULTS: All the patients were implanted with Johnson & Johnson ceramic on ceramic cementless hip prostheses within the arthroplasty. They were followed up for an average period of 20 months. Except for one muscular calf vein thrombosis case, no complications, such as aseptic loosening, joint dislocation, fracture, neurovascular injury, deep vein thrombosis and infection were observed in all the 9 patients. Before the surgery, the average Harris hip score was 35.55, while the average of the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) was 56.56. The level of quality of life indicated by SF-12 score was 41.56 on average. The mean pre-operation visual analogue scale (VAS) was 7.44. At the last follow-up, the average Harris hip score increased to 89.56, whereas the average WOMAC declined to 41.11. Compared with the baseline point, the average SF-12 score went up to 56.33. Dramatic drop of the mean VAS value to 2.67 was also observed at the last follow-up. In addition, post-operative increase of several pelvic-related parameters including pelvic incidence, pelvic tilt and sacral slope could be observed in the SED patients. The average measured pelvic incidence, pelvic tilt and sacral slope were 68.95°±4.60°, 52.75°±1.06° and 17.45°±1.77° before operation, respectively; whilst the mean value of these specific parameters increased to 76.98°±5.12°, 60.51°±4.35° and 18.10°±2.02°, respectively. The even leg lengths of the lower extremities were obtained after total hip arthroplasty. CONCLUSION: Total hip arthroplasty is satisfactory in the short-term pain relieve and function recovery for the management of Tönnis grade 3 hip osteoarthritis secondary to the SED.

[Establishment of nutrition literacy core items for Chinese pregnant women].

Objective: To establish the nutrition literacy core items for Chinese pregnant women. Methods: The framework system and preliminary items of nutrition literacy were established through literature review and experts consultation. E-Delphi method was used to determine the nutrition literacy items.11 experts in the field of maternal and child nutrition, obstetrics and gynecology, health education and nutrition and diseases were invited to score the importance of each nutrition literacy item via Email. The judgment basis and familiarity of experts towards the items, active coefficient, authority coefficient and harmony coefficient were evaluated and analyzed to generate the final list of nutrition literacy items. Results: The active coefficients of consultation in two rounds were 81.8% (9/11) and 87.5% (8/9).The authority coefficients were (0.86±0.11) and (0.85±0.06).The average scores of importance were (4.32±0.84) and (4.58±0.57) and the harmony coefficients were 0.387 (χ²=90.472, P<0.001) and 0.290 (χ²=46.752, P=0.002) respectively. After the second round of consultation, all selected items met the inclusion criteria. We identified the final list of nutrition literacy items consisting of 3 scales (basic knowledge and concept, lifestyles and dietary behaviors, and basic skills), 10 sub-scales (basic nutrition concept, food and nutrition knowledge, nutrition and disease knowledge, lifestyles, dietary behaviors, preparation for breastfeeding, gestational weight management, gestational disease management, acquisition, understanding and application of nutrition information, judgement of nutrition information, and nutrition decision making) with 24 items in total. Conclusions: The framework system and core items of nutrition literacy are established for Chinese pregnant women based on E-Delphi method. The experts involved in the consultation process present a performance with good representativeness, enthusiasm and authority. All experts' opinions are coordinated and unified, which could satisfy the demand of developing nutrition literacy core items for target population.

[Establishment of nutrition literacy core items for Chinese lactating women].

Objective: To establish the nutrition literacy core items for Chinese lactating women. Methods: The framework system and preliminary items of nutrition literacy were established through literature review and experts consultation. E-Delphi method was used to determine the nutrition literacy items. 11 experts in the field of maternal and child nutrition, obstetrics and gynecology, health education and nutrition and diseases were invited to score the importance of each nutrition literacy item via Email. The judgment basis and familiarity of experts towards the items, active coefficient, authority coefficient and harmony coefficient were evaluated and analyzed to generate the final list of nutrition literacy items. Results: The active coefficients of consultation in two rounds were 81.8% (9/11) and 87.5% (8/9). The authority coefficients were (0.86±0.11) and (0.85±0.06). The average scores of importance were (4.03±1.24) and (4.64±0.50)and the harmony coefficients were 0.556 (χ²=163.42, P<0.001) and 0.40 (χ²=64.41, P<0.001). After the second round of consultation, all selected items met the inclusion criteria. We identified the final list of nutrition literacy items consisting of 3 scales (basic knowledge and concept, lifestyles and dietary behaviors, and basic skills), 10 subscales (basic nutrition concept, food and nutrition knowledge, feeding knowledge, lifestyles, dietary behaviors, feeding behaviors, weight management, complementary food production, acquisition, understanding and application of nutrition information, judgement of nutrition information, and nutrition decision making) with 24 items in total. Conclusions: The framework system and core items of nutrition literacy were established for Chinese lactating women based on E-Delphi method. The experts involved in the consultation process presented a performance with good representativeness, enthusiasm and authority. All experts' opinions are coordinated and unified, which could satisfy the demand of developing nutrition literacy core items for target population.

Diagnosis and treatment of distal limb microcirculatory disturbance caused by steroid injection.

Corticosteroid is commonly used for the clinical treatment of pain. It is safe, reliable and a simple procedure with other advantages. However, a possible potential catastrophic complication of corticosteroid injections in distal limbs (e.g., the wrist) is acute radial artery ischemia due to the injection into the radial artery. This may result from spasm attributed to the steroids. While the complication of corticosteroids in the wrist is rare, ischemia of the hand caused by corticosteroid injections in radial artery has been reported in several articles. We treated five patients with microcirculation disturbance of distal limb caused by corticosteroid treatment. Here, we report the two different treatment strategies adopted according to the severity of the disease which achieved good therapeutic effects.

Gene structure and expression characteristic of a novel odorant receptor gene cluster in the parasitoid wasp Microplitis mediator (Hymenoptera: Braconidae).

Odorant receptors (ORs) expressed in the antennae of parasitoid wasps are responsible for detection of various lipophilic airborne molecules. In the present study, 107 novel OR genes were identified from Microplitis mediator antennal transcriptome data. Phylogenetic analysis of the set of OR genes from M. mediator and Microplitis demolitor revealed that M. mediator OR (MmedOR) genes can be classified into different subfamilies, and the majority of MmedORs in each subfamily shared high sequence identities and clear orthologous relationships to M. demolitor ORs. Within a subfamily, six MmedOR genes, MmedOR98, 124, 125, 126, 131 and 155, shared a similar gene structure and were tightly linked in the genome. To evaluate whether the clustered MmedOR genes share common regulatory features, the transcription profile and expression characteristics of the six closely related OR genes were investigated in M. mediator. Rapid amplification of cDNA ends-PCR experiments revealed that the OR genes within the cluster were transcribed as single mRNAs, and a bicistronic mRNA for two adjacent genes (MmedOR124 and MmedOR98) was also detected in female antennae by reverse transcription PCR. In situ hybridization experiments indicated that each OR gene within the cluster was expressed in a different number of cells. Moreover, there was no co-expression of the two highly related OR genes, MmedOR124 and MmedOR98, which appeared to be individually expressed in a distinct population of neurons. Overall, there were distinct expression profiles of closely related MmedOR genes from the same cluster in M. mediator. These data provide a basic understanding of the olfactory coding in parasitoid wasps.

Small incision releasing of transverse carpal ligament in diagnosis and treatment of mild carpal tunnel syndrome.

Carpal tunnel syndrome (CTS) is a medical condition due to compression of the median nerve as it travels through the wrist at the carpal tunnel. Few studies have been carried out to examine the effectiveness of mini-open technique for carpal tunnel release using minor wrist skin crease incision in patients with mild CTS. Therefore, the present study was designed to improve the neurophysiological parameters for the diagnosis of mild CTS, and to examine the effectiveness of small incision surgery for the clinical treatment of mild CTS. To this end, we applied the electrophysiological diagnosis of difference between median and ulnar palmar latencies (PMPU) and the difference of median and ulnar latencies from D4 stimulation (D4MD4U) in 80 patients with mild CTS, whom were diagnosed by hand surgeon at the First Hospital of Jilin University. Those patients showed normal in median nerve electrophysiological examination, and received minor wrist skin crease incision surgery. All patients were followed up and received electromyography (EMG) examination. We showed that D4MD4U and PMPU methods are sensitive diagnosis methods for mild CTS, and mini-open wrist crease incision is beneficial for the treatment of mild CTS in clinical settings.

[Unilateral patellar resurfacing in bilateral total knee arthroplasty: a randomized controlled study].

OBJECTIVE: To perform unilateral patellar resurfacing and contralateral patellar retention in bilateral total knee arthroplasty (TKA) randomly, and to compare the clinical effects of patellar retention with patellar resurfacing in TKA. METHODS: In the study, 14 bilateral knee osteoarthritis (OA) patients were randomized in the bilateral TKA to receive unilateral patellar resurfacing and contralateral patellar retention, including 28 knees, all were females, 53 to 78 years old, with average (66.9±7.8) years, and the BMI was (26.3±1.8) kg/m2. All subjects were followed up from 3 to 12 months. The clinical effects were evaluated based on measurements of American Knee Society score (KSS), range of motion (ROM), anterior knee pain, patellar clunk, and patellar tilt angle (PTA). RESULTS: All the wounds healed primarily without significant complications, such as infection, aseptic loosening, patellar fracture and so on. The preoperative KSS scores of patellar resurfacing group were 38.9±22.2, and the scores changed to be 92.4±6.7 after operation, which were added by 53.5±20.3. While in the patellar retention group, the KSS scores were 38.4 ± 20.5 preoperatively, and after operation, which were added to be 92.1±4.2, and improved by 53.7±21.4. The differences in the changed KSS scores between TKA with and without patellar resurfacing were not statistically significant (Independent t-test, P=0.98). The ROM was changed from 95.4°±13.5° preoperatively to 120.4°±8.9° postoperatively in the patellar resurfacing group and from 92.9°±19.1° preoperatively to 120.4±8.4° postoperatively in the patellar retention group. The ROM of the two group were increased by 25.0°±14.5° and 27.5°±19.4° respectively. However, no remarkable differences were observed between the 2 groups in the knee ROM (Independent t-test, P=0.70). At the end of the latest follow-up, 3 knees in the patellar resurfacing group and 2 knees in the patellar retention group had knee anterior pain, the incidences of anterior knee pain were 21.4% and 14.3% respectively. There was no obvious difference for the incidence of post-operative anterior knee pain (Chi-square test, P=0.62). The incidences of post-operative patellar clunk in the 2 groups were all with 3 knees (21.4%), which had no significant difference in the 2 groups (Chi-square test, P=1.00). The post-operative PTA were 2.6°±2.6° in the patellar resurfacing group and 3.6°±2.9° in the patellar retention group, respectively. There was also no statistical difference between the 2 groups (Chi-square test, P=0.36). CONCLUSION: For knee OA patients with mild or moderate patellar cartilage damage, performing patellar resurfacing or not didn't significantly affect anterior knee pain, patellar clunk, functional outcomes or patellar tracking after TKA. So we suggest retain patella in TKA for OA patients with mild or moderate patellar cartilage damage.

[An investigation of normal urinary manganese value in healthy adults in different places in Guangxi, China].

Objective: To investigate the normal urinary manganese value in healthy adults in Guangxi, China and its distribution characteristics. Methods: From 2015 to 2016, stratified random sampling based on age and sex was performed to select 1533 healthy adults aged 18-60 years in Nanning,Liuzhou,Guilin,Hezhou,Wuzhou,Yulin,Guigang,Beihai,Qinzhou,Laibin,Hechi Nandan,Bose Jingxi,Chongzuo Daxin,and Fangchenggang.All of them had no history of occupational manganese exposure or acute or chronic liver/renal diseases and had lived in the local area for more than one year. A total of 1417 urine samples with normal specific gravity and complete data were obtained, and graphite furnace atomic absorption spectrometry was used to measure urinary manganese.The distribution characteristics of urinary manganese level were analyzed among adults with different ages,sexes,or presence or absence of smoking habits or among those who lived or did not live in the mining area. Results: The geometric mean of urinary manganese among healthy adults in Guangxi was 0.52 µg/L,and the upper limit of normal was 5.68µg/L. There was no significant difference in urinary manganese level between the healthy adults with different ages, sexes,or presence or absence of smoking habits (P>0.05).The healthy adults who lived in the mining area of nonferrous metal mines had a significantly higher geometric mean of urinary manganese than those who did not live in such areas(1.65µg/Lvs0.34µg/L,P<0.01). Conclusion: The upper limit of normal of urinary manganese is 5.68 µg/L among healthy adults in Guangxi,and the healthy adults who live in the mining area of manganese mine or nonferrous metal mines have a significantly higher urinary manganese level than those who do not live in such areas.

[Investigation on the normal value of urinary arsenic in healthy people in different areas of Guangxi, China].

Objective: To investigate the upper limit of the normal value of arsenic in healthy adult population in different areas of Guangxi. Methods: From 2015 to 2016, 1533 subjects from 14 counties and cities in Guangxi were collected by age, gender, stratified random sampling and questionnaire survey. 1417 urine samples with satisfactory urine quality and complete information were collected.The content of arsenic in urine was determined by atomic fluorescence spectrometry. Results: The upper limit of normal arsenic in healthy adults in guangxi was 0.053 mg/L. Male urinary arsenicP(50)(0.011mg/L)was higher than that of the female(0.008mg/L), the difference was statistically significant(Z=5.352,P<0.01). Smoking urinary arsenicP(50)(0.012mg/L) was higher than that of nonsmokers(0.009mg/L), the difference was statistically significant(Z=3.404,P<0.01). GroupP(5)0 urine arsenic in coastal areas(0.012mg/L) the crowd was higher than that in non coastal areas(0.009mg/L), the difference was statistically significant(Z=-7.522,P<0.01). Conclusion: The upper limit of normal arsenic in healthy adults in Guangxi area is 0.053mg/L,and there are differences in the levels of arsenic in healthy adults, such as different genders and regions.

Association between ERCC5 gene polymorphisms and gastric cancer risk in a Chinese population.

We conducted a hospital-based case-control study to investigate the association between 3 common SNPs in the ERCC5 gene (rs1047768, rs751402, and rs17655) and the risk of developing gastric cancer. Between January 2013 and December 2014, samples were collected from 216 gastric cancer patients and 216 control subjects. ERCC5 rs1047768, rs751402, and rs17655 polymorphisms were genotyped by polymerase chain reaction combined with restriction fragment length polymorphism analysis. By conditional logistic regression analysis, the GG genotype of rs17655 was found to be associated with an elevated risk of gastric cancer in a codominant model, and the adjusted OR (95%CI) was 1.96 (1.10-3.50). Moreover, in a dominant model, the CG + GG genotype of rs17655 was correlated with an increased risk of gastric cancer compared to the CC genotype (OR = 1.48; 95%CI = 1.00-2.22). rs1047768 and rs751402 were not significantly correlated with an increased or decreased gastric cancer risk.

Structural and biochemical characteristics of chitin-binding protein SeCBP66 from Spodoptera exigua (Hübner).

Peritrophic membrane proteins are important components of the insect peritrophic membrane. A novel cDNA gene encoding a chitin-binding protein, named secbp66, was identified by immunization screening of the cDNA library of Spodoptera exigua. The full length of secbp66 is 1806 bp, which encodes 602 amino acids. The predicted weight of the protein is 64.2 kDa. Bioinformatic analysis showed that a signal peptide composed of 17 amino acids located at the N-terminal of SeCBP66 contained seven tandem putative Type-II functional chitin-binding domains and five potential N-glycosylation sites, but no O-linked glycosylation sites. To study the properties of SeCBP66, recombinant SeCBP66 was successfully expressed in the insect cell line BTI-Tn-5B1-4 with a Bac-to-Bac expression system. A chitin binding experiment showed that the recombinant SeCBP66 protein could bind to chitin strongly. This study of the novel chitin-binding protein SeCBP66 provides a basis for developing new control targets for S. exigua.

Association between the pre-miR-196a2 rs11614913 polymorphism and gastric cancer susceptibility in a Chinese population.

We did a case-control study to provide a more comprehensive evaluation of the association of the pre-miR-196a2 rs11614913 polymorphism with gastric cancer. Between January 2013 and December 2014, 182 patients newly diagnosed with primary gastric cancer and 182 control subjects were recruited at Zhengzhou People's Hospital. For SNP genotyping, we used the Assay Designer 3.1 to design the primers of polymerase chain reaction. Using the chi-square test, we found that patients with gastric cancer were more likely to be alcohol drinkers (χ(2) = 4.4, P = 0.04), to have a family history of cancer in the first relatives (χ(2) = 5.29, P = 0.02), and to be infected with Helicobacter pylori (χ(2) = 23.39, P < 0.001). A significant difference in the genotype distributions of rs11614913 was observed in our study (χ(2) = 6.66, P = 0.04). By logistic regression analysis, we found that the CC genotype of rs11614913 was associated with an increased risk of gastric cancer in a codominant model (OR = 2.68, 95%CI = 1.17-6.44). By stratification analysis, we found that the CC genotype was associated with a strongly increased risk of gastric cancer in drinkers when compared with the TT+TC genotype (OR = 5.63, 95%CI = 1.54-30.76). In conclusion, the results of our study suggest an association between the rs11614913 gene polymorphism and an elevated risk of gastric cancer, especially in drinkers.

Tunable deep-subwavelength superscattering using graphene monolayers.

In this Letter, we theoretically propose for the first time that graphene monolayers can be used for superscatterer designs. We show that the scattering cross-section of the bare deep-subwavelength dielectric cylinder is markedly enhanced by six orders of magnitude due to the excitation of the first-order resonance of graphene plamons. By utilizing the tunability of the plasmonic resonance through tuning graphene's chemical potential, the graphene superscatterer works in a wide range of frequencies from several terahertz to tens of terahertz.

Single nucleotide polymorphisms in the mitochondrial displacement loop and age-at-onset of non-small cell lung cancer.

The associations between single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) and cancer risk and disease outcome have been extensively analyzed. We investigated the association between age-at-onset and SNPs in the mitochondrial D-loop using a population-based series of non-small cell lung cancer (NSCLC) patients. The D-loop region of mtDNA from NSCLC patients was amplified and sequenced. The age-at-onset curve of NSCLC patients was calculated using the Kaplan-Meier method at each SNP site and values were compared using the log-rank test. The SNP sites of nucleotides 200G/A and 16362T/C were identified to determine their association with age-at-onset of NSCLC using the log-rank test. The nucleotide 207G/A was identified for its association with age-at-onset at a borderline significance level (P = 0.060). We found that genetic polymorphisms in the D-loop were predictive markers for age-at-onset in NSCLC patients. Accordingly, the analysis of genetic polymorphisms in the mitochondrial D-loop can be used to identify NSCLC patient subgroups at high risk of early onset.

Shock wave treatment enhances endothelial proliferation via autocrine vascular endothelial growth factor.

Extracorporeal cardiac shock wave (SW) therapy is an effective, safe, and non-invasive therapeutic strategy for severe coronary artery disease. Shock wave therapy might affect cardiac tissues because of its ability to promote angiogenesis. In this report, we investigated if the up-regulation of vascular endothelial growth factor (VEGF) by SW therapy is involved in cell proliferation in cultured endothelial cells. After human umbilical vein endothelial cells were treated with SW, the expression and secretion of VEGF as well as cell proliferation were analyzed. We also determined the mechanism underlying SW-induced the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) using western blotting. Our results demonstrated that SW treatment induced VEGF expression in endothelial cells in a hypoxia-inducible factor 1-independent manner. Up-regulation of VEGF expression led to an increase in its concentration in the cultured medium. The autocrine VEGF in the medium activated the ERK MAPK signaling, which in turn enhanced cell proliferation. Therefore, we concluded that VEGF mediates SW application-induced endothelial cell proliferation in a cell-autonomous manner.

Analysis of the glyco-code in pancreatic ductal adenocarcinoma identifies glycan-mediated immune regulatory circuits.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies with a 5-year survival rate of only 9%. Despite the fact that changes in glycosylation patterns during tumour progression have been reported, no systematic approach has been conducted to evaluate its potential for patient stratification. By analysing publicly available transcriptomic data of patient samples and cell lines, we identified here two specific glycan profiles in PDAC that correlated with progression, clinical outcome and epithelial to mesenchymal transition (EMT) status. These different glycan profiles, confirmed by glycomics, can be distinguished by the expression of O-glycan fucosylated structures, present only in epithelial cells and regulated by the expression of GALNT3. Moreover, these fucosylated glycans can serve as ligands for DC-SIGN positive tumour-associated macrophages, modulating their activation and inducing the production of IL-10. Our results show mechanisms by which the glyco-code contributes to the tolerogenic microenvironment in PDAC.

Modeling and improvement of a low-frequency micro-accelerometer.

A sensitivity- and resolution-improving method for a low-frequency micro-vibration accelerometer is presented in this paper. A sensitivity model of the measurement system is derived and established. The key parameters that limit the sensitivity and the resolution of the accelerometer were identified through the sensitivity coefficient analysis method. The structural parameters and the signal process method were then optimized. Experimental results show that the sensitivity of the accelerometer has improved from 1.10 V/(m/s2) to 19.21 V/(m/s2), and the resolution has improved from 1.47 mm/s2 to 0.21 mm/s2. The lowest working frequency range has expanded from 1 Hz to 0.7 Hz. The presented method is effective and cheap and can be applied to other sensors.

Sialic acids in pancreatic cancer cells drive tumour-associated macrophage differentiation via the Siglec receptors Siglec-7 and Siglec-9.

Changes in glycosylation during tumour progression are a key hallmark of cancer. One of the glycan moieties generally overexpressed in cancer are sialic acids, which can induce immunomodulatory properties via binding to Siglec receptors. We here show that Pancreatic Ductal Adenocarcinoma (PDAC) tumour cells present an increased sialylation that can be recognized by Siglec-7 and Siglec-9 on myeloid cells. We identified the expression of the α2,3 sialyltransferases ST3GAL1 and ST3GAL4 as main contributor to the synthesis of ligands for Siglec-7 and Siglec-9 in tumour cells. Analysing the myeloid composition in PDAC, using single cell and bulk transcriptomics data, we identified monocyte-derived macrophages as contributors to the poor clinical outcome. Tumour-derived sialic acids dictate monocyte to macrophage differentiation via signalling through Siglec-7 and Siglec-9. Moreover, triggering of Siglec-9 in macrophages reduce inflammatory programmes, while increasing PD-L1 and IL-10 expression, illustrating that sialic acids modulate different myeloid cells. This work highlights a critical role for sialylated glycans in controlling immune suppression and provides new potential targets for cancer immunotherapy in PDAC.