High hyperdiploid karyotype with ≥ 49 chromosomes represents a heterogeneous subgroup of acute myeloid leukemia with differential TP53 mutation status and prognosis: a single-center study from China.

High hyperdiploid karyotype with ≥ 49 chromosomes (which will be referred to as HHK) is rare in acute myeloid leukemia (AML). The European leukemia network (ELN) excluded those harboring only numerical changes (with ≥ 3 chromosome gains) from CK and listed them in the intermediate risk group, while the UK National Cancer Research Institute Adult Leukaemia Working Group classification defined ≥ 4 unrelated chromosome abnormalities as the cutoff for a poorer prognosis. Controversies occurred among studies on the clinical outcome of HHK AML, and their molecular characteristics remained unstudied. We identified 1.31% (133/10,131) HHK cases within our center, among which 48 cases only had numerical changes (NUM), 42 had ELN defined adverse abnormalities (ADV) and 43 had other structural abnormalities (STR). Our study demonstrated that: (1) No statistical significance for overall survival (OS) was observed among three cytogenetic subgroups (NUM, STR and ADV) and HHK AML should be assigned to the adverse cytogenetic risk group. (2) The OS was significantly worse in HHK AML with ≥ 51 chromosomes compared with those with 49-50 chromosomes. (3) The clinical characteristics were similar between NUM and STR group compared to ADV group. The former two groups had higher white blood cell counts and blasts, lower platelet counts, and mutations associated with signaling, while the ADV group exhibited older age, higher chromosome counts, higher percentage of myelodysplastic syndrome (MDS) history, and a dominant TP53 mutation.

The structural basis for activation of the Rab Ypt1p by the TRAPP membrane-tethering complexes.

The multimeric membrane-tethering complexes TRAPPI and TRAPPII share seven subunits, of which four (Bet3p, Bet5p, Trs23p, and Trs31p) are minimally needed to activate the Rab GTPase Ypt1p in an event preceding membrane fusion. Here, we present the structure of a heteropentameric TRAPPI assembly complexed with Ypt1p. We propose that TRAPPI facilitates nucleotide exchange primarily by stabilizing the nucleotide-binding pocket of Ypt1p in an open, solvent-accessible form. Bet3p, Bet5p, and Trs23p interact directly with Ypt1p to stabilize this form, while the C terminus of Bet3p invades the pocket to participate in its remodeling. The Trs31p subunit does not interact directly with the GTPase but allosterically regulates the TRAPPI interface with Ypt1p. Our findings imply that TRAPPII activates Ypt1p by an identical mechanism. This view of a multimeric membrane-tethering assembly complexed with a Rab provides a framework for understanding events preceding membrane fusion at the molecular level.

Plasmacytoid dendritic cells cross-prime naive CD8 T cells by transferring antigen to conventional dendritic cells through exosomes.

Although plasmacytoid dendritic cells (pDCs) have been shown to play a critical role in generating viral immunity and promoting tolerance to suppress antitumor immunity, whether and how pDCs cross-prime CD8 T cells in vivo remain controversial. Using a pDC-targeted vaccine model to deliver antigens specifically to pDCs, we have demonstrated that pDC-targeted vaccination led to strong cross-priming and durable CD8 T cell immunity. Surprisingly, cross-presenting pDCs required conventional DCs (cDCs) to achieve cross-priming in vivo by transferring antigens to cDCs. Taking advantage of an in vitro system where only pDCs had access to antigens, we further demonstrated that cross-presenting pDCs were unable to efficiently prime CD8 T cells by themselves, but conferred antigen-naive cDCs the capability of cross-priming CD8 T cells by transferring antigens to cDCs. Although both cDC1s and cDC2s exhibited similar efficiency in acquiring antigens from pDCs, cDC1s but not cDC2s were required for cross-priming upon pDC-targeted vaccination, suggesting that cDC1s played a critical role in pDC-mediated cross-priming independent of their function in antigen presentation. Antigen transfer from pDCs to cDCs was mediated by previously unreported pDC-derived exosomes (pDCexos), that were also produced by pDCs under various conditions. Importantly, all these pDCexos primed naive antigen-specific CD8 T cells only in the presence of bystander cDCs, similarly to cross-presenting pDCs, thus identifying pDCexo-mediated antigen transfer to cDCs as a mechanism for pDCs to achieve cross-priming. In summary, our data suggest that pDCs employ a unique mechanism of pDCexo-mediated antigen transfer to cDCs for cross-priming.

Dendritic Cell-Based Vaccines Against Cancer: Challenges, Advances and Future Opportunities.

As the most potent professional antigen presenting cells, dendritic cells (DCs) have the ability to activate both naive CD4 and CD8 T cells. Recognized for their exceptional ability to cross-present exogenous antigens to prime naive antigen-specific CD8 T cells, DCs play a critical role in generating CD8 T cell immunity, as well as mediating CD8 T cell tolerance to tumor antigens. Despite the ability to potentiate host CD8 T cell-mediated anti-tumor immunity, current DC-based cancer vaccines have not yet achieved the promised success clinically with the exception of FDA-approved Provenge. Interestingly, recent studies have shown that type 1 conventional DCs (cDC1s) play a critical role in cross-priming tumor-specific CD8 T cells and determining the anti-tumor efficacy of cancer immunotherapies including immune checkpoint blockade (ICB). Together with promising clinical results in neoantigen-based cancer vaccines, there is a great need for DC-based vaccines to be further developed and refined either as monotherapies or in combination with other immunotherapies. In this review, we will present a brief review of DC development and function, discuss recent progress, and provide a perspective on future directions to realize the promising potential of DC-based cancer vaccines.

Inflammatory markers in postoperative cognitive dysfunction for patients undergoing total hip arthroplasty: a meta-analysis.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a poorly understood disorder, very common even after total hip arthroplasty (THA). It is widely considered that inflammation response play a role in the pathogenesis of POCD. AIMS: The aim of the present study was to investigate whether inflammation cytokine concentrations could serve as biomarkers for POCD in patients undergoing THA. METHODS: A systematic search of databases was conducted to retrieve publications measuring circulating inflammatory markers of patients with and without POCD after THA. Inflammatory markers identified in more than two studies were pooled. The standardized mean difference (SMD) and the 95% confidence interval (95% CI) were calculated for each outcome. Fail-safe N statistics was calculated to estimate possible publication bias. RESULTS: The pooled incidence rate of POCD after THA by combining 11 cohort studies was 31%. A total of five inflammatory markers, CRP, S-100B, IL-1ß, IL-6 and TNF-α, were assessed. Significantly higher pre-operative CRP (P = 0.012) and S-100B (P < 0.0001) as well as post-operative CPR (P = 0.005) and IL-6 (P < 0.0001) at 6 h were found in POCD compared with non-POCD patients undergoing THA. Fail-safe N statistics revealed that these results are robust. DISCUSSION: The current evidence suggests that some of the inflammatory markers, including CRP, S-100B, and IL-6, were correlated with the occurrence of POCD after THA. CONCLUSION: Monitor of inflammatory markers might help early diagnosis of POCD after THA and development of preventive strategies.

Effect of wound irrigation on the prevention of surgical site infections: A meta-analysis.

We performed a meta-analysis to evaluate the effect of wound irrigation on the prevention of surgical site infections. A systematic literature search up to January 2022 was done and 24 studies included 4967 subjects under surgery at the start of the study; antibiotic irrigation was used with 1372 of them, 1261 were aqueous povidone-iodine irrigation, and 2334 were saline irrigation or no irrigation for surgical site infections prevention in all surgical populations. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) to evaluate the effect of different wound irrigation on the prevention of surgical site infections by the dichotomous method with a random or fixed-influence model. Antibiotic irrigation had significantly lower surgical site infections in all surgical populations (OR, 0.48; 95% CI, 0.36-0.62, P < .001) compared with saline irrigation or no irrigation for the subject under surgery. Aqueous povidone-iodine irrigation had significantly lower surgical site infections in all surgical populations (OR, 0.40; 95% CI, 0.20-0.81, P = .01) compared with saline irrigation or no irrigation for the subject under surgery. Antibiotic irrigation and aqueous povidone-iodine irrigation significantly lowered surgical site infections in all surgical populations compared with saline irrigation or no irrigation for the subject under surgery. Further studies are required.

Edge-Enhanced with Feedback Attention Network for Image Super-Resolution.

Significant progress has been made in single image super-resolution (SISR) based on deep convolutional neural networks (CNNs). The attention mechanism can capture important features well, and the feedback mechanism can realize the fine-tuning of the output to the input. However, they have not been reasonably applied in the existing deep learning-based SISR methods. Additionally, the results of the existing methods still have serious artifacts and edge blurring. To address these issues, we proposed an Edge-enhanced with Feedback Attention Network for image super-resolution (EFANSR), which comprises three parts. The first part is an SR reconstruction network, which adaptively learns the features of different inputs by integrating channel attention and spatial attention blocks to achieve full utilization of the features. We also introduced feedback mechanism to feed high-level information back to the input and fine-tune the input in the dense spatial and channel attention block. The second part is the edge enhancement network, which obtains a sharp edge through adaptive edge enhancement processing on the output of the first SR network. The final part merges the outputs of the first two parts to obtain the final edge-enhanced SR image. Experimental results show that our method achieves performance comparable to the state-of-the-art methods with lower complexity.

ß-Catenin in dendritic cells exerts opposite functions in cross-priming and maintenance of CD8+ T cells through regulation of IL-10.

Recent studies have demonstrated that ß-catenin in DCs serves as a key mediator in promoting both CD4(+) and CD8(+) T-cell tolerance, although how ß-catenin exerts its functions remains incompletely understood. Here we report that activation of ß-catenin in DCs inhibits cross-priming of CD8(+) T cells by up-regulating mTOR-dependent IL-10, suggesting blocking ß-catenin/mTOR/IL-10 signaling as a viable approach to augment CD8(+) T-cell immunity. However, vaccination of DC-ß-catenin(-/-) (CD11c-specific deletion of ß-catenin) mice surprisingly failed to protect them against tumor challenge. Further studies revealed that DC-ß-catenin(-/-) mice were deficient in generating CD8(+) T-cell immunity despite normal clonal expansion, likely due to impaired IL-10 production by ß-catenin(-/-) DCs. Deletion of ß-catenin in DCs or blocking IL-10 after clonal expansion similarly led to reduced CD8(+) T cells, suggesting that ß-catenin in DCs plays a positive role in CD8(+) T-cell maintenance postclonal expansion through IL-10. Thus, our study has not only identified mTOR/IL-10 as a previously unidentified mechanism for ß-catenin-dependent inhibition of cross-priming, but also uncovered an unexpected positive role that ß-catenin plays in maintenance of CD8(+) T cells. Despite ß-catenin's opposite functions in regulating CD8(+) T-cell responses, selectively blocking ß-catenin with a pharmacological inhibitor during priming phase augmented DC vaccine-induced CD8(+) T-cell immunity and improved antitumor efficacy, suggesting manipulating ß-catenin signaling as a feasible therapeutic strategy to improve DC vaccine efficacy.

[Optimization of extraction technology from compound Huanghuai based on coagulation activity and central composite design-response surface methodology].

To establish a method for the determination of coagulation activity in vitro by using fibrinogen plate method. The extraction route of compound Huanghuai was optimized by selecting thrombin as the reference substance. The comprehensive score of extract yield and the extraction transfer rate of baicalin and rutin was set as the dependent variable, with alcohol concentration, solvent volume and extraction time as the influence factors in central composite design for quadratic fitting, and the extraction process of compound Huanghuai was optimized by using response surface methodology. The results of thrombin concentration and precipitation zone area showed a good linear relationship in 0.4-16 U•mL⁻¹, r=0.997 5. The average recovery rate was 103.8% and the RSD was 4.7 %. The circle of precipitation area of compound Huanghuai combined extract was 38.81 mm², which was bigger than that of fractionated extract. The activity on the daily amount of compound Huanghuai extract was 84.28 U; and the optimum extraction technology was as follows: alcohol concentration 40%, extracted 3 times, the liquid-solid ratio 6∶1, and extraction time 2 h. The predicted value of comprehensive score was 94.26 and the measured value was 88.34, respectively, with a relative deviation of 6.28%. The coagulation activity of the intermediate obtained by optimal extraction process was better. So the method established in this paper was simple, fast and accurate for determination of coagulation activity of compound Huanhuai, which can be also used for the screening of follow-up process and quality control.

[Changes of Serum Gonadal Hormones Levels During Musk-secreting Period and Estrus of Moschus berezovskii].

OBJECTIVE: To detect concentrations of serum gonadal hormones (testosterone, estradiol and progesterone) in musk-secreting period and estrus of Moschus berezovskii, and to study the association of serum gonadal hormones concentrations and musk-secreting. METHODS: The concentrations of serum gonadal hormones were detected with magnetic particle separation ELISA. RESULTS: During musk-secreting period, concentration changes of three serum gonadal hormones showed clear regularity, three crests occurred synchronously. Before musk-secreting period, testosterone, estradiol and progesterone concentrations were at its lower level, in prime musk-secreting period, they increased rapidly to respective highest peak; at later musk-secreting period, they quickly dropped to close to its previous levels before musk-secreting period. During estrus, serum testosterone concentration increased to lower peaks than that at later musk-secreting period. Estradiol remained at a low level and progesterone level was closed to zero. Serum testosterone concentrations in prime musk-secreting period were 114.4 ~ 190.5 times of estrus. During musk-secreting period, there were significant positive correlation among three serum gonadal hormone levels, a positive correlation between musk yield and serum testosterone levels, and negative correlation of musk yield with serum estradiol and progesterone levels as well as musk deer ages. CONCLUSION: Serum testosterone concentrations in prime musk-secreting period increase to the highest levels,which can provide reference in musk secretion induced by artificial means.

Amide and Multihydroxyl Complementary Tailored Metal-Organic Framework with Enhanced Glycan Affinity for Efficient Glycoproteomic Analysis.

Protein glycosylation is ubiquitous and crucial for regulating biological processes in organisms. Given the heterogeneity and low abundance of glycoproteins, efficient and specific enrichment procedures are required for the mass spectrometry analysis of glycopeptides. Hydrophilic interaction liquid chromatography (HILIC) has emerged as an effective strategy for glycopeptide enrichment. However, the relatively weak hydrophilic affinity restricts the achievement of a satisfactory enrichment performance. Here, we presented a rational design of an amide and multihydroxyl complementary tailored metal-organic framework, denoted as U6N/Pv@Glc, which exhibited ultrahydrophilicity and enhanced glycan affinity. Our results demonstrated a significant increase in glycopeptide coverage after enrichment, accompanied by extremely low detection limits (0.05 fmol µL-1) and high selectivity (IgG/BSA, 1:4000) as evaluated using trypsin-digested standard glycoproteins. A total of 379 glycopeptides and 247 intact glycopeptides (containing a total of 1577 site-specific N-glycans) were identified and characterized within human serum samples from individuals with type 2 diabetes in-depth. Additionally, we extended the application of this material to capture undigested glycoproteins, demonstrating potential compatibility with top-down MS analysis. These results highlight the promising potential of this novel material for comprehensive glycoproteomic analysis of every potential aspect.

Investigation of RBM10 mutation and its associations with clinical and molecular characteristics in EGFR-mutant and EGFR-wildtype lung adenocarcinoma.

Background: RBM10 is commonly mutated in lung adenocarcinoma (LUAD). However, its role in the pathogenesis of LUAD remains undefined. EGFR-mutant LUAD represents a distinct subset of non-small cell lung cancer (NSCLC). The function of RBM10 in tumor pathogenesis is supposed to differ between EGFR-mutant and EGFR-wt LUAD. This study aimed to interrogate the prevalence of RBM10 mutation in a large cohort of Chinese patients with LUAD and investigate the association of RBM10 mutation with clinical and molecular characteristics of EGFR-mutant and EGFR-wt LUAD. Methods: Tumor sequencing data from 2848 Chinese patients with LUAD were retrospectively reviewed and analyzed. The prevalence of RBM10 was also compared with other three cohorts: OrigMed (n = 1222), MSKCC (n = 1267), and TCGA (n = 566). The associations of RBM10 mutation with clinical and molecular characteristics were assessed. An external cohort of 182 patients with LUAD who received PD-1 inhibitor were used to investigate the association of RBM10 mutation with clinical outcomes upon immunotherapy. Results: Our cohort showed a higher prevalence of RBM10 in EGFR-mutant LUAD than in EGFR-wt LUAD (14.8 % vs. 6.5 %, p < 0.001). The enrichment of RBM10 mutations in EGFR-mutant LUAD was also seen in another Chinese cohort (OrigMed: 14.9 % vs. 7.8 %, p < 0.001), but not in the two western cohorts (MSKCC: 7.4 % vs. 9.5 %, p = 0.272; TCGA: 8.1 % vs. 6.7 %, p = 0.624). RBM10 mutations co-occurred more frequently with EGFR L858R mutations (23.7 %) than with other types of EGFR mutations (19 del: 7.7 %; other: 7.1 % in others, p < 0.001). In EGFR-mutant LUAD, RBM10 mutations were more commonly found in stage I (18.2 %) and II (21.8 %) vs. stage III (9.4 %) and IV (11.3 %) tumors (p < 0.001). The proportion of PD-L1 positive expression in EGFR-mutant LUAD with concomitant RBM10 mutation was not different from that those without RBM10 mutations (41.8 % vs. 47.9 %, p = 0.566). In contrast, RBM10 mutation occurred more frequently in EGFR-wt LUAD at stage II-IV (stage II: 12.0 %, stage III: 8.7 %, stage IV: 6.6 %) than at stage I (2.8 %). EGFR-wt LUAD with concomitant RBM10 mutations had higher proportions of PD-L1 expression positivity (78.9 % vs. 61.9 %, p = 0.014) and higher tumor mutational load (8.97 vs. 2.99 muts/Mb, p < 0.001) than those without. Patients with EGFR-wt LUAD who also harbored RBM10 loss of function (LOF) mutations had a longer median PFS upon immunotherapy than those with RBM10 non-LOF mutations (7.15 m vs. 2.60 m, HR = 4.83 [1.30-17.94], p = 0.010). Conclusion: We comprehensively investigated RBM10 mutations in a Chinese cohort with LUAD. Compared to western cohorts, a significant enrichment of RBM10 mutations in EGFR-mutant LUAD compared to EGFR-wildtype LUAD in the Chinese population. RBM10 mutation shows different associations with clinical and molecular characteristics between EGFR-mutant and EGFR-wt LUAD, suggesting a divergent mechanism between these two subsets via which RBM10 deficiency contribute to tumor pathogenesis. The findings contribute to our understanding of the molecular landscape of LUAD and highlight the importance of considering population-specific factors in cancer genomics research.

ß-Catenin in Dendritic Cells Negatively Regulates CD8 T Cell Immune Responses through the Immune Checkpoint Molecule Tim-3.

Recent studies have demonstrated that ß-catenin in dendritic cells (DCs) serves as a key mediator in promoting both CD4 and CD8 T cell tolerance, although the mechanisms underlying how ß-catenin exerts its functions remain incompletely understood. Here, we report that activation of ß-catenin leads to the up-regulation of inhibitory molecule T-cell immunoglobulin and mucin domain 3 (Tim-3) in type 1 conventional DCs (cDC1s). Using a cDC1-targeted vaccine model with anti-DEC-205 engineered to express the melanoma antigen human gp100 (anti-DEC-205-hgp100), we demonstrated that CD11c-ß-cateninactive mice exhibited impaired cross-priming and memory responses of gp100-specific CD8 T (Pmel-1) cells upon immunization with anti-DEC-205-hgp100. Single-cell RNA sequencing (scRNA-seq) analysis revealed that ß-catenin in DCs negatively regulated transcription programs for effector function and proliferation of primed Pmel-1 cells, correlating with suppressed CD8 T cell immunity in CD11c-ß-cateninactive mice. Further experiments showed that treating CD11c-ß-cateninactive mice with an anti-Tim-3 antibody upon anti-DEC-205-hgp100 vaccination led to restored cross-priming and memory responses of gp100-specific CD8 T cells, suggesting that anti-Tim-3 treatment likely synergizes with DC vaccines to improve their efficacy. Indeed, treating B16F10-bearing mice with DC vaccines using anti-DEC-205-hgp100 in combination with anti-Tim-3 treatment resulted in significantly reduced tumor growth compared with treatment with the DC vaccine alone. Taken together, we identified the ß-catenin/Tim-3 axis as a potentially novel mechanism to inhibit anti-tumor CD8 T cell immunity and that combination immunotherapy of a DC-targeted vaccine with anti-Tim-3 treatment leads to improved anti-tumor efficacy.

TRAPPI tethers COPII vesicles by binding the coat subunit Sec23.

The budding of endoplasmic reticulum (ER)-derived vesicles is dependent on the COPII coat complex. Coat assembly is initiated when Sar1-GTP recruits the cargo adaptor complex, Sec23/Sec24, by binding to its GTPase-activating protein (GAP) Sec23 (ref. 2). This leads to the capture of transmembrane cargo by Sec24 (refs 3, 4) before the coat is polymerized by the Sec13/Sec31 complex. The initial interaction of a vesicle with its target membrane is mediated by tethers. We report here that in yeast and mammalian cells the tethering complex TRAPPI (ref. 7) binds to the coat subunit Sec23. This event requires the Bet3 subunit. In vitro studies demonstrate that the interaction between Sec23 and Bet3 targets TRAPPI to COPII vesicles to mediate vesicle tethering. We propose that the binding of TRAPPI to Sec23 marks a coated vesicle for fusion with another COPII vesicle or the Golgi apparatus. An implication of these findings is that the intracellular destination of a transport vesicle may be determined in part by its coat and its associated cargo.

Endoscopic manifestations and treatment outcomes of asymptomatic gastric metastases from primary lung adenocarcinoma: Report of two cases.

Metastatic spread of lung adenocarcinoma to the stomach is rare and most gastric metastases are discovered at the advanced stage due to certain symptoms. The present study reported two cases of asymptomatic gastric metastases from lung adenocarcinoma presenting as diminutive nodules or erosion endoscopically. The manifestations were also visualized under magnifying endoscopy with blue laser imaging (BLI-ME), the two cases share certain common characteristics under BLI-ME, such as an obviously widened intervening part and extended subepithelial capillary network, which indicated that lesions developed beneath the superficial epithelium. Target biopsy and further immunohistochemical staining confirmed that the gastric lesions were metastatic from primary lung cancer. None of the two patients were candidates for surgery due to multiple distant metastases, but the gastric metastases regressed to scars after systemic anticancer therapy. These two cases were presented in order to improve the current understanding of the endoscopic manifestations of early gastric metastases from lung cancer, and the outcomes may demonstrate that systemic treatment is effective for eliminating early gastric metastatic lesions.

High-throughput detection of mycophenolic acid in human plasma based on sensitive and rapid fluorescence nitrogen-doped carbon dots sensing platform.

In this experiment, a water-soluble, nitrogen-doped yellow-green fluorescent N-doped carbon dots (N-CDs) were synthesized by one-step hydrothermal method using ß-cyclodextrin as carbon source and L-phenylalanine as nitrogen source. The fluorescence quantum yield of the obtained N-CDs was as high as 9.96%, and the N-CDs exhibited photostability at different pH, ionic strength and temperature. The morphology of the N-CDs was approximately spherical with an average particle size of about 9.4 nm. Based on the fluorescence enhancement effect of mycophenolic acid (MPA) on N-CDs, a quantitative detection method of MPA was established. This method had good selectivity and high sensitivity for MPA. The fluorescence sensing system was applied to the detection of MPA in human plasma. The linear range of MPA were 0.06-3 µg·mL-1 and 3-27 µg·mL-1 with a detection limit of 0.016 µg·mL-1, and the recoveries were 97.03∼100.64 % with the RSDs of 0.13∼2.90 %. The interference experiment results showed that the interference of other coexisting substances, including Fe3+, can be ignored in the actual detection. Comparing the results measured by the established method with the EMIT method, it was found that the results obtained by the two methods were similar, and the relative error was within ± 5 %. This study provided a simple, rapid, sensitive, selective and effective method for the quantitative analysis of MPA, and was expected to be applied to clinical MPA blood concentration monitoring.

Rapid and sensitive fluorescence determination of oxytocin using nitrogen-doped carbon dots as fluorophores.

In this work, a novel nitrogen (N)-doped carbon dots (N-CDs) was prepared with quercetin as the carbon source and o-phenylenediamine as the nitrogen source by hydrothermal synthesis, and their application as fluorophores for selective and sensitive determination of oxytocin were reported. The fluorescence quantum yield of the as-prepared N-CDs, which exhibited good water solubility and photostability, was about 6.45 % using rhodamine 6 G as reference substance, and the maximum excitation (Ex) and emission (Em) wavelength were 460 nm and 542 nm, respectively. The results illustrated that the direct fluorescence quenching of N-CDs fluorophore for the detection of oxytocin achieved good linearity in the range of 0.2-5.0 IU/mL and 5.0-10.0 IU/mL, the correlation coefficients were 0.9954 and 0.9909, respectively, and the detection limit was 0.0196 IU/mL (S/N = 3). The recovery rates were 98.8∼103.8 % with RSD= 0.93 %. The interference experiments showed that common metal ions, possible impurities introduced in production and coexisting excipients in the preparation had little adverse influence on selective detection of oxytocin by the developed N-CDs based fluorescent detection method. The mechanism study on the fluorescence quenching of N-CDs by oxytocin concentrations under the given experimental conditions demonstrated that there were internal filtration effect and static quenching in the system. The developed fluorescence analysis platform for the detection of oxytocin had been proved to be rapid, sensitive, specific and accurate, and to be used for the quality inspection of oxytocin.

Molecular phylogeny reveals cryptic diversity in Sibynophis from China (Serpentes: Sibynophiidae).

The elucidation of species diversity and distribution is critical within the fields of evolution, genetics, and conservation. The genus Sibynophis contains rare snakes that have historically received little attention. In this study, we conducted comprehensive sampling and use both mitochondrial and nuclear genetic markers to explore Sibynophis species diversity within China. Our findings revealed that S. c. miyiensis should be considered synonymous with S. c. grahami, and S. c. grahami should be gave a specific rank as S. grahami. In addition, we discovered S. triangularis was new to China and Myanmar. Based on the specimens and molecular phylogeny results, we redefined the species distribution boundaries of each Chinese species.

Plasmacytoid Dendritic Cells and Cancer Immunotherapy.

Despite largely disappointing clinical trials of dendritic cell (DC)-based vaccines, recent studies have shown that DC-mediated cross-priming plays a critical role in generating anti-tumor CD8 T cell immunity and regulating anti-tumor efficacy of immunotherapies. These new findings thus support further development and refinement of DC-based vaccines as mono-immunotherapy or combinational immunotherapies. One exciting development is recent clinical studies with naturally circulating DCs including plasmacytoid DCs (pDCs). pDC vaccines were particularly intriguing, as pDCs are generally presumed to play a negative role in regulating T cell responses in tumors. Similarly, DC-derived exosomes (DCexos) have been heralded as cell-free therapeutic cancer vaccines that are potentially superior to DC vaccines in overcoming tumor-mediated immunosuppression, although DCexo clinical trials have not led to expected clinical outcomes. Using a pDC-targeted vaccine model, we have recently reported that pDCs required type 1 conventional DCs (cDC1s) for optimal cross-priming by transferring antigens through pDC-derived exosomes (pDCexos), which also cross-prime CD8 T cells in a bystander cDC-dependent manner. Thus, pDCexos could combine the advantages of both cDC1s and pDCs as cancer vaccines to achieve better anti-tumor efficacy. In this review, we will focus on the pDC-based cancer vaccines and discuss potential clinical application of pDCexos in cancer immunotherapy.

ATIC facilitates cell growth and migration by upregulating Myc expression in lung adenocarcinoma.

5-Aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC), a catalysing enzyme in the de novo purine biosynthetic pathway, has been previously reported to be upregulated and to participate in myeloma and hepatocellular carcinoma progression. In the present study, by using bioinformatics technology, a higher ATIC expression was identified in lung adenocarcinoma (LUAD) tissues than in normal tissues, and ATIC expression was found to be positively associated with Myc expression in LUAD tissues. In addition, the role of ATIC in modulating the growth and migration of LUAD cells was explored and the involvement of Myc was revealed. ATIC expression in 56 paired LUAD and tumour adjacent non-cancerous tissues was assessed using reverse transcription-quantitative PCR and western blot analysis. Pearson's correlation analysis was applied to evaluate the correlation between ATIC and Myc expression levels in LUAD tissues. A rescue experiment was performed to explore the role of ATIC/Myc in regulating the growth, migration and invasion of HCC827 and NCI-H1435 cells. It was demonstrated that ATIC was overexpressed in LUAD tissues, particularly in advanced-stage LUAD, and was predicted to be associated with an advanced TNM stage, a higher lymph node metastasis rate, poor tissue differentiation and a lower overall survival rate. ATIC overexpression promoted cell growth, migratory and invasive capacities, whereas this effect was abrogated by Myc knockdown in the HCC827 and NCI-H1435 cells. On the whole, the present study demonstrates that ATIC promotes LUAD cell growth and migration by increasing Myc expression.