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Abstract Food traceability and authentication systems play an important role in ensuring food quality and safety. Current techniques mainly rely on direct measurement by instrumental analysis, which is usually designed for one or a group of specific foods, not available for various food categories. To develop a general strategy for food identification and discrimination, a novel method based on fluorescence sensor arrays is proposed, composed of supramolecular assemblies regulated by non‐covalent interactions as an information conversion system. The stimuli‐responsiveness and tunability of supramolecular assemblies provided an excellent platform for interacting with various molecules in different foods. In this work, five sensor arrays constructed by supramolecular assemblies composed of pyrene derivatives and perylene derivatives are designed and prepared. Assembly behavior and sensing mechanisms are investigated systematically by spectroscopy techniques. The traceability and authentication effects on several kinds of food from different origins or grades are evaluated and verified by linear discriminant analysis (LDA). It is confirmed that the cross‐reactive signals from different sensor units encompassing all molecular interactions can generate a unique fingerprint pattern for each food and can be used for traceability and authentication toward universal food categories with 100% accuracy.

Abstract Background The diagnosis of T-cell lymphomas is typically established through a multiparameter approach that combines clinical, morphologic, immunophenotypic, and genetic features, utilizing a variety of histopathologic and molecular techniques. However, accurate diagnosis of such lymphomas and distinguishing them from reactive lymph nodes remains challenging due to their low prevalence and heterogeneous features, hence limiting the confidence of pathologists. We investigated the use of microRNA (miRNA) expression signatures as an adjunctive tool in the diagnosis and classification of T-cell lymphomas that involve lymph nodes. This study seeks to distinguish reactive lymph nodes (RLN) from two types of frequently occurring nodal T-cell lymphomas: nodal T-follicular helper (TFH) cell lymphomas (nTFHL) and peripheral T-cell lymphomas, not otherwise specified (nPTCL). Methods From the formalin-fixed paraffin-embedded (FFPE) samples from a cohort of 88 subjects, 246 miRNAs were quantified and analyzed by differential expression. Two-class logistic regression and random forest plot models were built to distinguish RLN from the nodal T-cell lymphomas. Gene set enrichment analysis was performed on the target genes of the miRNA to identify pathways and transcription factors that may be regulated by the differentially expressed miRNAs in each subtype. Results Using logistic regression analysis, we identified miRNA signatures that can distinguish RLN from nodal T-cell lymphomas (AUC of 0.92 ± 0.05), from nTFHL (AUC of 0.94 ± 0.05) and from nPTCL (AUC of 0.94 ± 0.08). Random forest plot modelling was also capable of distinguishing between RLN and nodal T-cell lymphomas, but performed worse than logistic regression. However, the miRNA signatures are not able to discriminate between nTFHL and nPTCL, owing to large similarity in miRNA expression patterns. Bioinformatic analysis of the gene targets of unique miRNA expression revealed the enrichment of both known and potentially understudied signalling pathways and genes in such lymphomas. Conclusion This study suggests that miRNA biomarkers may serve as a promising, cost-effective tool to aid the diagnosis of nodal T-cell lymphomas, which can be challenging. Bioinformatic analysis of differentially expressed miRNAs revealed both relevant or understudied signalling pathways that may contribute to the progression and development of each T-cell lymphoma entity. This may help us gain further insight into the biology of T-cell lymphomagenesis.

The structure of mRNA lipid nanoparticles (LNPs) is still under debate, with different studies presenting varying morphological characteristics, significantly hindering their biomedical potential. A typical formulation process of mRNA LNPs involves three steps: initial rapid mixing of lipids in an ethanol phase and mRNA in an acidic aqueous phase, followed by the swift removal of ethanol, and finally adjusting the solution to a neutral environment. In this study, we utilize Small Angle Neutron Scattering (SANS) with contrast matching to reveal the kinetic pathway-dependent of mRNA LNPs morphology. We find that the formulation process of the Moderna COVID-19 vaccine is controlled by a competition between aggregation and microphase separation, dictating the diverse morphologies observed in mRNA LNPs. The first step leads to the formation of polydisperse spherical droplets with an average diameter of 42±6.0 nm in an acidic ethanol aqueous solution. Ethanol removal initiates both aggregation and internal microphase separation, resulting in a polydisperse core-shell structure with an average diameter of 48±3.7 nm. Heptadecan-9-yl 8-((2-hydroxyethyl) (6-oxo-6-(undecyloxy) hexyl) amino) octanoate (SM-102) binds to mRNA via electrostatic interaction to form a reverse-wormlike micelle structure inside. The 1,2-Distearoyl-sn‑glycero-3-phosphocholine (DSPC) and PEG-lipid are just in the shell and cholesterol acting as a filler throughout the core-shell structure. Upon transitioning to a neutral environment, SM-102 loses its charge and neither the periphery nor the reverse-wormlike micelle can maintain their stabilities, leading to further aggregation and microphase separation. The average diameter of core-shell structure turns to be 66±5.2 nm. In the actual formulation process of the Moderna COVID-19 vaccine, steps 2 and 3 occur simultaneously, and the competition between aggregation and microphase separation determines the final morphology. These findings offer crucial insights into optimizing the morphology of mRNA LNPs, thereby facilitating advancements in vaccine development and mRNA vaccine delivery technologies.

Abstract Background Pancreatic adenocarcinoma (PAAD) remains a lethal malignancy making the detection of novel prognostic biomarkers urgent. Limited studies have investigated the predictive capability of immune checkpoints in PAAD. Method Gene expression data and correlative clinical information of PAAD cohort were obtained from public databases, including TCGA, ICGC, GTEX and GEO databases. Risk factors were screened and used to establish a risk score model through LASSO and Cox regression analyses. The prognostic ability of the risk score model was demonstrated. The association between risk score with immune cells infiltration, immune checkpoint genes expression, immunogenic cell death, somatic mutations and signaling pathways enrichment were analysed. scRNA-seq data were collected to confirmed the immune checkpoints expression in PAAD samples. The prognosis prediction ability of OX40/TNFRSF4 was identified. The mRNA and protein expression of OX40 in our clinical specimens were examined by RT-PCR and IHC method and its prognosis ability was verified. Results First of all, the difference of immune microenvironment between pancreatic cancer and adjacent tissues was shown. A risk score system based on three immune checkpoints (OX40, TNFSF14 and KIR3DL1) was established. The risk score model was an independent prognostic factor and performed well regarding overall survival (OS) predictions among PAAD patients. A nomogram was established to facilitate the risk model application in clinical prognosis. Immune cells including naive B cells, CD8+ T cells and Tregs were negatively correlated with the risk score. The risk score was associated with expression of immune checkpoint genes, immunogenic cell death related genes and somatic mutations. Glycolysis processes, IL-2-STAT5, IL-6-STAT3, and mTORC1 signaling pathways were enriched in the high-risk score group. Furthermore, scRNA-seq data confirmed that TNFRSF4, TNFSF14 and KIR3DL1 were expressed on immune cells in PAAD samples. We then identified OX40 as an independent prognosis-related gene, and a higher OX40 expression was associated with increased survival rate and immune environment change. In 84 PAAD clinical specimens collected from our center, we confirmed that higher OX40 mRNA expression levels were related to a good prognosis. The protein expression of OX40 on tumor-infiltrating immune cells (TIICs), endothelial cells and tumor cells was verified in PAAD tissues by immunohistochemistry (IHC) method. Conclusions Overall, our findings strongly suggested that the three-immune checkpoints score system might be useful in the prognosis and design of personalized treatments for PAAD patients. Finally, we identified OX40 as an independent potential biomarker for PAAD prognosis prediction.

Abstract Background Carbohydrate antigen 19–9 (CA19-9) is the most widely used biomarker for pancreatic cancer. Since CA19-9 closely correlates with patient outcome and tumor stage in pancreatic cancer, the deciphering of CA19-9 biosynthesis provides a potential clue for treatment. Methods Concentration of amino acids was detected by ultrahigh-performance liquid chromatography tandem mass spectrometry. Metabolic flux of glutamine was examined by isotope tracing untargeted metabolomics. Label-free quantitative n-glycosylation proteomics was used to examine n-glycosylation alterations. Results Among all amino acids, glutamine was higher in CA19-9-high pancreatic cancers (> 37 U/mL, 66 cases) than in CA19-9-normal clinical specimens (≤ 37 U/mL, 37 cases). The glutamine concentration in clinical specimens was positively correlated with liver metastasis or lymphovascular invasion. Glutamine blockade using diazooxonorleucine suppressed pancreatic cancer growth and intraperitoneal and lymphatic metastasis. Glutamine promotes O-GlcNAcylation, protein glycosylation, and CA19-9 biosynthesis through the hexosamine biosynthetic pathway. UDP-n-acetylglucosamine (UDP-GlcNAc) levels correlated with the glutamine influx through hexosamine biosynthetic pathway and supported CA19-9 biosynthesis. Conclusions Glutamine is a substrate for CA19-9 biosynthesis in pancreatic cancer. Glutamine blockade may be a potential therapeutic strategy for pancreatic cancer.

Abstract Background The extent of pancreatoduodenectomy for pancreatic head cancer remains controversial, and more high‐level clinical evidence is needed. This study aimed to evaluate the outcome of extended pancreatoduodenectomy (EPD) with retroperitoneal nerve resection in pancreatic head cancer. Methods This multicenter randomized trial was performed at 6 Chinese high‐volume hospitals that enrolled patients between October 3, 2012, and September 21, 2017. Four hundred patients with stage I or II pancreatic head cancer and without specific pancreatic cancer treatments (preoperative chemotherapy or chemoradiation) within three months were randomly assigned to undergo standard pancreatoduodenectomy (SPD) or EPD, with the latter followed by dissection of additional lymph nodes (LNs), nerves and soft tissues 270° on the right side surrounding the superior mesenteric artery and celiac axis. The primary endpoint was overall survival (OS) by intention‐to‐treat (ITT). The secondary endpoints were disease‐free survival (DFS), mortality, morbidity, and postoperative pain intensity. Results The R1 rate was slightly lower with EPD (8.46%) than with SPD (12.56%). The morbidity and mortality rates were similar between the two groups. The median OS was similar in the EPD and SPD groups by ITT in the whole study cohort (23.0 vs. 20.2 months, P = 0.100), while the median DFS was superior in the EPD group (16.1 vs. 13.2 months, P = 0.031). Patients with preoperative CA19–9 < 200.0 U/mL had significantly improved OS and DFS with EPD (EPD vs. SPD, 30.8 vs. 20.9 months, P = 0.009; 23.4 vs. 13.5 months, P < 0.001). The EPD group exhibited significantly lower locoregional (16.48% vs. 35.20%, P < 0.001) and mesenteric LN recurrence rates (3.98% vs. 10.06%, P = 0.022). The EPD group exhibited less back pain 6 months postoperation than the SPD group. Conclusions EPD for pancreatic head cancer did not significantly improve OS, but patients with EPD treatment had significantly improved DFS. In the subgroup analysis, improvements in both OS and DFS in the EPD arm were observed in patients with preoperative CA19–9 < 200.0 U/mL. EPD could be used as an effective surgical procedure for patients with pancreatic head cancer, especially those with preoperative CA19–9 < 200.0 U/mL.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent subtype of pancreatic cancer and one of the most malignant tumors worldwide. Due to the heterogeneity of its genomics and proteomics, the prognosis of PDAC remains disappointing despite advances in surgery and medicines. Recently, a novel form of programmed cell death, cuproptosis, was proposed, although its role in PDAC has not been investigated. This study aimed to quantify the expression of cuproptosis-related genes and characterize the novel subtypes of PDAC. Methods: To evaluate the pattern of cuproptosis in PDAC, the gene expression data and clinical information of 372 samples were collected from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A consensus cluster analysis was performed using the transcriptional levels, genetic alterations, and individual prognostic values of seven pre-selected cuproptosis-related genes (DLAT, LIPT1, FDX1, DLD, PDHB, PDHA1, and LIAS) to identify the novel subtypes associated with cuproptosis in PDAC. A univariate Cox regression analysis was used to determine the significant prognostic indicators and cuproptosis scores among the differentially expressed genes (DEGs) between the dividing subclusters, followed by a principal component analysis. The prognostic values, immune profiles, treatment sensitivities, and cuproptosis scores were evaluated between the different subgroups. Results: Seven cuproptosis-related genes showed aberrant expression levels and genetic alterations in the PDAC tumor microenvironment. Among them, LIPT1, LIAS, DLAT, PDHA1, and DLD were significantly correlated with overall survival. Based on the expression profiles of the seven cuproptosis-related genes, three cuproptosis clusters (Clusters A, B, and C) were identified, which were represented by different clinicopathologic features, gene expression levels, and biological processes. A total of 686 DEGs were identified among the three cuproptosis clusters, of which 35 prognosis-related DEGs were selected to further classify the PDAC samples into two subgroups with different survival rates, clinicopathologic features, immune infiltration levels, and drug sensitivities. Higher cuproptosis scores were associated with a significantly poorer prognosis. Conclusion: The cuproptosis subtypes, scores, and relevant genes represent valuable information for assessing the heterogeneity, treatment, and prognosis of PDAC.

The development of organic afterglow materials with sufficient color purity and high quantum efficiency for hyperafterglow is a great challenging. Here, the authors demonstrate an efficient strategy to achieve hyperafterglow emission through sensitizing and stabilizing isolated fluorescence chromophores by integrating multiresonance fluorescence chromophores into afterglow host in a singlecomponent copolymer.

The phase separation behaviour of non-structure protein nsp8 of SARS CoV2 in the primer synthesis mechanism is presented, underpinning the replication of coronavirus.

Abstract Background Intraductal papillary mucinous neoplasms (IPMNs) are characterized by their abundant mucin production and malignant potential. IPMNs of the pancreas are mainly managed according to their radiographic indications, but this approach lacks accuracy with regard to IPMN grading. Therefore, serological biomarkers such as CA19-9 and CA125 (MUC16) should be employed to assist in predicting the invasiveness of IPMNs. Methods We investigated the preoperative serum levels of CA19-9, CA125 and CEA in 381 surgical patients with a definite pathological diagnosis of IPMN from July 2010 to December 2019 at the Shanghai Cancer Center. We calculated the Youden indices of each point on the receiver operating characteristic (ROC) curves to identify the most appropriate cut-off values of CA19-9, CA125 and CEA for recognizing malignant IPMNs. Serological biomarker differences were correlated with clinicopathological features of IPMNs, and diagnostic indices of different scenarios were calculated to find the optimum strategy. Results The malignant group had higher serum levels of CA19-9, CA125 and CEA. According to the ROC curves, the cut-off values of CA19-9, CA125 and CEA were readjusted to 38.3 U/ml, 13.4 U/ml and 5.3 μg/L. CA19-9 elevation was significantly associated with vascular invasion and perineural infiltration. CA125 showed good efficacy in predicting invasive IPMN in the CA19-9-negative subgroup. Conclusions Serological biomarkers are useful and sensitive indicators for recognizing invasive IPMNs. CA19-9 is the most important diagnostic index among all routinely measured serum biomarkers for differentiating malignant from benign IPMNs. CA19-9 should be combined with CA125 to enable more accurate predictions of IPMN malignancy.

Background Tumor-associated tertiary lymphoid structures (TLSs) are functional immune-responsive niches that are not fully understood in pancreatic ductal adenocarcinoma (PDAC).Methods Fluorescent multiplex immunohistochemistry was performed on sequential sections of surgically resected tumor tissues from 380 PDAC patients without preoperative treatment (surgery alone (SA)) and 136 patients pretreated with neoadjuvant treatment (NAT). Multispectral images were processed via machine learning and image processing platforms, inForm V.2.4 and HALO V.3.2; TLS regions were segmented, and the cells were identified and quantified. The cellular composition and immunological properties of TLSs and their adjacent tissues in PDAC were scored and compared, and their association with prognosis was further examined.Results Intratumoral TLSs were identified in 21.1% (80/380) of patients in the SA group and 15.4% (21/136) of patients in the NAT group. In the SA group, the presence of intratumoral TLSs was significantly associated with improved overall survival (OS) and progression-free survival. The existence of intratumoral TLSs was correlated with elevated levels of infiltrating CD8+T, CD4+T, B cells and activated immune cells in adjacent tissues. A nomogram model was generated with TLS presence as a variable, which successfully predicted PDAC patient OS in an external validation cohort (n=123). In the NAT group, samples exhibited a lower proportion of B cells and a higher proportion of regulatory T cells within intratumoral TLSs. Additionally, these TLSs were smaller in size, with a lower overall maturation level and reduced immune cell activation, and the prognostic value of TLS presence was insignificant in the NAT cohort.Conclusion Our study systematically revealed the cellular properties and prognostic values of intratumoral TLSs in PDAC and described the potential impact of NAT on TLS development and function.

MicroRNAs (MiRNAs) are small, non-coding RNA molecules that function in RNA silencing and post-transcriptional regulation of gene expression. We analyzed the differential expression of miRNAs in 119 endometrial carcinomas, measuring their expression in histological subtypes, molecular subtypes, and tumors with CTNNB1 mutations. Tumors were subdivided into histological and molecular subtypes as defined by The Cancer Genome Atlas. The expression levels of 352 miRNAs were quantified using the PanoramiR panel. Mir-449a, mir-449b-5p, and mir-449c-5p were the top three miRNAs showing increased expression in both endometrioid and de-differentiated carcinomas but were not significantly increased in serous and clear cell carcinomas. The miRNAs with the most increased expression in serous and clear cell carcinomas were miR-9-3p and miR-375, respectively. We also identified 62 differentially expressed miRNAs among different molecular subtypes. Using sequential forward selection, we built subtype classification models for some molecular subtypes of endometrial carcinoma, comprising 5 miRNAs for MMR-deficient tumors, 10 miRNAs for p53-mutated tumors, and 3 miRNAs for CTNNB1-mutated tumors, with areas under curves of 0.75, 0.85, and 0.78, respectively. Our findings confirm the differential expression of miRNAs between various endometrial carcinoma subtypes and may have implications for the development of diagnostic and prognostic tools.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a well-known lethal and heterogeneous disease. Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) is an important mutagenic driver that has seldom been investigated in PDAC. Therefore, this study investigated the significance of APOBEC3C in PDAC. First, cytosine deamination-associated mutation signatures were identified in the PDAC cohorts from TCGA and Fudan University Shanghai Cancer Center (FUSCC) datasets, and C > X-enriched kataegis regions were identified in the FUSCC cohort (12 to 27 counts per sample). Patients were stratified according to APOBEC3C expression, and high APOBEC3C expression was found to correlate with a higher motif enrichment score of 5’-CC-3’ and an elevated kataegis count within PCSK5 and NES genes. Second, we compared APOBEC expression in PDAC and normal pancreatic tissues and found that APOBEC3C was substantially upregulated in PDAC. APOBEC3C-overexpressing cell lines were generated to substantiate the effects of APOBEC3C on PDAC genome, including alterations in single-nucleotide variant (SNV) classes (higher proportion of C > T conversions) and the formation of kataegis regions (newly occurring kataegis regions detected in ACHE and MUC6 genes). Three different PDAC cohorts (FUSCC, TCGA, and QCMG) were analysed to evaluate the prognostic value of APOBEC3C, and APOBEC3C overexpression predicted shorter survival. Finally, the APOBEC3C overexpression correalted with the PDAC tumour microenvironment (TME) remodelling, APOBEC3C expression was associated with the invasion of CD4 + T lymphocytes and CD8 + T lymphocytes (cytotoxic T lymphocytes, CTLs), indicating enhanced immune activity and validating the practicality of APOBEC3C for guiding immunotherapy.

Polygonatum cyrtonema Hua is a perennial herbaceous plant of the Polygonatum genus, belonging to the Liliaceae family, with significant medicinal and nutritional value. In China, this species is a traditional medicinal and edible herb with a long history of application and is widely appreciated by the people. However, as the demand for medicinal herbs continues to grow, excessive harvesting has led to the depletion of wild resources and the risk of genetic erosion. In addition, the chaotic cultivation of varieties and the lack of high quality germplasm resources have led to inconsistent quality of medical materials. Therefore, it is urgent to conduct genetic diversity evaluation of this species and establish a sound conservation plan. This study assessed the genetic diversity and population structure of 96 samples collected from seven regions in China using the simple sequence repeat (SSR) molecular marker technology. In this study, a total of 60 alleles (Na) were detected across the 10 polymorphic SSR markers used, with an average of 6.0 alleles generated per locus. The values of polymorphic information content (PIC) values ranged from 0.3396 to 0.8794, with an average value of 0.6430. The average value of the effective number of alleles (Ne) was 2.761, and the average value of the Shannon’s information index (I) was 1.196. The population structure analysis indicates that the Polygonatum cyrtonema Hua germplasm can be classified into three subpopulations (JZ, QY, JD) at the molecular level, which corresponds to the previous subgroups identified based on individual plant phenotypic traits. Analysis of Molecular Variance (AMOVA) showed that 74% of the genetic variation was between individuals within populations in different regions. The phylogenetic analysis of the 96 germplasm samples divided them into three main populations. The QY and JD subpopulations are largely clustered together, which could be attributed to their mountainous distribution and the local climate environment. The genetic differentiation coefficient (Fst) value was low at 0.065, indicating relatively low population differentiation. The ratio of the genetic differentiation coefficient (Fst) between the JZ population and the other two populations (QY and JD) is much higher than the ratio between the QY and JD populations. Based on the clustering results and the ratio of the genetic differentiation coefficient (Fst), it can be inferred that the genetic relationship between the QY and JD subpopulations is closer, with a certain degree of genetic differentiation from the JZ subpopulation. This study supports the conservation of germplasm resources of Polygonatum cyrtonema Hua in China and provides new parental material for germplasm genetic improvement and breeding programs.

The statics and dynamics of supercooled water in the hydration layer of poly(ethylene glycol) (PEG) were studied by a combination of quasi-elastic neutron scattering (QENS) and molecular dynamics (MD) simulations. Two samples, that is, hydrogenated PEG/deuterated water (h-PEG/D2O) and fully deuterated PEG/hydrogenated water (d-PEG/H2O) with the same molar ratio of ethylene glycol (EG) monomer to water, 1:1, are compared. The QENS data of h-PEG/D2O show the dynamics of PEG, and that of d-PEG/H2O reveals the motion of water. The temperature-dependent elastic scattering intensity of both samples has shown transitions at supercooled temperature, and these transition temperatures depend on the energy resolution of the instruments. Therefore, neither one is a phase transition, but undergoes dynamic process. The dynamic of water can be described as an Arrhenius to super-Arrhenius transition, and it reveals the hydrogen bonding network relaxation of hydration water around PEG at supercooled temperature. Since the PEG-water hydrogen bond structural relaxation time from MD is in good agreement with the average relaxation time from QENS (d-PEG/H2O), MD may further reveal the atomic pictures of the supercooled hydration water. It shows that hydration water molecules form a series of pools around the hydrophilic oxygen atom of PEG. At supercooled temperature, they have a more bond ordered structure than bulk water, proceed a trapping sites diffusion on the PEG surface, and facilitate the structural relaxation of PEG backbone.

Twin rectangular-shaped tunnels were constructed vertically beneath the adjacent pipelines in water-rich gravel ground. An analysis was carried out using measured datum to reveal the response of the overlying pipelines to the construction of shallow tunnels. The method of superposition was applied for describing the displacement profile of the overlying pipelines. The transverse profile shapes for the pipelines remain different. The profile of the gas pipeline and box culvert firstly displays a single-trough “n” shape and “U” shape, respectively, whereas the final profile of the pipelines displays an unsymmetrical double-trough “W” shape. It is also found that the safety of the existing pipelines was generally ensured, except for one monitoring point of the box culvert on the right side of the shallow tunnel. It implies that the larger grouting thickness beyond the excavated outline of the shallow tunnel should be conducted in similar cases.

Abstract Recently, charged aerosols are used widely in many applications, such as fog elimination, inactivation of airborne viruses and so on. Atmospheric pressure non‐equilibrium plasma (APNP) have become an efficient way to generate charged aerosols. Except the traditional pin‐plate or wire‐plate APNP sources, the new APNP sources such as large scale corona discharge system and air plasma jet array are introduced. These sources can increase the ion density in open air and generate adjustable large plasma plume, which are helpful in increasing the charging efficiency on aerosols. Although the interactions between plasma and aerosols is quite complicated, the preliminary study suggests that the diffusion charging dominates aerosols below 0.1 μm, field charging dominates aerosols larger than 1 μm, and the photo charging also contributes to aerosols charging. These reactive charged aerosols have shown their potential in the artificial rain enhancement, biomedicine, and material processing. Finally, challenges and opportunities for theoretical, experimental, and application research in related cross‐disciplinary areas are presented to stimulate critical discussions and collaborations in the future.

Abstract Background Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is the first rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP), which plays a pivotal role in the progression of pancreatic ductal adenocarcinoma (PDAC). Therefore, we investigated the prognostic significance of GFPT1 expression in patients with resectable PDAC. Methods We analyzed public datasets to compare GFPT1 expression in tumor tissues and normal/adjacent pancreatic tissues. We measured the relative GFPT1 expression of 134 resected PDAC specimens in our institution, using real-time polymerase chain reaction (PCR). Survival was compared between high and low GFPT1 expression groups using Kaplan-Meier curves and log-rank tests. Multivariate analyses were estimated using Cox regression and logistic regression models. Results GFPT1 is generally upregulated in PDAC tissues, according to the analysis of public datasets. The data from our institution shows that high GFPT1 expression was correlated with a high rate of lymph node (LN) metastasis (p = 0.038) and was an independent risk factor for LN metastasis (odds ratio (OR) = 3.14, 95% confidence interval (CI) = 1.42 to 6.90, P = 0.005). High GFPT1 expression was significantly associated with poor overall survival (OS; P = 0.019) in patients with resected PDAC. The multivariable-adjusted hazard ratio (HR) for mortality when comparing patients with high and low GFPT1 expression was 2.54 (95% CI = 1.35 to 4.79, P = 0.004). Conclusions GFPT1 is generally upregulated in PDAC tissue and is associated with a high risk of LN metastasis and an unfavorable outcome in patients with resectable PDAC, suggesting its crucial role in PDAC progression.

Abstract Graphitic carbon nitride modified with N‐doped graphene quantum dot (N‐GQDs/g‐C3N4) was prepared by an in situ method, in which the g‐C3N4 was synthesized in the presence of N‐GQD. Furthermore, the structure and photocatalytic degradation performance of in situ synthesised N‐GQDs/g‐C3N4 were investigated and compared with N‐GQDs/g‐C3N4 prepared by traditional mixing method. The removal efficiency was about 98.0% for the photocatalytic degradation of RhB after 70 min, which was larger comparing with other GQDs/g‐C3N4 reported in previous works. The result was attributed to uniform distribution of N‐GQDs on surface of g‐C3N4, leading to more photogenerated electrons transfer. This work did not only report a new synthesis method of N‐GQDs/g‐C3N4, but also provided a new method to improve photodegradation performance of photocatalyst based on g‐C3N4.

Due to the rugged construction, high starting torque, wide speed range, inherent fault-tolerance and high operating efficiency, switched reluctance motors (SRMs) have been used in many fields such as household appliances, electric vehicles and industrial drives. At low and medium speeds, the current chopping control (CCC) are usually used for SRMs. The current sensors must be connected in series with each phase winding for detecting the phase current, and the number of sensors is usually equal to the number of motor phases. In order to reduce the number of current sensors and the cost of the drive system, this paper propose a general phase current reconstruction method for SRM drive system with two current sensors. Firstly, the excitation, freewheeling and demagnetization circuits of the asymmetric half-bridge power converter are separated into two different paths. The sensors placement method, winding connection method and calculation formula of each phase current are introduced in detail. Then the influence of the turn-off angles on the overlap interval of each phase current is analyzed, and the proposed reconstruction method is further extended to multi-phase SRM. This method can simplify the current decoupling process and is easy to implement without changing the asymmetric half-bridge topology and operating states. Finally, the feasibility of the proposed phase current reconstruction algorithm is verified by simulation and experiment.

The role of estrogen signaling in antitumor immunology remains unknown for non-traditional sex-biased cancer types such as pancreatic adenocarcinoma (PAAD). Tertiary lymphoid structures (TLS) are active zones composed of multiple types of immune cells, whose presence indicates anti-tumor immune responses. In this study, we employed a 12-chemokine signature to characterize potential gene categories associated with TLS development and identified seventeen major gene categories including estrogen receptors (ERs). Immunohistochemistry staining revealed the expression patterns of three ERs (ERα, ERβ, and GPER) in 174 PAAD samples, and their correlation with clinicopathological characteristics, immune cell infiltration levels, and intratumoral TLS presence was analyzed. The results indicated that ERα (+) and ERβ (+) were correlated with high tumor grade, and ERβ (+) and GPER (+) were correlated with lower TNM stage, and both ERα (+) and GPER (+) displayed a beneficial effect on prognosis in this cohort. Interestingly, positive staining of all three ERs was significantly correlated with the presence of intratumoral TLSs and infiltration of more active immune cells into the microenvironment. Moreover, the chemotaxis of CD8+T-cells to PAAD cells was significantly increased in vitro with upregulated expression of ERα or ERβ on PAAD cells. To conclude, our study showed a novel correlation between ER expression and TLS development, suggesting that ERs may play a protective role by enhancing anti-tumor immune responses in PAAD.

Accurate diagnosis of the most common histological subtypes of small B-cell lymphomas is challenging due to overlapping morphological features and limitations of ancillary testing, which involves a large number of immunostains and molecular investigations. In addition, a common diagnostic challenge is to distinguish reactive lymphoid hyperplasia that do not require additional stains from such lymphomas that need ancillary investigations. We investigated if tissue-specific microRNA (miRNA) expression may provide potential biomarkers to improve the pathology diagnostic workflow. This study seeks to distinguish reactive lymphoid proliferation (RL) from small B-cell lymphomas, and to further distinguish the four main subtypes of small B-cell lymphomas. Two datasets were included: a discovery cohort (n = 100) to screen for differentially expressed miRNAs and a validation cohort (n = 282) to develop classification models. The models were evaluated for accuracy in subtype prediction. MiRNA gene set enrichment was also performed to identify differentially regulated pathways. 306 miRNAs were detected and quantified, resulting in 90-miRNA classification models from which smaller panels of miRNAs biomarkers with good accuracy were derived. Bioinformatic analysis revealed the upregulation of known and other potentially relevant signaling pathways in such lymphomas. In conclusion, this study suggests that miRNA expression profiling may serve as a promising tool to aid the diagnosis of common lymphoid lesions.

Abstract Background Germinomas (IG) account for up to 50% of all intracranial germ cell tumours. These tumours are reputed to be more prevalent in Oriental populations in comparison to Western cohorts. Biological characteristics of IG in other ethnic groups are unknown. Singapore is a multi-ethnic country with diverse cultures. Owing to inter-racial heterogeneity, the authors hypothesize there are molecular differences between paediatric IG patients in our local population. The aims of this study are exploratory: firstly, to identify molecular characteristics in this tumour type and circulating CSF unique to different racial cohorts; and next, to corroborate our findings with published literature. Methods This is a single-institution, retrospective study of prospectively collected data. Inclusion criteria encompass all paediatric patients with histologically confirmed IG. Excess CSF and brain tumour tissues are collected for molecular analysis. Tumour tissues are subjected to a next generation sequencing (NGS) targeted panel for KIT and PDGRA. All CSF samples are profiled via a high-throughput miRNA multiplexed workflow. Results are then corroborated with existing literature and public databases. Results In our cohort of 14 patients, there are KIT exon variants in the tumour tissues and CSF miRNAs corroborative with published studies. Separately, there are also KIT exon variants and miRNAs not previously highlighted in IG. A subgroup analysis demonstrates differential CSF miRNAs between Chinese and Malay IG patients. Conclusion This is the first in-depth molecular study of a mixed ethnic population of paediatric IGs from a Southeast Asian cohort. Validation studies are required to assess the relevance of novel findings in our study.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a malignancy characterized by a poor prognosis and high mortality rate. Genetic mutations and altered molecular pathways serve as targets in precise therapy. Using next-generation sequencing (NGS), these aberrant alterations can be identified and used to develop strategies that will selectively kill cancerous cells in patients with PDAC. The realization of targeted therapies in patients with PDAC may be summarized by three approaches. First, because oncogenes play a pivotal role in tumorigenesis, inhibition of dysregulated oncogenes is a promising method (Table 3). Numerous researchers are developing strategies to target oncogenes, such as KRAS, NRG1, and NTRK and related molecules, although most of the results are unsatisfactory. Accordingly, emerging strategies are being developed to target these oncogenes, including simultaneously inhibiting multiple molecules or pathways, modification of mutant residues by small molecules, and RNA interference. Second, researchers have attempted to reactivate inactivated tumour suppressors or modulate related molecules. TP53, CDKN2A and SMAD4 are three major tumour suppressors involved in PDAC. Advances have been achieved in clinical and preclinical trials of therapies targeting these three genes, and further investigations are warranted. The TGF-β-SMAD4 signalling pathway plays a dual role in PDAC tumorigenesis and participates in mediating tumour-stroma crosstalk and modulating the tumour microenvironment (TME); thus, molecular subtyping of pancreatic cancer according to the SMAD4 mutation status may be a promising precision oncology technique. Finally, genes such as KDM6A and BRCA have vital roles in maintaining the structural stability and physiological functions of normal chromosomes and are deficient in some patients with PDAC, thus serving as potential targets for correcting these deficiencies and precisely killing these aberrant tumour cells. Recent clinical trials, such as the POLO (Pancreas Cancer Olaparib Ongoing) trial, have reported encouraging outcomes. In addition to genetic event-guided treatment, immunotherapies such as chimeric antigen receptor T cells (CAR-T), antibody-drug conjugates, and immune checkpoint inhibitors also exhibit the potential to target tumours precisely, although the clinical value of immunotherapies as treatments for PDAC is still limited. In this review, we focus on recent preclinical and clinical advances in therapies targeting aberrant genes and pathways and predict the future trend of precision oncology for PDAC.

Large-scale public buildings (e.g., stadiums and comprehensive hospitals) in modern cities provide places for various social activities. However, all of these public places encounter the scenario of large passenger flow and crowd gathering, which is highly likely to induce serious safety problems, such as stampedes. Previous studies have shown that efficient evacuation is an important way to ensure the safety of dense crowds in public places. This study aims to explore the optimization methods to improve the evacuation efficiency of public buildings. Two strategies considering plane partition and multi-floor layout are proposed for plane evacuation and vertical evacuation, respectively. Simulation scenarios and models of large stadiums and high-rise hospitals are established to verify the strategies. The results show that plane partition could effectively shorten the total evacuation time, which is due to the optimization of the initial exit choice of individuals and the avoidance of regional congestion in some evacuation channels or exits. Multi-floor layout optimization is an effective management method to arrange the different features of different floors, which could improve the evacuation efficiency for the whole multi-floor building. This study is helpful for building designers and managers to improve the building space layout design and the daily safety management mode.

Background. Pancreatic ductal adenocarcinoma (PDAC) displays a typical mucin expression pattern which is characterized by MUC1 positive, MUC2 negative, and MUC5AC positive. More and more evidences show that mucins are involved in the development of pancreatic diseases. However, the relationship between mucin expression and prognosis of PDAC patients has been controversial in the past decades; therefore, we aim to figure out the association of mucin expression with survival in PDAC patients who underwent radical resection. Methods. We performed immunohistochemistry (IHC) to detect the expression of MUC1, MUC2, and MUC5AC in resected PDAC specimens from Shanghai Cancer Center, Fudan University (FUSCC, n=427) and obtained the corresponding clinical statistical data for retrospective study. Kaplan-Meier methods and Mantel-Cox tests were used to compare the survival curves, and the Cox regression model was employed for multivariate analyses to determine the independent risk factors. Survival analysis was also performed in the Queensland Centre for Medical Genomics (QCMG, n=70) PDAC cohort to verify the conclusion. Results. Both the FUSCC cohort and the QCMG cohort demonstrated that MUC1 absence was significantly correlated with worse overall survival (OS). The presence of MUC2 showed marginal significance in predicting shorter OS of PDAC patients, while MUC5AC had no prognostic value. In the FUSCC cohort, MUC1 absence was associated with increased proportion of stage III PDAC (p=0.011), and MUC1 absence and MUC2 presence were associated with tumour perineural aggression (p=0.011 and p=0.030, respectively). Multivariable adjusted hazard ratios (HRs) for mortality of MUC1 and MUC2 were 0.492 (95% CI: 0.274-0.883, p=0.017) and 1.596 (95% CI: 1.061-2.401, p=0.025), respectively. Conclusions. MUC1 absence or MUC2 presence is independently associated with poor OS among patients with resectable PDAC. MUC5AC absence tended to be associated with short-term death.

Abstract Background As an important epigenetic mark, 5-methylcytosine (5mC) methylation is involved in many DNA-dependent biological processes and plays a role during development and differentiation of multicellular organisms. However, there is still a lack of knowledge about the dynamic aspects and the roles of global 5mC methylation in wood formation in tree trunks. In this study, we not only scrutinized single-base resolution methylomes of primary stems (PS), transitional stems (TS), and secondary stems (SS) of Populus trichocarpa using a high-throughput bisulfite sequencing technique, but also analyzed the effects of 5mC methylation on the expression of genes involved in wood formation. Results The overall average percentages of CG, CHG, and CHH methylation in poplar stems were ~ 53.6%, ~ 37.7%, and ~ 8.5%, respectively, and the differences of 5mC in genome-wide CG/CHG/CHH contexts among PS, TS, and SS were statistically significant (p

Abstract Purpose Kras mutation and abnormal immune status are associated with pancreatic cancer development and progression. In this study, we evaluated the Kras mutation status in circulating tumor DNA and circulating T cell subsets in a cohort of advanced pancreatic cancer patients. Methods Samples were retrospectively obtained from a series of 210 pathological advanced pancreatic cancer patients between 2012 and 2014. The Kras mutation status was detected in cell‐free circulating tumor DNA (ctDNA) by ddPCR and circulating T cell subsets were analyzed by flow cytometry. Results Univariate analysis found that tumor node metastasis (TNM) stage, chemotherapy, circulating regulatory T cells, CA19‐9 levels, CA125 levels, and KrasG12D and KrasG12V mutations were significantly related to overall survival in advanced pancreatic cancer patients. Multivariate analysis identified that TNM stage (P = .03, HR:1.422), Tregs (P = .004, HR:1.522), CA19‐9 levels (P = .009, HR:1.488), KrasG12D mutation (P = .044, HR:1.353), and KrasG12V mutation (P = .001, HR:1.667) were independent prognostic markers. Furthermore, we found that KrasG12V mutation in ctDNA was correlated with high circulating proportion of Tregs, and patients with both KrasG12V mutation and high levels of Tregs were associated with extremely poor survival in advanced pancreatic cancer. Conclusion KrasG12V mutation was associated with high circulating regulatory T cell levels, and both of them predicted worse prognosis in advanced pancreatic cancer patients.

Abstract Gemcitabine (GEM) is the standard chemotherapy drug for pancreatic cancer. Because of widespread drug resistance, the effect is limited. Therefore, it is urgent to reveal the underlying mechanism. Glycolysis is the most remarkable character of tumor aberrant metabolism, which plays vital roles on tumor drug resistance. Hexokinase 2 (HK2), as the key enzyme regulating the first‐step reaction of glycolysis, is overexpressed in many kinds of tumors. The putative role of HK2 resisting GEM therapy was investigated in this study. We found that HK2 was overexpressed in pancreatic cancer and associated with poor prognosis. HK2 knockdown decreased pancreatic cancer cell proliferation, migration viability, and promoted cell apoptosis in vitro. HK2 high expression in pancreatic cancer showed GEM resistance. HK2 knockdown increased the sensitivity of pancreatic cancer cell to GEM, the growth of xenograft tumor with HK2 knockdown was also further decreased with the GEM treatment compared with control in vivo. GEM‐resistant pancreatic cancer showed the increase of HK2 dimer rather than HK2 mRNA or protein. Our study revealed that the ROS derived from GEM promoted HK2 dimerization combining with voltage‐dependent anion channel, which resulted in the resistance to GEM. Meanwhile, our study established a new sight for GEM resistance in pancreatic cancer.

The production of biopellets from agricultural residues is an effective method to overcome the expected shortage in the supply of fuel pellets in the future. This work focused on the new potential applications of fuel pellets to produce liquid and gas fuels through thermochemical and hydrothermal biomass-to-gas technologies. The outcomes also provide a basis to compare the effects of steam and hydrothermal gasification techniques on the properties of product and byproduct, as well as their potentials. For steam gasification, the syngas yield increased from 10.7 to 27.8 mmol/g (on a dry and ash-free basis) by a rise in the gasification temperature at a constant steam-to-biomass ratio. In the case of hydrothermal gasification, there was no carbon monoxide, and hydrogen was the main gas product, and with an increase in the temperature, the hydrogen yield rose from 0.4 mmol/g to 3.17 mmol/g with temperatures from 350 to 650 °C. CO had the largest share in the gas product from steam gasification, which was between 23.3 and 31.3 mol%. The range of the molar ratio of H2/CO for the steam gasification (1.13–1.40) showed the necessity of the further purification of gas products to utilize them as feed for liquid fuel production using the Fischer–Tropsch process. Examination of the mineral content of biochar that remained after the gasification techniques showed large essential elements in them compared with heavy metals, which shows potential for soil amendment. The results highlight the possibility of converting an agricultural residue into a value-added product with potential applications in the energy sector and agriculture.

Liquid crystal spatial light modulators (LC-SLMs) are devices that can accurately adjust the parameters of beam amplitude, phase, wavefront and polarization. However, due to the limitation of laser damage resistance of component materials, LC-SLMs still have difficulty meeting the application and development needs of a high-average power laser system. Here, we proposed an optically addressable spatial light modulator (OASLM) based on a sapphire substrate. Due to the good thermal conductivity of sapphire, the laser damage resistance of the device was greatly improved. The thermal distribution of OASLM based on the sapphire substrate and the K9 substrate is analyzed by a laser-induced temperature rise model. The experimental results also show the excellent performance of sapphire OASLM under high-power CW laser irradiation, its laser power density is increased from 10 W/cm2 to 75 W/cm2, and the working time is more than 30 min. By bonding sapphire to the other side, the laser power density can be increased to 100 W/cm2, and these are completed without active heat dissipation. This method provides a feasible path for high-average-power SLMs.

Noncoding RNAs (ncRNAs), in the form of structural, catalytic or regulatory RNAs, have emerged to be critical effectors of many biological processes. With the advent of new technologies, we have begun to appreciate how intracellular and circulatory ncRNAs elegantly choreograph the regulation of gene expression and protein function(s) in the cell. Armed with this knowledge, the clinical utility of ncRNAs as biomarkers has been recently tested in a wide range of human diseases. In this review, we examine how critical factors govern the success of interrogating ncRNA biomarker expression in liquid biopsies and tissues to enhance our current clinical management of human diseases, particularly in the context of cancer. We also discuss strategies to overcome key challenges that preclude ncRNAs from becoming standard-of-care clinical biomarkers, including sample pre-analytics standardization, data cross-validation with closer attention to discordant findings, as well as correlation with clinical outcomes. Although harnessing multi-modal information from disease-associated noncoding RNome (ncRNome) in biofluids or in tissues using artificial intelligence or machine learning is at the nascent stage, it will undoubtedly fuel the community adoption of precision population health.

We propose a numerical compact model for describing the drain current in ballistic mode by using an expression to represent the transmission coefficients for all operating regions. This model is based on our previous study of an analytic compact model for the subthreshold region in which the DIBL and source-to-drain tunneling effects were both taken into account. This paper introduces an approach to establishing the smoothing function for expressing the critical parameters in the model’s overall operating regions. The resulting compact model was tested in a TCAD NEGF simulation, demonstrating good consistency.

Adipocytic tumors are the most common subtype of soft tissue tumors. In current clinical practice, distinguishing benign lipomas from well-differentiated liposarcomas (WDLPS), as well as dedifferentiated liposarcomas (DDLPS) from their morphologic mimics, remains a significant diagnostic challenge. This is especially so when examining small biopsy samples and without the aid of additional ancillary tests. Recognizing the important role that microRNAs (miRNAs) play in tumorigenesis and their potential utility in tumor classification, we analyzed routine clinical tissue samples of benign and malignant lipomatous tumors, as well as other sarcoma mimics, to identify distinguishing miRNA-based signatures that can aid in the differential diagnosis of these entities. We discovered a 6-miRNA signature that separated lipomas from WDLPS with high confidence (AUC of 0.963), as well as a separate 6-miRNA signature that distinguished DDLPS from their more aggressive histologic mimics (AUC of 0.740). Functional enrichment analysis unveiled possible mechanistic involvement of these predictive miRNAs in adipocytic cancer-related biological processes and pathways such as PI3K/AKT/mTOR and MAPK signaling, further supporting the relevance of these miRNAs as biomarkers for adipocytic tumors. Our results demonstrate that miRNA expression profiling may potentially be used as an adjunctive tool for the diagnosis of benign and malignant adipocytic tumors. Further validation studies are warranted.

A compact nested rotate sextupole permanent magnet (Nest-Rot-SPM) lens was designed for the focusing of pulsed neutrons. It is based on the working conditions of the Very Small Angle Neutron Scattering (VSANS) instrument at the China Spallation Neutron Source (CSNS), and is expected to focus a neutron pulse from 6 Å to 10.5 Å, without chromatic aberration. Three hurdles must be addressed, i.e., the tremendous torque, the heat deposition, and the synchronization with the neutron pulse, respectively. The bore diameter and segment length of the lens are optimized using a formula analysis of the key parameters and model simulations of the torque and heat deposition. A twin torque canceling design is used to reduce the torque to one-third of its original value, or even lower. The goal of this project is to take the device into practical use in the VSANS at the CSNS.

AbstractWe applied miRNA expression profiling method to Populus trichocarpa

Mesenchymal stem cells (MSCs) are of great clinical interest as a form of allogenic therapy due to their excellent regenerative and immunomodulatory effects for various therapeutic indications. Stirred suspension bioreactors using microcarriers (MC) have been used for large-scale production of MSCs compared to planar cultivation systems. Previously, we have demonstrated that expansion of MSCs in MC-spinner cultures improved chondrogenic, osteogenic, and cell migration potentials as compared to monolayer-static cultures. In this study, we sought to address this by analyzing global gene expression patterns, miRNA profiles and secretome under both monolayer-static and MC-spinner cultures in serum-free medium at different growth phases. The datasets revealed differential expression patterns that correlated with potentially improved MSC properties in cells from MC-spinner cultures compared to those of monolayer-static cultures. Transcriptome analysis identified a unique expression signature for cells from MC-spinner cultures, which correlated well with miRNA expression, and cytokine secretion involved in key MSC functions. Importantly, MC-spinner cultures and conditioned medium showed increased expression of factors that possibly enhance pathways of extracellular matrix dynamics, cellular metabolism, differentiation potential, immunoregulatory function, and wound healing. This systematic analysis provides insights for the efficient optimization of stem cell bioprocessing and infers that MC-based bioprocess manufacturing could improve post-expansion cellular properties for stem cell therapies.

In plants, GATA transcription factors (TFs) have been reported to play vital roles in to a wide range of biological processes. To date, there is still no report about the involvement and functions of woody plant GATA TFs in wood formation. In this study, we described the functional characterization of a Populus trichocarpa GATA TF, PtrGATA12, which encodes a nuclear-localized transcriptional activator predominantly expressing in developing xylem tissues. Overexpression of PtrGATA12 not only inhibited growths of most phenotypic traits and biomass accumulation, but also altered the expressions of some master TFs and pathway genes involved in secondary cell wall (SCW) and programmed cell death, leading to alternated SCW components and breaking forces of stems of transgenic lines. The significant changes occurred in the contents of hemicellulose and lignin and SCW thicknesses of fiber and vessel that increased by 13.5 and 10.8%, and 20.83 and 11.83%, respectively. Furthermore, PtrGATA12 bound directly to the promoters of a battery of TFs and pathway genes and activated them; the binding sites include two cis-acting elements that were specifically enriched in their promoter regions. Taken together, our results suggest PtrGATA12, as a higher hierarchical TF on the top of PtrWND6A, PtrWND6B, PtrMYB152, and PtrMYB21, exert a coordinated regulation of SCW components biosynthesis pathways through directly and indirectly controlling master TFs, middle-level TFs, and further downstream pathway genes of the currently known hierarchical transcription network that governs SCW formation.

Abstract Background Both the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging systems have been introduced for pancreatic adenocarcinoma. However, the applicability of these classifications for invasive intraductal papillary mucinous neoplasms (IPMN) has not been systematically examined. Methods Patients with invasive IPMN were retrieved from a cohort of 18 geographical sites (1973–2014 varying) in the Surveillance, Epidemiology, and End Results (SEER) cancer registry. The 7th and 8th editions of the AJCC staging were compared. Survival rates and multivariate analyses were computed. Results In total, 1216 patients with resected invasive IPMN were included. A major difference between the 7th and 8th systems is the definition of stage IIA (7th, beyond the pancreas without involvement of major arteries; 8th, maximum tumor diameter > 4 cm). The hazard ratio (HR) of stage IIA disease (versus stage IA, HR = 2.33, P 2 cm (size > 4 cm versus > 2 ≤ 4 cm, HR = 0.91, P = 0.420). Conclusions The AJCC 7th edition staging classification is more applicable than the 8th edition classification for invasive IPMN.

Abstract Apoptosis resistance is to a large extent a major obstacle leading to chemotherapy failure during cancer treatment. Bypassing the apoptotic pathway to induce cancer cell death is considered to be a promising approach to overcoming this problem. Necroptosis is a regulated necrotic cell death modality in a caspase-independent fashion and is mainly mediated by Receptor-Interacting Protein 1 (RIP1), RIP3, and Mixed Lineage Kinase Domain-Like (MLKL). Necroptosis serves as an alternative mode of programmed cell death overcoming apoptosis resistance and may trigger and amplify antitumor immunity in cancer therapy. The role of necroptosis in cancer is complicated. The expression of key regulators of the necroptotic pathway is generally downregulated in cancer cells, suggesting that cancer cells may also evade necroptosis to survive; however, in certain types of cancer, the expression level of key mediators is elevated. Necroptosis can elicit strong adaptive immune responses that may defend against tumor progression; however, the recruited inflammatory response may also promote tumorigenesis and cancer metastasis, and necroptosis may generate an immunosuppressive tumor microenvironment. Necroptosis also reportedly promotes oncogenesis and cancer metastasis despite evidence demonstrating its antimetastatic role in cancer. In addition, necroptotic microenvironments can direct lineage commitment to determine cancer subtype development in liver cancer. A plethora of compounds and drugs targeting necroptosis exhibit potential antitumor efficacy, but their clinical feasibility must be validated. Better knowledge of the necroptotic pathway mechanism and its physiological and pathological functions is urgently required to solve the remaining mysteries surrounding the role of necroptosis in cancer. In this review, we briefly introduce the molecular mechanism and characteristics of necroptosis, the interplay between necroptosis and other cell death mechanisms, crosstalk of necroptosis and metabolic signaling and detection methods. We also summarize the intricate role of necroptosis in tumor progression, cancer metastasis, prognosis of cancer patients, cancer immunity regulation, cancer subtype determination and cancer therapeutics.

The atomic picture of cellulose dissolution in alkali/urea aqueous solution is still not clear. To reveal it, we use trehalose as the model molecule and total scattering as the main tool. Three kinds of alkali solution, i.e., LiOH, NaOH and KOH are compared. The most probable all-atom structures of the solution are thus obtained. The hydration shell of trehalose has a layered structure. The smaller alkali ions can penetrate into the glucose rings around oxygen atoms to form the first hydration layer. The larger urea molecules interact with hydroxide groups to form complexations. Then, the electronegative complexation can form the second hydration layer around alkali ions via electrostatic interaction. Therefore, the solubility of alkali aqueous solution for cellulose decreases with the alkali cation radius, i.e., LiOH > NaOH > KOH. Our findings are helpful for designing better green solvents for cellulose.

As free-living organisms, bacteria are subject to continuous, numerous and occasionally drastic environmental changes to which they respond with various mechanisms which enable them to adapt to the new conditions so as to survive. Here we describe three situations in which the ribosome and its functions represent the sensor or the target of the stress and play a key role in the subsequent cellular response. The three stress conditions which are described are those ensuing upon: a) zinc starvation; b) nutritional deprivation, and c) temperature downshift.

Trehalose is chosen as a model molecule to investigate the dissolution mechanism of cellulose in NaOH/urea aqueous solution. The combination of neutron total scattering and empirical potential structure refinement yields the most probable all-atom positions in the complex fluid and reveals the cooperative dynamic effects of NaOH, urea, and water molecules in the dissolution process. NaOH directly interacts with glucose rings by breaking the inter- and intra-molecular hydrogen bonding. Na+, thus, accumulates around electronegative oxygen atoms in the hydration shell of trehalose. Its local concentration is thereby 2–9 times higher than that in the bulk fluid. Urea molecules are too large to interpenetrate into trehalose and too complex to form hydrogen bonds with trehalose. They can only participate in the formation of the hydration shell around trehalose via Na+ bridging. As the main component in the complex fluid, water molecules have a disturbed tetrahedral structure in the presence of NaOH and urea. The structure of the mixed solvent does not change when it is cooled to −12 °C. This indicates that the dissolution may be a dynamic process, i.e., a competition between hydration shell formation and inter-molecule hydrogen bonding determines its dissolution. We, therefore, predict that alkali with smaller ions, such as LiOH, has better solubility for cellulose.

In this paper, we propose a fast interference spectral imaging system based on liquid crystal (LC) relaxation. The path delay of nematic LC during falling relaxation is used for the scanning of the optical path. Hyperspectral data can be obtained by Fourier transforming the data according to the path delay. The system can obtain two-dimensional spatial images of arbitrary wavelengths in the range of 300–1100 nm with a spectral resolution of 262 cm−1. Compared with conventional Fourier transform spectroscopy, the system can easily collect and integrate all valid information within 20 s. Based on the LC, controlling the optical path difference between two orthogonally polarized beams can avoid mechanical movement. Finally, the potential for application in contactless and rapid non-destructive optical component defect inspection is demonstrated.

Lymphatic metastasis is a major determinant of the outcome of resected pancreatic cancer. Gemcitabine-based adjuvant chemotherapy can improve the outcome of resected pancreatic cancer. However, the efficacy of gemcitabine against pancreatic cancer stratified by nodal involvement is unclear. In this study, patients who had undergone curative resection of pancreatic adenocarcinoma (612 cases) were included. The efficacy of adjuvant gemcitabine-based regimen, stratified by nodal status (negative, positive) or N substage (N0, no nodal involvement; N1, 1-3-node involvement; N2, ≥4-node involvement), was examined. Both the node-negative (hazard ratio [HR] = 0.62, 95% confidence interval [CI], 0.44-0.87, P = .006) and node-positive subgroups (HR = 0.45, 95% CI, 0.33-0.62, P < .001) benefited from gemcitabine-based adjuvant chemotherapy. Patients with N0 (ie, the node-negative subgroup) or N1 (HR = 0.36, 95% CI, 0.25-0.52, P < .001) disease benefited from gemcitabine-based chemotherapy. However, patients with N2 tumors (HR = 0.95, 95% CI, 0.50-1.78, P = .867) had poor response to gemcitabine-based treatment. Therefore, we postulate that resected pancreatic cancer with N2 node involvement is refractory to gemcitabine-based adjuvant chemotherapy. A more intensive adjuvant regimen may be required for N2 subgroup patients.

Abstract A poor prognosis of pancreatic ductal adenocarcinoma (PDAC) associated with chemoresistance has not changed for the past three decades. A multidisciplinary diagnosis followed by surgery and chemo(radiation)therapy is the main treatment approach. However, gemcitabine- and 5-fluorouracil-based therapies did not present satisfying outcomes. Novel regimens targeting pancreatic cancer cells, the tumor microenvironment, and immunosuppression are emerging. Biomarkers concerning the treatment outcome and patient selection are being discovered in preclinical or clinical studies. Combination therapies of classic chemotherapeutic drugs and novel agents or novel therapeutic combinations might bring hope to the dismal prognosis for PDAC patients.