The relationship between SPARC expression in primary tumor and metastatic lymph node of resected pancreatic cancer patients and patients' survival

BACKGROUND： Previous researches in pancreatic cancer demonstrated a negative correlation between secreted protein acidic and rich in cysteine （SPARC） expression in primary tumor and survival, but not for SPARC expression in lymph node. In the present study, we aimed to evaluate the SPARC expression in various types of tissues and its impact on patients＇ prognosis. METHODS： The expression of SPARC was examined by immunohistochemistry in resected pancreatic cancer specimens. Kaplan-Meier analyses and Cox proportional hazards regres- sion were applied to assess the mortality risk. RESULTS： A total of 222 tissue samples from 73 patients were collected to evaluate the SPARC expression, which included 73 paired primary tumor and adjacent normal tissues, 38 paired metastatic and normal lymph nodes. The proportion of posi tive SPARC expression in metastatic lymph node was high （32/38）, whereas in normal lymph node it was negative （0/38）. Positive SPARC expression in primary tumor cells was associ- ated with a significantly decreased overall survival （P=0.007） and disease-free survival （P=0.003）, whereas in other types of tissues it did not show a predictive role for prognosis. Univariate and multivariate analyses both confirmed this significance. CONCLUSION： SPARC can serve a dual function role as both predictor for prognosis and potentially biomarker for lymph node metastasis in resected pancreatic cancer patients.

Altruism and Pricing Strategy in Dual-Channel Supply Chains

With the development of behavioral operational management, human behavior such as altruism, fairness and trust has received considerable attention. This paper studies the effect of altruism on retailer’s and manufacturer’s pricing strategy in two classic dual-channel supply chains by presenting Stackelberg game models. The analysis shows that the player’s altruism preference strongly affects their pricing strategies. The more altruistic one player is, the more profits the other player obtains. Moreover, the effect of manufacturer’s altruistic preference is larger than that of retailer’s. In addition, online price is always lower than offline price in dual-channel supply chain, which still holds true considering altruism. The results also reveal that the product web-fit has significant effect on the player’s optimal pricing strategies. The more compatible with online market the product is, the lower the retail price is set, and the more profit the manufacturer obtains whereas the less the retailer gets.

The determinant factors for map resolutions obtained using CryoEM single particle imaging method

The CryoEM single particle structure determination method has recently received broad attention in the field of structural biology. The structures can be resolved to near-atomic resolutions after model reconstructions from a large number of CryoEM images measuring molecules in different orientations. However, the determining factors for reconstructed map resolution need to be further explored. Here, we provide a theoretical framework in conjunction with numerical simulations to gauge the influence of several key factors to CryoEM map resolutions. If the projection image quality allows orientation assignment, then the number of measured projection images and the quality of each measurement(quantified using average signal-to-noise ratio) can be combined to a single factor, which is dominant to the resolution of reconstructed maps. Furthermore, the intrinsic thermal motion of molecules has significant effects on the resolution. These effects can be quantitatively summarized with an analytical formula that provides a theoretical guideline on structure resolutions for given experimental measurements.

Cryo-EM Data Statistics and Theoretical Analysis of KaiC Hexamer

Cryo-electron microscopy(cryo-EM) provides a powerful tool to resolve the structure of biological macromolecules in natural state. One advantage of cryo-EM technology is that different conformation states of a protein complex structure can be simultaneously built, and the distribution of different states can be measured. This provides a tool to push cryo-EM technology beyond just to resolve protein structures, but to obtain the thermodynamic properties of protein machines. Here, we used a deep manifold learning framework to get the conformational landscape of Kai C proteins, and further obtained the thermodynamic properties of this central oscillator component in the circadian clock by means of statistical physics.

Functional predictability of universal gene circuits in diverse microbial hosts

Although the principles of synthetic biology were initially established in model bacteria,microbial producers,extremophiles and gut microbes have now emerged as valuable prokaryotic chassis for biological engineering.Extending the host range in which designed circuits can function reliably and predictably presents a major challenge for the concept of synthetic biology to materialize.In this work,we systematically characterized the cross-species universality of two transcriptional regulatory modules—the T7 RNA polymerase activator module and the repressors module—in three non-model microbes.We found striking linear relationships in circuit activities among different organisms for both modules.Parametrized model fitting revealed host non-specific parameters defining the universality of both modules.Lastly,a genetic NOT gate and a band-pass filter circuit were constructed from these modules and tested in non-model organisms.Combined models employing host non-specific parameters were successful in quantitatively predicting circuit behaviors,underscoring the potential of universal biological parts and predictive modeling in synthetic bioengineering.

Human umbilical cord mesenchymal stem cells for psoriasis:a phase 1/2a,single-arm study

Psoriasis is a common,chronic immune-mediated systemic disease that had no effective and durable treatment.Mesenchymal stem cells(MSCs)have immunomodulatory properties.Therefore,we performed a phase 1/2a,single-arm clinical trial to evaluate the safety and efficacy of human umbilical cord-derived MSCs(UMSCs)in the treatment of psoriasis and to preliminarily explore the possible mechanisms.Seventeen patients with psoriasis were enrolled and received UMsC infusions.Adverse events,laboratory parameters,PASl,and PGA were analyzed.We did not observe obvious side effects during the treatment and 6-month follow-up.A total of 47.1%(8/17)of the psoriasis patients had at least 40%improvement in the PASl score,and 17.6%(3/17)had no sign of disease or minimal disease based on the PGA score.And the efficiency was 25%(2/8)for males and 66.7%(6/9)for females.After UMSC transplantation(UMSCT),the frequencies of Tregs and CD4^(+)memory T cells were significantly increased,and the frequencies of T helper(Th)17 and CD4^(+)naive T cells were significantly decreased in peripheral blood(PB)of psoriasis patients.And all responders showed significant increases in Tregs and CD4^(+)memory T cells,and significant decreases in Th17 cells and serum IL-17 level after UMsCT.And baseline level of Tregs in responders were significantly lower than those in nonresponders.In conclusion,allogeneic UMSCT is safe and partially effective in psoriasis patients,and level of Tregs may be used as a potent biomarker to predict the clinical efficacy of UMSCT.Trial registration Clinical Trials NCT03765957.

Rational design of a biosensor circuit with semi-log dose-response function in Escherichia coli

A central goal of synthetic biology is to apply successful principles that have been developed in electronic and chemical engineering to construct basic biological functional modules, and through rational design, to build synthetic biological systems with predetermined functions. Here, we apply the reverse engineering design principle of biological networks to synthesize a gene circuit that executes semi-log dose-response, a logarithmically linear sensing function, in Escherichia coil cells. We first mathematically define the object function semi-log dose-response, and then search for tri-node network topologies that can most robustly execute the object function. The simplest topology, transcriptional coherent feed-forward loop （TCFL）, among the searching results is mathematically analyzed; we find that, in TCFL topology, the semi-log dose-response function arises from the additive effect of logarithmical linearity intervals of Hill functions. TCFL is then genetically implemented in E. coil as a logarithmically linear sensing biosensor for heavy metal ions [mercury （II）]. Functional characterization shows that this rationally designed biosensor circuit works as expected. Through this study we demonstrated the potential application of biological network reverse engineering to broaden the computational power of synthetic biology.

One-step functionalization of graphene via Diels-Alder reaction for improvement of dispersibility

Good dispersibility of graphene in a medium or matrix is a critical issue in practical applications.In this work,graphene was functionalized using N-(4-hydroxyl phenyl)maleimide(4-HPM)via the Diels—Alder(DA)reaction by a one-step catalyst-free approach.The optimal reaction condition was found to be 90℃for 12 h using dimethytformamide(DMF)as the solvent.FTIR,Raman spectroscopy,XPS and EDS proved that 4-HPM moieties were successfully grafted onto the surface of graphene.UVvis and TGA confirmed that the grafting amount of 4-HPM was 3.75%-3.97%based on the mass of graphene.Functionalized graphene showed excellent dispersion stability when dispersed in common solvents such as ethanol,DMF,water,tetrahydrofuran and pxylene.Meanwhile,functionalized graphene also exhibited pH sensitivity in aqueous due to the phenolic hydroxyls from the 4-HPM moieties.As a result of good dispersion stability and pH sensitivity,compared with graphene,functionalized graphene had better adsorption capacity for methylene blue(MB)from aqueous solution.

Corrigendum to“Improving cooperativity of transcription activators by oligomerization domains in mammalian cells”[Synth Syst Biotechnol 8(1)(2023)114-120]

The authors regret that following the publication of the original article,the authors noticed that Funds in Acknowledgements section was incorrect,in which a fund(No.2020YFA0906903)supporting most of experimental results of Dr.Xinmao Chen was missed by us.We sincerely apologize again for the oversight and appreciate your understanding in allowing us to correct this matter.

Improving cooperativity of transcription activators by oligomerization domains in mammalian cells

Cooperative activation is critical for the applications of synthetic biology in mammalian cells.In this study,we have developed cooperative transcription factor by fusing oligomerization domain in mammalian cells.Firstly,we demonstrated that two oligomerized domains(CI434 and CI)successfully improved transcription factor cooperativity in bacterial cells but failed to increase cooperativity in mammalian cells,possibly because the additional mammalian activation domain disrupted their oligomerization capability.Therefore,we chose a different type of oligomerized domain(CarHC),whose ability to oligomerize is not dependent on its C-terminal domains,to fuse with a transcription factor(RpaR)and activation domain(VTR3),forming a potential cooperative transcription activator RpaR-CarH-VTR3 for mammalian regulatory systems.Compared with RpaR-VTR3,the cooperativity of RpaR-CarH-VTR3 was significantly improved with higher Hill coefficient and a narrower input range in the inducible switch system in mammalian cells.Moreover,a mathematical model based on statistical mechanics model was developed and the simulation results supported the hypothesis that the tetramer of the CarH domain in mammalian cells was the reason for the cooperative capacity of RpaR-CarH-VTR3.