Ultralow-power optoelectronic synaptic transistors based on polyzwitterion dielectrics for in-sensor reservoir computing.

Bio-inspired transistor synapses use solid electrolytes to achieve low-power operation and rich synaptic behaviors via ion diffusion and trapping. While these neuromorphic devices hold great promise, they still suffer from challenges such as high leakage currents and power consumption, electrolysis risk, and irreversible conductance changes due to long-range ion migrations and permanent ion trapping. In addition, their response to light is generally limited because of "exciton-polaron quenching", which restricts their potential in in-sensor neuromorphic visions. To address these issues, we propose replacing solid electrolytes with polyzwitterions, where the cation and anion are covalently concatenated via a flexible alkyl chain, thus preventing long-range ion migrations while inducing good photoresponses to the transistors via interfacial charge trapping. Our detailed studies reveal that polyzwitterion-based transistors exhibit optoelectronic synaptic behavior with ultralow-power consumption (~250 aJ per spike) and enable high-performance in-sensor reservoir computing, achieving 95.56% accuracy in perceiving the trajectory of moving basketballs.

Carotenoids synthesis affects the salt tolerance mechanism of Rhodopseudomonas palustris.

Rhodopseudomonas palustris CGA009 is a Gram-negative, purple non-sulfur, metabolically diverse bacterium with wide-ranging habitats. The extraordinary ability of R. palustris to decompose a variety of raw materials and convert them into high-value products makes it an attractive host for biotechnology and industrial applications. However, being a freshwater bacterium R. palustris has limited application in highly-saline environments. Therefore, it is of great significance to obtain the salt-tolerant strain of R. palustris and understand its tolerance mechanism. In this study, R. palustris CGA009 was successfully evolved into eight salt-tolerant strains using an adaptive laboratory evolution technique. RPAS-11 (R. palustris anti-salt strain 11) was selected as the best salt-tolerant strain and was used in further studies to explore the salt-tolerance mechanism. The expression of most genes associated with the carotenoid synthesis in RPAS-11 increased significantly under high concentration of salt stress, suggesting that carotenoid synthesis is one of the reasons for the salt tolerance of RPAS-11. Gene overexpression and knockout experiments were performed to get clear about the role of carotenoids in salt stress tolerance. RPAS-11-IDI, the mutant with overexpression of IDI (Isopentenyl diphosphate isomerase) exhibited enhanced salt tolerance, whereas the knockout mutant CGA009-∆crtI showed a decline in salt tolerance. In addition, the results indicated that rhodopin, a carotenoid compound, was the key pigment responsible for the salt tolerance in R. palustris. Furthermore, the production of lycopene, a widely-used carotenoid, was also increased. Taken together, our research helps to deepen the understanding of the salt tolerance mechanism of R. palustris and also widens the application of R. palustris in highly-saline environments.

Development of lycopene-based whole-cell biosensors for the visual detection of trace explosives and heavy metals.

Residual explosives in conflicting zones have caused irreversible damage to human safety and the environment. Whole-cell biosensors can to detect remnants of buried explosives, such as 2,4-dinitrotoluene (DNT), a stable and highly volatile compound in explosives. However, all the reported whole-cell biosensors utilize fluorescence or luminescence as the biological markers, making their detection difficult in real minefields. Here, we presented a lycopene-based whole-cell biosensor in Escherichia coli to output visible signals in response to DNT, which can help in the visual detection of buried explosives. To construct the whole-cell biosensor, the DNT-responsive promoter yqjF was used as the sensing element, and the lycopene synthetic gene cassette crtEBI was served as the reporting element. Then, the metabolic flux for lycopene production was enhanced to improve the output signal of the whole-cell biosensor, and a terminator was utilized to reduce the background interference. The optimized biosensor LSZ05 could perceive at least 1 mg/L DNT. The DNT-specificity and robust performance of the biosensor under different environmental factors were confirmed. Our results showed that converting the biosensor into a lyophilized powder was an effective storage method. The biosensor LSZ05 could effectively detect DNT in two kinds of soil samples. The lycopene-based whole-cell biosensor could also be used to visually detect heavy metals. Our findings laid the foundation for visually detecting buried explosives in minefields, which was a valuable supplement to the reported biosensors. The methods used for optimizing the lycopene-based whole-cell biosensor, including the improvement of the output signal and reduction of background interference, were quite effective.

Optimization of IspSib stability through directed evolution to improve isoprene production.

Enzyme stability is often a limiting factor in the microbial production of high-value-added chemicals and commercial enzymes. A previous study by our research group revealed that the unstable isoprene synthase from Ipomoea batatas (IspSib) critically limits isoprene production in engineered Escherichia coli. Directed evolution was, therefore, performed in the present study to improve the thermostability of IspSib. First, a tripartite protein folding system designated as lac'-IspSib-'lac, which could couple the stability of IspSib to antibiotic ampicillin resistance, was successfully constructed for the high-throughput screening of variants. Directed evolution of IspSib was then performed through two rounds of random mutation and site-saturation mutation, which produced three variants with higher stability: IspSibN397V A476V, IspSibN397V A476T, and IspSibN397V A476C. The subsequent in vitro thermostability test confirmed the increased protein stability. The melting temperatures of the screened variants IspSibN397V A476V, IspSibN397V A476T, and IspSibN397V A476C were 45.1 ± 0.9°C, 46.1 ± 0.7°C, and 47.2 ± 0.3°C, respectively, each of which was higher than the melting temperature of wild-type IspSib (41.5 ± 0.4°C). The production of isoprene at the shake-flask fermentation level was increased by 1.94-folds, to 1,335 mg/L, when using IspSibN397V A476T. These findings provide insights into the optimization of the thermostability of terpene synthases, which are key enzymes for isoprenoid production in engineered microorganisms. In addition, the present study would serve as a successful example of improving enzyme stability without requiring detailed structural information or catalytic reaction mechanisms.IMPORTANCEThe poor thermostability of IspSib critically limits isoprene production in engineered Escherichia coli. A tripartite protein folding system designated as lac'-IspSib-'lac, which could couple the stability of IspSib to antibiotic ampicillin resistance, was successfully constructed for the first time. In order to improve the enzyme stability of IspSib, the directed evolution of IspSib was performed through error-PCR, and high-throughput screening was realized using the lac'-IspSib-'lac system. Three positive variants with increased thermostability were obtained. The thermostability test and the melting temperature analysis confirmed the increased stability of the enzyme. The production of isoprene was increased by 1.94-folds, to 1,335 mg/L, using IspSibN397V A476T. The directed evolution process reported here is also applicable to other terpene synthases key to isoprenoid production.

Co-biosynthesis of germacrene A, a precursor of ß-elemene, and lycopene in engineered Escherichia coli.

ß-Elemene is the major component of a traditional Chinese medicine (Rhizoma Curcumae) for cancer treatment, and plant extraction is the major methods currently. Biosynthesis of ß-elemene is a promising and attractive route due to its advantages, including environmentally friendly processes, renewable resources, and sustainable development. In this research, biosynthesis of germacrene A, direct precursor of ß-elemene, in Escherichia coli was successfully performed and 11.99 mg/L germacrene A was obtained. Thereafter, a cobiosynthesis system for germacrene A and lycopene, another kind of isoprenoid, was constructed. Furthermore, the cultivation conditions were optimized. The germacrene A production was increased to the highest level reported to date, 364.26 mg/L, threefold increase to the strain with only germacrene A production. The cobiosynthesis system was suggested to promote the metabolic flux for germacrene A production. This research enabled germacrene A production in E. coli, and it highlights the promoting mechanism of the cobiosynthesis system for two chemicals which are both belonging to isoprenoids. KEY POINTS : • Co-production of germacrene A and lycopene in E. coli. • Promoting mechanism of cobiosynthesis of two isoprenoid compounds in E. coli. • Shake-flask production of germacrene A reached to the highest 364.26 mg/L in E. coli.

Efficacy and safety of yinqiao powder combined with western medicine in the treatment of pneumonia: A systematic review and meta-analysis.

OBJECTIVE: This review aimed at systematically evaluating the efficacy and safety of Yinqiao powder combined with western medicine in the treatment of pneumonia. METHODS: A systematic search for randomized controlled trials (RCTs) focusing on pneumonia treatment using a combination of Yinqiao powder and western medicine was performed in PubMed, the Cochrane Library, EMBASE, Web of Science, CNKI, Wanfang, Weipu (VIP) and CBM. The retrieval time limit was from the establishment of the database to June 2020. Two researchers independently screened the literature, extracted the data and evaluated the bias risk of the included studies. A meta-analysis was performed using RevMan5.3 software. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULT: Fifteen RCTs involving 1705 patients were included in the analysis. The meta-analysis results revealed the total effective rate of the treatment group [RR = 1.21, 95% CI (1.15, 1.27), P < 0.00001], bacterial clearance rate [RR = 1.13, 95% CI (1.05, 1.22), P = 0.001], adverse reactions [RR = 0.54, 95% CI (0.38, 0.76), P = 0.0005]. There were statistically significant differences in the cooling time, T cell number, procalcitonin (PCT) and C-reactive protein (CRP) value decline rate (P < 0.05). There was no statistically significant difference in the decline rate of neutrophils and leukocytes (P > 0.05). CONCLUSION: The current evidence indicated that the Yinqiao powder combined with western medicine can improve total efficiency in the treatment of pneumonia patients. The combination therapy performed better when compared to western medicine alone in the cooling time, bacterial clearance rate, T cell count, decline rates of CRP and PCT as well as in the incidences of adverse reactions. However, there was no significant difference in the decline rates of neutrophils and leucocytes between the two groups. The funnel plot, Egger's test and Begg's test indicated publication bias, which may be associated with unpublished negative study results. Due to the limitation of the quality and quantity of the included studies, more high-quality studies should be performed to verify our conclusions.

SOX11 inhibits tumor proliferation and promotes cell adhesion mediated-drug resistance via a CD43 dependent manner in mantle cell lymphoma.

SOX11 is a critical biomarker for mantle cell lymphoma (MCL) diagnosis; however, its role remains unclear in MCL. Here, clinical-pathological analysis showed Ki67 index was negatively relevant to SOX11 expression only in CD43 positive cases. Coexpression of SOX11/CD43 indicated longer overall survival. In vitro, knockout/overexpression of SOX11 or CD43 promoted/inhibited cell proliferation respectively. CD43 overexpression reversed tumor proliferation induced by SOX11 knockdown. Furthermore, overexpressing/silencing the SOX11/CD43 gene affects phosphorylation of p38-MAPK while p38 inhibitor reversed proliferation induced by si-SOX11 or si-CD43, respectively. In CAM-DR model, both SOX11 and CD43 in MCL cells were elevated when co-cultured with M2-10B4 bone marrow fibroblasts or fibronectin. Knockdown/overexpression of SOX11 decreased/increased cell adhesion, respectively, and the effect induced by silencing SOX11 was reversed by overexpression of CD43. Collectively, SOX11 could inhibit tumor proliferation and promote CAM-DR in a CD43 dependent manner.

Foam Cell-Derived CXCL14 Muti-Functionally Promotes Atherogenesis and Is a Potent Therapeutic Target in Atherosclerosis.

CXC chemokine family has been related to atherogenesis for long. However, the relationship between CXCL14 and atherogenesis is still unclear. This study preliminarily detected CXCL14 expression at foam cells in atherosclerosis specimens by immunohistochemistry. In vitro foam cells were derived from THP-1 after phorbol-12-myristate-13-acetate (PMA) and oxidized low-density lipoprotein (ox-LDL) stimulation. Immunoblotting and qPCR convinced CXCL14 expression variation during foam cell formation. We further demonstrated that ox-LDL regulated CXCL14 expression by AP-1. AP-1 could bind to CXCL14 promoter and up-regulate CXCL14 mRNA expression. Besides, CXCL14 promoted THP-1 migration, macrophage lipid phagocytosis, and smooth muscle cell migration as well as proliferation mainly via the ERK1/2 pathway. Additionally, a CXCL14 peptide-induced immune therapy showed efficacy in ApoE-/- mouse model. In conclusion, our study demonstrated that CXCL14 is highly up-regulated during foam cell formation and promotes atherogenesis in various ways. CXCL14 may be a potent therapeutic target for atherosclerosis.

Knockdown of FOXO3a induces epithelial-mesenchymal transition and promotes metastasis of pancreatic ductal adenocarcinoma by activation of the ß-catenin/TCF4 pathway through SPRY2.

BACKGROUND: Early invasion and metastasis are responsible for the dismal prognosis of pancreatic ductal adenocarcinoma (PDAC), and epithelial-to-mesenchymal transition (EMT) is recognized as a crucial biological progress in driving tumor invasion and metastasis. The transcription factor FOXO3a is inactivated in various types of solid cancers and the loss of FOXO3a is associated with EMT and tumor metastasis. In this study, we sought to explore whether SPRY2, a regulator of receptor tyrosine kinase (RTK) signaling, is involved in FOXO3a-mediated EMT and metastasis in PDAC. METHODS: Immunohistochemistry was performed in 130 paired PDAC tissues and paracarcinomatous pancreatic tissues. Cell proliferation and apoptosis were assessed by cell counting kit and flow cytometry, while cell migration and invasion were evaluated with wound healing and transwell assays. The changes in mRNA and protein levels were estimated by qRT-PCR and western blot. BALB/c nude mice xenograft model was established to evaluate tumorigenesis and metastasis in vivo. RESULTS: FOXO3a expression was remarkably reduced in PDAC tissues, and correlated with metastasis-associated clinicopathologic characteristics and poor prognosis in patients with PDAC. In addition to the promotion of proliferation and suppression of apoptosis, knockdown of FOXO3a or SPRY2 induced EMT and promoted the migration and invasion of PDAC cells via activation of the ß-catenin/TCF4 pathway. Moreover, silencing of SPRY2 reversed the suppressor effects induced by FOXO3a overexpression on EMT-associated migration and invasion of PDAC cells, while blockade of ß-catenin reversed the effects of SPRY2 loss. FOXO3a knockdown decreased SPRY2 protein stability, whereas SPRY2 knockdown enhanced ß-catenin protein stability. In vivo, FOXO3a knockdown promoted the tumorigenic ability and metastasis of PDAC cells. CONCLUSIONS: Our study suggests that knockdown of FOXO3a induces EMT and promotes metastasis of PDAC by activation of the ß-catenin/TCF4 pathway through SPRY2. Thus, FOXO3a may represent a candidate therapeutic target in PDAC.