Incentive strategy of dual innovation balance in green manufacturing innovation ecosystem: Based on hierarchical structure of innovation subject.

Exploratory innovation is a pivotal way to seize future opportunities in green manufacturing innovation ecosystems, and exploitative innovation is conducive to expanding existing markets and resources, so it is essential to discuss the balanced incentive strategy of dual innovation for the sustainable development of ecosystems. Based on the hierarchical structure, this paper divides the core subjects in the green manufacturing innovation ecosystem into the application layer, the support layer, and the scientific research layer, constructs the differential game model of the no-incentive scenario, the cost-sharing scenario, and the collaborative scenario, and discusses the incentive strategies of the three types of subjects and the ecosystem in the evolution process of the dual innovation balance. The conclusions are as follows: (1) The level of dual innovation balance effort of the three types of subjects decreases with the increase of resource costs and environmental construction costs and increases with the increase of innovation balance capacity; (2) Cost sharing from the application layer to the support layer and the scientific research layer can enhance the effort level of both, which in turn enhances the optimal benefits for the three types of subjects and the ecosystem as a whole; (3) In the collaborative scenario, the level of effort and total ecosystem benefits of the innovation balance of the three types of subjects are strictly better than in the no incentive scenario, and the Pareto-optimality of the three subjects and the ecosystem will be realized after the coefficients of the distribution of benefits among the three types of subjects are determined. Based on this, this paper puts forward specific suggestions for the optimization of the structural relationship of the innovation body hierarchy, the exploitation of green manufacturing resources, and the macro-planning of the management department.

Biosynthesized gold nanoparticles that activate Toll-like receptors and elicit localized light-converting hyperthermia for pleiotropic tumor immunoregulation.

Manipulating the tumor immune contexture towards a more active state can result in better therapeutic outcomes. Here we describe an easily accessible bacterial biomineralization-generated immunomodulator, which we name Ausome (Au + [exo]some). Ausome comprises a gold nanoparticle core covered by bacterial components; the former affords an inducible hyperthermia effect, while the latter mobilizes diverse immune responses. Multiple pattern recognition receptors actively participate in Ausome-initiated immune responses, which lead to the release of a broad spectrum of pro-inflammatory cytokines and the activation of effector immune cells. Upon laser irradiation, tumor-accumulated Ausome elicits a hyperthermic response, which improves tissue blood perfusion and contributes to enhanced infiltration of immunostimulatory modules, including cytokines and effector lymphocytes. This immune-modulating strategy mediated by Ausome ultimately brings about a comprehensive immune reaction and selectively amplifies the effects of local antitumor immunity, enhancing the efficacy of well-established chemo- or immuno-therapies in preclinical cancer models in female mice.

Targeting CXCR1 alleviates hyperoxia-induced lung injury through promoting glutamine metabolism.

Although increasing evidence suggests potential iatrogenic injury from supplemental oxygen therapy, significant exposure to hyperoxia in critically ill patients is inevitable. This study shows that hyperoxia causes lung injury in a time- and dose-dependent manner. In addition, prolonged inspiration of oxygen at concentrations higher than 80% is found to cause redox imbalance and impair alveolar microvascular structure. Knockout of C-X-C motif chemokine receptor 1 (Cxcr1) inhibits the release of reactive oxygen species (ROS) from neutrophils and synergistically enhances the ability of endothelial cells to eliminate ROS. We also combine transcriptome, proteome, and metabolome analysis and find that CXCR1 knockdown promotes glutamine metabolism and leads to reduced glutathione by upregulating the expression of malic enzyme 1. This preclinical evidence suggests that a conservative oxygen strategy should be recommended and indicates that targeting CXCR1 has the potential to restore redox homeostasis by reducing oxygen toxicity when inspiratory hyperoxia treatment is necessary.

Tea consumption during the periconceptional period does not significantly increase the prevalence of neural tube defects: A systematic review and dose-response meta-analysis.

Tea consumption may potentially promote the prevalence of neural tube defects (NTDs) because catechins, the main components of tea polyphenols, can lead to the depletion of bioavailable folate. Many epidemiologic studies have explored the association between tea consumption and NTD risk; however, the findings are inconsistent. This systematic review and meta-analysis investigated the association between tea consumption and NTD. We hypothesized that tea consumption during the periconceptional period would significantly promote NTD prevalence. Three electronic databases (PubMed, Web of Science, and Embase) were searched from their inception through July 14, 2021. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were obtained using random-effects models. Subgroup analyses were performed to explore potential confounders. In addition, a dose-response analysis was conducted to examine further the association between tea consumption and NTD. Seven articles with nine studies yielded 2834 cases and 19,924 participants. The results showed that tea consumption during the periconceptional period did not significantly increase NTD prevalence (OR, 1.37; 95% CI, 0.96-1.95; P = .08). This finding was consistent with the evaluation of 3 subtypes of NTDs: anencephaly (OR, 1.36; 95% CI, 0.84-2.20; P = .22), spina bifida (OR, 1.51; 95% CI, 0.84-2.72; P = .17), and encephalocele (OR, 0.99; 95% CI, 0.46-2.15; P = .98). Furthermore, a significant dose-response association between tea consumption and the risk of NTDs was not evident (P > .05). Our meta-analysis suggests that maternal tea consumption during the periconceptional period did not significantly increase the prevalence of NTDs. Further studies are needed to ascertain the association between tea consumption and NTD prevalence.

The determination of monosaccharide in different years Qingzhuan Dark Tea polysaccharide by liquid chromatography-mass spectrometry.

AIM: To establish a fast, sensitive and accurate high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for determining the monosaccharide content of Qingzhuan Dark Tea polysaccharides in different years (2 years, 5 years and 11 years). METHODS: The optimised chromatographic conditions were achieved on a C18 column (5.0 µm, 250 mm × 4.6 mm inner diameter). The mobile phase flow rate was 0.9 mL/min and the column temperature was set to 27°C. The aqueous phase A (5 mM aqueous ammonium acetate) and organic phase B (acetonitrile) were used to elute the target analyses isocratically (0-60 min: 18% B). The mass spectrometer detector was equipped with an electron spray ionisation (ESI)source, and multiple reaction monitoring (MRM) mode was used for the determination of 1-phenyl-3-methyl-5-pyrazolone (PMP) derived monosaccharides. RESULTS: We carried out a comprehensive methodological validation of PMP derived monosaccharides, including linearity, precision, stability and repeatability. Nine monosaccharides (rhamnose, mannose, ribose, glucose, galacturonic acid, xylose, galactose, fucose and arabinose) of Qingzhuan Dark Tea polysaccharides were identified, in which ribose and fucose were reported for the first time. The results showed the contents of these nine monosaccharides differed significantly among different years. CONCLUSIONS: The validated method is reliable, accurate, repeatable and can be applied to quality assessment of these monosaccharides.

META analysis on the effect of taijiquan on improving negative psychological symptoms of college students and the optimal dose.

Background: Taijiquan, as a physical and mental exercise, can improve the negative psychology of college students. However, it is still controversial, and the optimal exercise dose of taijiquan to interfere with negative psychology has not been evaluated. Objective: This study is aimed at systematically evaluating the effect of taijiquan therapy on improving negative psychological symptoms of college students and its optimal intervention dose. Methods: Search databases such as Web of Science, Embase, PubMed, CNKI, WFSD, etc. Collect high-quality relevant RCT studies. After screening, extracting, coding and counting the data, a META analysis is done through Review Manage 5.3 and Stata 15.0 software. PICOS established the eligibility criteria to select the studies as follows: (i) population - non-clinical of college students; (ii) intervention - taijiquan intervention; (iii) comparison - taijiquan intervention group and regular physical activity group; (iv) outcomes - depression, anxiety; and (v) study design - randomized controlled trial. Results: A total of 12 articles and 1,000 samples were included. All of the participants are college students. Taijiquan therapy can significantly reduce the depression and anxiety symptoms of college students [SMD = -0.53, 95% CI (-0.82, -0.23)], [SMD = -0.49, 95% CI (-0.90, -0.09)], with statistical significance (P < 0.05). Subgroup analysis shows that: there is a precise focus on depression and anxiety symptoms. The intervention period is more than 12 weeks, and the best effect appears when people practice 3 times a week. The best single intervention time for depression symptoms is 60 min, and for anxiety symptoms 80-90 min. It is found that taijiquan combined with mindfulness intervention can significantly reduce negative psychological symptoms like depression and anxiety of college students than single taijiquan intervention. Funnel plot combined with sensitivity analysis, Begg, Egger test showed no publication bias. Conclusion: Taijiquan intervention can effectively improve the negative psychological symptoms of college students, and it has great promotion value in colleges and universities. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022314071.

New-onset depression after hip fracture surgery among older patients: Effects on associated clinical outcomes and what can we do?

BACKGROUND: Hip fracture in the elderly is a worldwide medical problem. New-onset depression after hip fracture has also received attention because of its increasing incidence and negative impact on recovery. AIM: To provide a synthesis of the literature addressing two very important questions arising from postoperative hip fracture depression (PHFD) research: the risk factors and associated clinical outcomes of PHFD, and the optimal options for intervention in PHFD. METHODS: We searched the PubMed, Web of Science, EMBASE, and PsycINFO databases for English papers published from 2000 to 2021. RESULTS: Our results showed that PHFD may result in poor clinical outcomes, such as poor physical function and more medical support. In addition, the risk factors for PHFD were summarized, which made it possible to assess patients preoperatively. Moreover, our work preliminarily suggested that comprehensive care may be the optimal treatment option for PHFDs, while interdisciplinary intervention can also be clinically useful. CONCLUSION: We suggest that clinicians should assess risk factors for PHFDs preoperatively, and future research should further validate current treatment methods in more countries and regions and explore more advanced solutions.

Genome-wide analysis of the SBP-box gene family transcription factors and their responses to abiotic stresses in tea (Camellia sinensis).

SQUAMOSA promoter-binding protein (SBP)-box gene family is one kind of plant-specific transcription factor that plays important roles in the process of resisting abiotic stress. The SBP-box gene family has been studied in many species, but their functions are not yet clear in Camellia sinensis var. sinensis (CSS) (tea) plants. In our study, 25 SBP-box genes in the CSS were identified in the reference genome and classified into six groups based on a phylogenetic tree. The expression pattern of CsSBP genes under temperature stresses showed that CsSBPs were involved in the process of resisting temperature stresses. CsSBP8 had a positive effect on the anthocyanin accumulation during high temperature exposures, but CsSBP12 has a high correlation with anthocyanin accumulation during both high and low temperature. This study provides a foundation for the further study of CsSBP genes involved in the anthocyanin biosynthesis pathway during the temperature stress in tea.

Chinese Herbal Formula Ermiao Powder () Regulates Cholinergic Anti-inflammatory Pathway in Rats with Rheumatoid Arthritis / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of Chinese herbal formula Ermiao Powder (, EMP) on the expression of cholinergic anti-inflammatory pathway in rats with rheumatoid arthritis (RA).@*METHODS@#Seventy-two rats were randomly divided into 6 groups according to body weight, including normal control group, collageninduced arthritis (CIA) group, three doses EMP groups, and methotrexate (MTX) group (n=12 per group). All of the rats except for those in the normal control group were given multipoint subcutaneous injection of bovine type II collagen to establish a CIA model. Three EMP groups received a high- (4.5 g/kg), medium- (3.0 g/kg), and low- (1.5 g/kg) doses of EMP by intragavage, respectively. MTX group was injected intraperitoneally MTX at 0.9 mg/kg once a week as the positive control. The administration was 3 consecutive weeks. Joint swelling, arthritis index, and body weight changes in different experimental groups of rats were tested. The joint damage was evaluated by masson staining. Quantitative real-time polymerase chain reaction, Western blot, and immunohistochemistry (IHC) were performed to evaluate the expression of CHRNA7, encoding α7 nicotinic acetylcholine receptor in the cholinergic anti-inflammatory pathway, in different tissues and their localization in the spleen and joints.@*RESULTS@#CHRNA7 expression levels were significantly higher in the joints and spleens of CIA group than those in normal control group (both P<0.05). Moreover, the CHRNA7 mRNA and protein levels in the spleen and joints of MTX and three doses of EMP groups were significantly lower than CIA group (all P<0.05). Compared with the MTX group, treatment with low-dose EMP resulted in significant reduction of CHRNA7 mRNA and protein expression levels (P<0.05 or P<0.01). IHC showed positive signals of CHRNA7 in the white pulp and red pulp of the spleens of rats; CHRNA7 was expressed on fibroblast-like synoviocytes, macrophages, and endothelial cells in the joints of rats, and the expression in the joints of low-dose EMP group was significantly lower than that in the CIA group (P<0.01).@*CONCLUSIONS@#Cholinergic anti-inflammatory pathway was involved in the generation of the inflammatory reaction in CIA rats, and EMP exerted therapeutic effect on RA through cholinergic anti-inflammatory pathway.

The effects of fluoride on neuronal function occurs via cytoskeleton damage and decreased signal transmission.

It has been reported that fluoride exposure may cause serious public health problems, particularly neurotoxicity. However, the underlying mechanisms remain unclear. This study used Neuro-2A cells to investigate the effects of fluoride on the cytoskeleton. The Neuro-2A cells were exposed to 0, 1, 2, 4 and 6 mM sodium fluoride (NaF) for 24 h. Cell viability and lactate dehydrogenase (LDH) release were examined. It was observed that exposure to NaF reduced cell viability, disrupted cellular membrane integrity, and high levels of LDH were released. The observed changes occurred in a dose response manner. Morphologic observations showed that cell became rounded and were loosely adherent following exposure to NaF. Axon spines and normal features disappeared with high dose NaF treatment. The expression of MAP2 and synaptophysin decreased, particularly at 4 mM and 6 mM (P < 0.05) for MAP2. These results corroborate the morphologic observations. The content of glutamate and NMDAR (glutamate receptor) protein were assessed to help understand the relationship between synapses and neurotransmitter release using ELISA and Western-blot. Compared with the control, glutamate and NMDAR expression declined significantly at 4 mM and 6 mM (P < 0.05) group. Finally, the ultrastructural changes observed with increasing doses of NaF were: disappearance of synapses, mitochondrial agglutination, vacuole formation, and cellular edema. Taken together, NaF exposure disrupted cellular integrity and suppressed the release of neurotransmitters, thus effecting neuronal function. These findings provide deeper insights into roles of NaF in neuron damage, which could contribute to a better understanding of fluoride-induced neurotoxicity.

[Reversion Mechanism Study of PESV to Multidrug Resistance at Leukemia Stem Cell Level].

OBJECTIVE: To explore the effect of peptide extract from scorpion venom (PESV) to multidrug resistance (MDR) of leukemic stem cell (LSC) in vivo. METHODS: K562/A02 cells were cultured and collected in the logarithmic phase. K562/A02 stem cells were screened using immunomagnetic beads for reserve. K562/A02 LSC was injected to 5 of 40 BABL/c nude mice for preparing subcutaneous tumor. The rest 35 nude mice were then randomly divided into 7 groups, i.e., the normal control group, the model group, the Adriamycin (ADM) group, the PESV group, the ADM +high dose PESV group, the ADM + middle dose PESV group, the ADM +low dose PESV group, 5 in each group. Tumor tissue was embedded in all groups except the normal control group. One milliliter normal saline was peritoneally injected to mice in the model group after modeling, once per day. ADM 0. 05 mg was peritoneally injected to mice in the ADM group, once per other day. PESV 2 µg was peritoneally injected to mice in the PESV group, once per day. Mice in 3 ADM + PESV groups were peritoneally injected with ADM 0. 05 mg (once per other day) plus PESV (5, 2, and 1 µg respectively, once per day). All medication lasted for 14 days. P-glycoprotein (P-gp) was detected using flow cytometry. Breast cancer resistance protein (BCRP) and mRNA expression of multidrug resistance 1 (MDR1) were measured using RT-PCR. Aldehyde dehydrogenase 1 (ALDH1) was detected using immunohistochemistry. Phosphoinositide 3-kinase (PI3K) was detected using Western blot. NF-κB content was detected using ELISA. RESULTS: CD34 + CD38-ratio was 31.5% and IC50 was (60.33 ± 10. 68) µg/mL before K562/A02 cells were screened with immunomagnetic beads, while they were 92. 8% and (58. 33 ±9. 72) µg/mL after screen. The tumor formation rate was 100% in modeling mice. Compared with the model group, no statistical difference of each index occurred in the ADM group (P <0. 05). There was statistical difference in BCRP, MDR1 mRNA, or NF-κB factor between the model group and the PESV group (P <0. 05). The expression level of P-gp obviously decreased and the protein expression of P13K was down-regulated in 3 ADM + PESV groups (P <0. 05); mRNA expression of BCRP decreased and mRNA ex- pression of MDR1 obviously increased in the ADM + high dose PESV group and the ADM + middle dose PESV group, with statistical difference (P <0. 05). Protein expression of P13K was down-regulated in the ADM+ high dose PESV group, with statistical difference (P <0. 05). P-gp value, BCRP mRNA expression, MDR1 mRNA expression, PI3K, and NF-κB factor were all obviously down-regulated in the ADM +high dose PESV group, as compared with the ADM group and the PESV group respectively (P <0. 05). There was no statistical difference in ALDH1 positive rate among all groups (P >0. 05). Conclusion PESV combined ADM could down-regulate expression levels of P-gp, BCRP, MDR1, P13K, and NF-κB, strengthen the sensitivity of K562/A02 LSC to ADM in vivo, and reverse MDR of LSC.

Whole-genome bisulfite sequencing of multiple individuals reveals complementary roles of promoter and gene body methylation in transcriptional regulation.

BACKGROUND: DNA methylation is an important type of epigenetic modification involved in gene regulation. Although strong DNA methylation at promoters is widely recognized to be associated with transcriptional repression, many aspects of DNA methylation remain not fully understood, including the quantitative relationships between DNA methylation and expression levels, and the individual roles of promoter and gene body methylation. RESULTS: Here we present an integrated analysis of whole-genome bisulfite sequencing and RNA sequencing data from human samples and cell lines. We find that while promoter methylation inversely correlates with gene expression as generally observed, the repressive effect is clear only on genes with a very high DNA methylation level. By means of statistical modeling, we find that DNA methylation is indicative of the expression class of a gene in general, but gene body methylation is a better indicator than promoter methylation. These findings are general in that a model constructed from a sample or cell line could accurately fit the unseen data from another. We further find that promoter and gene body methylation have minimal redundancy, and either one is sufficient to signify low expression. Finally, we obtain increased modeling power by integrating histone modification data with the DNA methylation data, showing that neither type of information fully subsumes the other. CONCLUSION: Our results suggest that DNA methylation outside promoters also plays critical roles in gene regulation. Future studies on gene regulatory mechanisms and disease-associated differential methylation should pay more attention to DNA methylation at gene bodies and other non-promoter regions.

Improvement of L-lactic acid production by osmotic-tolerant mutant of Lactobacillus casei at high temperature.

L-Lactic acid production by Lactobacillus casei was used as a model to study the mechanism of substrate inhibition and the strategy for enhancing L-lactic acid production. It was found that the concentration of cell growth and L-lactate decreased with the increase of glucose concentration and fermentation temperature. To enhance the osmotic stress resistance of the strain at high temperature, a mutant G-03 was screened and selected with 360 g/L glucose at 45°C as the selective criterion. To further increase the cell growth for lactic acid production, 3 g/L of biotin was supplemented to the medium. As a result, L: -lactate concentration by the mutant G-03 reached 198.2 g/L (productivity of 5.5 g L(-1) h(-1)) at 41°C in a 7-L fermentor with 210 g/L glucose as carbon source. L: -Lactate concentration and productivity of mutant G-03 were 115.2% and 97.8% higher than those of the parent strain, respectively. The strategy for enhancing L: -lactic acid production by increasing osmotic stress resistance at high temperature may provide an alternative approach to enhance organic acid production with other strains.

[Comparision of different interventional therapies for primary liver cancer].

OBJECTIVE: To investigate the efficacy of different interventional therapies for primary hepatic cell cancer (HCC). METHODS: 1126 HCC patients before or after hepatectomy were treated by different kinds of interventional therapies: transcatheter arterial chemoembolization (TACE), TACE and radio-frequency ablation (RFA), Chinese traditional medicine and biotherapy after TACE or the transcatheter arterial infusion (TAI). The results of liver function, alpha-fetoprotein, imaging, color-ultrasonography and survival rate were reviewed. RESULTS: 874 patients were followed up for 2 to 63 months. The overall 1-, 3-, 5-year survival rate was 67.8% , 28.7% and 18.8%, respectively. The 1-, 3-, 5-year survival rate of patients who received TACE before hepatectomy was 74.7%, 41.4% and 36.9% ; after hepatectomy 78.9%, 40.4% and 37.5%, respectively. The response rate ( PR + NC) of TACE and RFA was 93.4%, and the 1-, 3-year survival rate was 74.5% and 36.8%, respectively, after TACE and RFA. The response rate (PR + NC) of TACE was 83.2% with 1-, 3-, 5-year survival rate of 69.3%, 21.7%, 8.4% after TACE, respectively. The response rate (PR + NC) of TAI was 27.5% with 1-, 2-year survival rate of 11. 6% and 0 after TAI. The Child grade of liver function, color-ultrasonography and alpha-fetoprotein of TACE + RFA group, TACE and TAI were compared. There was no significant difference between each above mentioned index among TACE, RFA or TACE groups. CONCLUSION: Compared with other modalities, transcatheter arterial chemoembolization (TACE) before or after hepatectomy is more effective than other interventional therapies for primary hepatocellular cancer, whereas, if combined with radiofrequency ablation (TAI), it is much more effective than TACE alone.

Impact of myocardial ischemia and reperfusion on ventricular defibrillation patterns, energy requirements, and detection of recovery.

BACKGROUND: Shocks that have defibrillated spontaneous ventricular fibrillation (VF) during acute ischemia or reperfusion may seem to have failed if VF recurs before the ECG amplifier recovers after shock. This could explain why the defibrillation threshold (DFT) for spontaneous VF appears markedly higher than for electrically induced VF. METHODS AND RESULTS: The DFT for electrically induced VF (E-DFT) was determined in 15 pigs before ischemia, followed by left anterior ascending or left circumflex artery occlusion. VF was electrically induced 20 minutes after occlusion, followed 5 minutes later by reperfusion. Whether spontaneous or electrically induced, VF during occlusion or reperfusion was treated with up to 3 shocks at 1.5xE-DFT. If all 3 shocks failed, shock strength was increased. Thirty minutes after reperfusion, the other artery was occluded and the protocol was repeated. Defibrillation was considered successful if postshock sinus/idioventricular rhythm was present for > or = 30 seconds. VF recurring within 30 seconds after the shock was considered immediate or delayed if the first postshock activation complex in a rapidly restored ECG recording was VF or sinus/idioventricular rhythm, respectively. Defibrillation efficacy at 1.5xE-DFT was significantly higher for electrically induced ischemic VF (76%) than for spontaneous VF (31%). The incidence of delayed recurrence after electrically induced nonischemic (3%) or ischemic (20%) VF was significantly lower than after spontaneous VF (75%). Mean VF recurrence time after spontaneous VF was 4.6+/-5.3 seconds. CONCLUSIONS: Spontaneous VF can be halted by a shock but then quickly restart before a standard ECG amplifier has recovered from postshock saturation, making it appear that the shock failed.