Search

Chirality manipulation in supramolecules, especially in multicomponent supramolecular structures, is crucially desired. Herein, we report a feasible approach to achieve the chirality transfer, amplification, and inversion in a ternary supramolecular system consisting of new chiral molecules L4, which contain two positively charged viologen units and express an R configuration, cucurbit[8]uril (CB[8]) molecules, and surfactant molecules sodium dodecyl sulfate (SDS). A series of experimental techniques and measurements were used to investigate the mechanism of chirality changes, including circular dichroism (CD) spectroscopy, absorption spectroscopy, isothermal titration calorimetry (ITC), and small-angle X-ray scattering (SAXS). The achiral SDS molecules were found to facilitate the transformation of chirality from the molecular level to the supramolecular level. The CD signals could be regulated precisely as the coassembled ternary supramolecular structure of the L4/SDS/CB[8] system strongly depended on the quantity of each component. When the molar ratio of L4, SDS, and CB[8] reached 3 : 2 : 2, a significant chirality inversion from the positive upward CD signals to the negative downward CD signals was observed. The combination effects of non-covalent interactions which involve electrostatic and host–guest interactions caused a supramolecular structure packing change from the lamellar to the rectangular stacking pattern and resulted in a large chirality inversion at the supramolecular level. Our results may provide a facile approach to regulate multiple chiral activities in multicomponent supramolecular systems.

Polyethylene glycol (PEG)-conjugated lipid significantly contributed to the success of three approved lipid nanoparticles (LNP)-delivered therapeutics, including two COVID-19 mRNA vaccines. With the large-scale vaccination of mRNA vaccines, it has become an imminent task to elucidate the possible PEG-associated immune responses induced by clinically relevant LNP. Up to date there are only four small-scale population-based studies emphasizing the changes of PEG-specific antibodies upon injection of mRNA vaccines. However, inconsistent data were obtained due to significant person-to-person and study-to-study variabilities. To clarify the PEG-associated immune responses triggered by clinically relevant LNP in a model system with least “noise”, we initiated an animal study using the PEGylated LNP of BNT162b2 (with the largest number of recipients) as a representative LNP and simulated the clinical practice. Through designing a series of time points and three doses correlated with the PEG exposure amount contained in three approved LNP-based drugs, we demonstrated for the first time that generation and changes of anti-PEG IgM and IgG were time- and dose-dependent. Unexpectedly, we found that unlike other thymus-independent antigens (TI-Ag), PEGylated LNP not only induced isotype switch and production of anti-PEG IgG, but caused immune memory, leading to rapid enhancement and longer lasting time of both anti-PEG IgM and IgG upon repeated injection. Importantly, pharmacokinetic studies discovered that initial injection of PEGylated LNP accelerated the blood clearance of subsequently injected LNP. These findings refine our understandings on PEGylated LNP and possibly other PEG derivatives, and may lead to optimization of premarket guidelines and clinical practice of PEGylated LNP-delivered therapeutics.

The molecularly imprinted electrochemical aptasensor was constructed based on co-deposition of zinc oxide and gold nanoparticles/reduced graphene oxide composite. Aptamer was used as a new kind of functional monomer and the aptamer-amoxicillin complex was formed by hydrogen bond. Then, the complex was fixed on the surface of the modified electrode by Au-S bond. Three-dimensional imprinted polymeric membrane was formed by electropolymerization of dopamine, and the imprinted sites with good specificity and affinity were formed after elution. Combined with the specificity of molecularly imprinted technology and the affinity of aptamer, the selective recognition of amoxicillin can be realized. Under the optimal experimental conditions, the linear range was from 10

Lacking of S-wave velocity in logging will negatively affect the process of reservoir prediction and formation evaluation for organic rich rock reservoir. In this paper, a simple but effective method is presented to predict the S-wave velocity from P-wave velocity based on the combination of the critical porosity consolidation coefficient (CPCC) model with dual-variable parameters and quantum particle swarm optimization (QPSO) algorithm. In the presented method, the P-and S-wave velocities of organic-rich rock are linked by consolidation coefficient and critical porosity. Then, the error between the measured and calculated P-wave velocity is used to establish the inverse objective function. Moreover, the QPSO algorithm is introduced to invert the critical porosity and consolidation coefficient. Finally, the S-wave velocity can be predicted using the inverted parameters. Compared with two existing single-parameter adaptive methods, the predicted S-wave velocity of the proposed method is superior, which can be satisfactorily implemented for laboratory measurement and on logging data.

Economics has some limitations, such as insecure multiple parties economical investment decision and leakage of business quotation. Secret image sharing (SIS) for (k, n)-threshold is such a technique that protects an image through splitting it into n shadows, a.k.a. shadow images or shares, assigned to n corresponding participants. The secret image can be disclosed by obtaining k or more shadows. Polynomial-based SIS and visual secret sharing (VSS) are the chief research branches. This paper first analyzes the insecure issues in economics and then introduces two methods to apply typical SIS schemes to improve economical security. Finally, experiments are realized to illustrate the efficiency of the methods.

Conventional polymerizations mediated by living cells typically require synthetic transition-metal complexes or photoredox catalysts. Herein, we report an alternative photoinduced polymerization st...

Photoactivated trimerization of 2,3,3-trimethyl-3 H -indole derivatives created near infrared fluorophore Cy5. The synthetic method is air-tolerant, photosensitizer free, metal free, and condensation agent free. Living cells make Cy5 on a time scale of minutes under white light irradiation at a low power intensity, with the monomer as the only exogenous agent. The new method is promising to find applications in cell studies for in situ spatiotemporally controlled fluorescence imaging in living cells with low background signal.

Surface oxygen vacancy defects and metal deposition on semiconductor photocatalysts play a critical role in photocatalytic reactions. In this work, oxygen-deficient Bi2WO6 microspheres have been prepared by a facile ethylene glycol-assisted solvothermal method. Bi0 nanoparticles were reduced by in situ thermal-treatment on Bi2WO6 microspheres to obtain Bi0@Bi2WO6-x as well as maintaining the oxygen vacancies (OVs) under N2 atmosphere. Afterwards, photocatalytic NO oxidation removal activities of these photocatalysts were investigated under visible light irradiation and Bi0@Bi2WO6-x shows the best NO removal activity than other samples. The photogenerated charge separation and transfer are promoted by Bi0 nanoparticles deposited on the surface of semiconductor catalysts. OVs defects promote the activation of reactants (H2O and O2), thereby enhancing the formation of the active substance. Moreover, both OVs defects and Bi0 metal have the characteristics of extending light absorption and enhancing the efficient utilization of solar energy. Besides, the photocatalytic NO oxidation mechanism of Bi0@Bi2WO6-x was investigated by in situ FTIR spectroscopy for reaction intermediates and final products. This work furnishes insight into the synthesis strategy and the underlying photocatalytic mechanism of the surface-modified Bi0@Bi2WO6-x composite for pollutants removal.

To assess the value of three-dimensional volume contrast imaging C (VCI-C) combined with magnetic resonance imaging (MRI) in the diagnosis of fetal posterior cranial cavity disease.This study retrospectively analyzed the imaging data of 100 pregnant women with diagnosed abnormal development of fetal cerebellar vermis or posterior cranial fossa in our hospital from January 2020 to February 2022. VCI-C combined with MRI was used to evaluate the morphology of fetal cerebellar vermis, and the display of primary fissures and secondary fissures. The angle between the brain stem and cerebellar vermis (BVA) and the angle between brain stem and cerebellar tentorium (BTA) were measured and compared through MRI images.There was no significant difference between VCI-C and MRI in measuring the height, anteroposterior diameter, or area, BVA and BTA of fetal cerebellar vermis in the normal control group (P0.05). It can be considered that the two imaging methods are consistent in measuring the height, anteroposterior diameter and area, BVA, and BTA of the fetal cerebellar vermis in the normal control group. There was no significant difference between VCI-C and MRI in measuring the height, anterior posterior diameter and area, BVA, or BTA of the vermis in the group of fetal cerebellar vermis dysplasia (P0.05). The two imaging methods were comparable for all these measurements.Combining three-dimensional VCI-Cwith MRI diagnosis, the median sagittal section of the cerebellar vermis can be observed, the morphologic structure of the vermis, and the anatomical structure of the posterior cranial fossa can be reflected stereoscopically. Quantitative indexes can be measured and calculated to evaluate the developmental abnormalities of the fetal cerebellar vermis and the lesions of the posterior cranial fossa. Their combined effect is better than that of a single application.

Weedy rice (Oryza spp.), one of the most notorious weeds in rice fields, evades eradication through stem lodging and seed shattering. Many studies have focused on seed shattering in weedy rice. However, the lodging differentiation of weedy rice in different regions of China has not been characterized, and the underlying mechanisms of lodging difference between weedy rice and associated cultivated rice have not been studied in detail. Here, we compared the lodging variation among diverse Chinese weedy rice strains and between weedy rice and co-occurring cultivated rice. The chemical composition of basal stems was determined, and transcriptome and methylome sequencing were used to assess the expression variation of lodging-related genes. Results showed that the lodging degree varies between indica-derived weed strains with high lodging levels, which occurred predominantly in southern China, and japonica-derived strains with lower lodging levels found primarily in the north. The more lodging-prone indica weedy rice had a smaller bending stress and lower lignin content than non-lodging accessions. In comparison to co-occurring cultivated rice, the ratio of cellulose to lignin content in lodging-prone weedy rice was lower. DNA methylation variation of lignin synthesis-related OsSWN1, OsMYBX9, OsPAL1 and Os4CL3 mediated their expression level differnece and affected the ratio of cellulose to lignin content. Together, DNA methylation in lignin-related genes regulates stem strength and lodging variations in weedy rice, and between weed strains and their co-occurring cultivated rice.

The quest for rejuvenation and prolonged lifespan through transfusion of young blood has been studied for decades with the hope of unlocking the mystery of the key substance(s) that exists in the circulating blood of juvenile organisms. However, a pivotal mediator has yet been identified. Here, atypical findings are presented that are observed in a knockin mouse model carrying a lysine to arginine substitution at residue 74 of Krüppel-like factor 1 (KLF1/EKLF), the SUMOylation-deficient Klf1

3D bioprinting offers a powerful tool to fabricate vessel channels in tissue engineering applications, but inadequate strength of the vascular walls limited the development of this strategy and reinforced channels were highly desired for vascular constructions. Herein, we demonstrated a dual cross-linking system for 3D bioprinting of tubular structures, achieved by a combination of photo-cross-linking and enzymatic cross-linking. Photo-cross-linking of gelatin methacryloyl (GelMA) was achieved with a photoactive conjugated polymer PBF under 550 nm irradiation. Enzymatic cross-linking utilized cascade reactions catalyzed by glucose peroxidase and horseradish peroxidase that can cross-link both methacrylate and tyrosine moieties of GelMA. After removing the 3D-printed sacrificial layer (Pluronic F-127), the obtained perfusable channels showed great biocompatibility that allowed endothelial cells to adhere and proliferate. Our dual cross-linking strategy has great potential in 3D bioprinting of tubular structure for biomedical applications, especially for artificial blood vessels.

Background Numerous reports on microRNAs have illustrated their role in tumor growth and metastasis. Recently, a new prognostic factor, miR‐125b‐2‐3p, has been identified for predicting chemotherapeutic sensitivity in advanced colorectal cancer (CRC). However, the specific mechanisms and biological functions of miR‐125b‐2‐3p in advanced CRC under chemotherapy have yet to be elucidated. Methods MiR‐125b‐2‐3p expression was detected by real‐time PCR (RT‐PCR) in CRC tissues. The effects of miR‐125b‐2‐3p on the growth, metastasis, and drug sensitivity of CRC cells were tested in vitro and in vivo. Based on multiple databases, the upstream competitive endogenous RNAs (ceRNAs) and the downstream genes for miR‐125b‐2‐3p were predicted by bioinformatic analysis, followed by the experiments including luciferase reporter assays, western blot assays, and so on. Results MiR‐125b‐2‐3p was significantly lowly expressed in the tissues and cell lines of CRC. Higher expression of miR‐125b‐2‐3p was associated with relatively lower proliferation rates and fewer metastases. Moreover, overexpressed miR‐125b‐2‐3p remarkably improved chemotherapeutic sensitivity of CRC in vivo and in vitro. Mechanistically, miR‐125b‐2‐3p was absorbed by long noncoding RNA (lncRNA) XIST regulating WEE1 G2 checkpoint kinase (WEE1) expression. The upregulation of miR‐125b‐2‐3p inhibited the proliferation and epithelial‐mesenchymal transition (EMT) of CRC induced by lncRNA XIST. Conclusions Lower miR‐125b‐2‐3p expression resulted in lower sensitivity of CRC to chemotherapy and was correlated with poorer survival of CRC patients. LncRNA XIST promoted CRC metastasis acting as a ceRNA for miR‐125b‐2‐3p to mediate WEE1 expression. LncRNA XIST‐miR‐125b‐2‐3p‐WEE1 axis not only regulated CRC growth and metastasis but also contributed to chemotherapeutic resistance to CRC., Low expression of miR‐125b‐2‐3p in CRC was linked to lower chemotherapeutic sensitivity and poor survival. The lncRNA XIST promoted CRC invasion and migration by functioning as a ceRNA for miR‐125b‐2‐3p to mediate WEE1 expression. Our findings suggest that the lncRNA XIST‐miR‐125b‐2‐3p‐WEE1 axis not only regulated CRC growth and metastasis but also contributed to chemotherapeutic resistance to CRC, which may shed light on their targeted applications.

Background: Globo H (GH) is highly expressed in a variety of epithelial tumors with a limited expression in normal tissues rendering it a novel therapeutic target. OBI-999 is an antibody drug conjugate (ADC) consisting of a GH-specific monoclonal antibody conjugated with monomethyl auristatin E (MMAE) through a cathepsin B cleavable linker. MMAE is known to induce immunogenic cell death (ICD) which involves in the activation of cytotoxic T lymphocyte-driven adaptive immunity with long-term immunological memory. Aim: The aim of this study was to evaluate the synergistic effects of OBI-999 + pembrolizumab on tumor growth suppression in several xenograft tumor models. Methods: OBI-999-induced ICD was examined in vitro by the detection of damaging-associated molecular patterns (DAMPs) such as calreticulin (CRT), HMGB1, and ATP in incubated Globo H expressing cells. The synergistic effects with the combination of OBI-999 and pembrolizumab as well as the ICD-related immunity were assessed in vivo using advanced severe immunodeficient mice that were reconstituted with human peripheral blood mononuclear cells (PBMCs). Results: Incubation of OBI-999 with high GH expression cancer cell lines (HCC-1428, NCI-N87 and NCI-H526) and mid GH expression cancer cell line (SW-480) induced the release of DAMPs including CRT, HMGB1, and ATP, in a dose- and time-dependent manner, indicating that OBI-999 is capable of inducing ICD in vitro. In the high GH expression human breast cancer cell line HCC-1428 xenograft model, OBI-999+pembrolizumab exhibited significantly stronger inhibition of tumor growth compared to either OBI-999 or pembrolizumab alone. Similar synergistic effects were observed in other xenograft tumor models including gastric (NCI-N87), small cell lung (NCI-H526), and colorectal (SW-480) cancers. Analysis of tumor-infiltrating lymphocytes (TILs) in HCC-1428 humanized mice showed that OBI-999 + pembrolizumab induced populations of activated cytotoxic CD8 T-cells and mature dendritic cells. Pembrolizumab decreased PD-1 expression on CD8 and CD4 cells, and OBI-999 decreased PD-L1 expression on tumor cells, which reversed the exhausted status of immune cells and alleviated immunosuppression in the tumor microenvironment. Conclusion: We demonstrated significant synergistic effects of OBI-999 and pembrolizumab in several animal models. These synergistic effects may be attributed to the ability of OBI-999 to induce ICD, as demonstrated by the release of DAMPs in vitro and tumor-specific immunity in vivo, suggesting that OBI-999 can create a tumor microenvironment that enhances the function of pembrolizumab. The results suggest that combination therapy with OBI-999 and immune checkpoint inhibitors is warranted in human clinical studies. OBI-999 is currently in Phase 1/2 clinical trials for the treatment of advanced solid tumors with high GH expression (NCT04084366). Citation Format: Chun-Chung Wang, Chi-Huan Lu, Jhih-Jie Yang, Wan-Fen Li, Ming-Tain Lai. OBI-999, an anti-Globo H antibody drug conjugate, exhibits synergistic anti-tumor effect in combination with pembrolizumab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5946.

Background Propofol is a kind of common intravenous anaesthetic agent that plays an anti-tumor role in a variety of cancers, including ovarian cancer. However, the working mechanism of Propofol in ovarian cancer needs further exploration. Methods The viability and metastasis of ovarian cancer cells were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays. Flow cytometry was used to evaluate the cell cycle and apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the abundance of circular RNA vacuolar protein sorting 13 homolog C (circVPS13C) and microRNA-145 (miR-145). The target relationship between miR-145 and circVPS13C was predicted by circinteractome database and verified by dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNA-pull down assay. Western blot assay was used to detect the levels of phosphorylated extracellular regulated MAP kinase (p-ERK), ERK, p-MAP kinse-ERK kinase (p-MEK) and MEK, in ovarian cancer cells. Results Propofol treatment suppressed the viability, cell cycle and motility and elevated the apoptosis rate of ovarian cancer cells. Propofol up-regulated miR-145 in a dose-dependent manner. Propofol exerted an anti-tumor role partly through up-regulating miR-145. MiR-145 was a direct target of circVPS13C. Propofol suppressed the progression of ovarian cancer through up-regulating miR-145 via suppressing circVPS13C. Propofol functioned through circVPS13C/miR-145/MEK/ERK signaling in ovarian cancer cells. Conclusion Propofol suppressed the proliferation, cell cycle, migration and invasion and induced the apoptosis of ovarian cancer cells through circVPS13C/miR-145/MEK/ERK signaling in vitro.

In this work, nitrogen-doped graphene oxide quantum dots (N-GOQDs) were embedded into Mo2C to prepare a nanocomposite with great electrical conductivity and a large specific surface area. We manufactured an innovative electrochemical sensor based on N-GOQDs–Mo2C and a molecularly imprinted polymer (MIP) for the highly sensitive detection of indometacin (IDMC). The MIP was synthesized by electropolymerization using acrylamide as the functional monomer and IDMC as the template molecule. N-GOQDs–Mo2C was organized by an elementary hydrothermal approach and characterized by SEM, TEM, XRD and FT-IR. In the first-rank experimental conditions, the MIP electrochemical sensor shows a wide linear range from 10−15 M to 10−5 M for IDMC detection and the detection limit is as low as 9.508 × 10−16 M. Additionally, the manufactured sensor shows great selectivity for indometacin, excellent repeatability and stableness. The sensor can be applied to the detection of indometacin in tablets and water samples with fulfilling consequence.

Chronic renal failure (CRF) threatens human health greatly and attracts worldwide concerns of health professionals in the public health sector. In our preliminary study, we found that Compound capsule (Shengqing Jiangzhuo Capsule, SQJZJN) had a significant therapeutic effect on CRF. Quercetin is one of the main components of this Compound capsule. In this study, we investigated the effect of Quercetin monomer on CRF and the regulation of PI3k/Akt pathway. Network pharmacology analysis methods were employed to analyze the SQJZJN/Quercetin/PIK3R1 network relationships. In this study, a CRF rat model was prepared using the gavage adenine solution method and detected the indicators of Creatinine (Cr), Blood Urea Nitrogen (BUN), and Uric Acid (UA). After treating the rat model with Quercetin and PIK3R1-interfering lentivirus, respectively, we observed the changes on the histological morphology of the kidney and detected apoptosis using TUNEL staining. Gene and protein expression associated with renal function were detected using qPCR, WB and immunofluorescence. Quercetin was identified as the main ingredient of SQJZJN by the network pharmacological screening and Quercetin at 1.5 and 3 g/(kg.d) concentrations could effectively alleviate the CRF symptoms, reduce the levels of Cr, BUN, and UA, and markedly inhibit cell apoptosis demonstrated by the intragastric administration. Furthermore, the protein expression of p-PI3K, p-AKT, NLRP3, caspase1, AQP1, and AQP2 in all groups was detected by immunofluorescence and western blot assays, indicating that Quercetin could reduce the expression of NLRP3, caspase1, p-PI3k, and p-Akt, and increase the expression of AQP1 and AQP2 in the renal tissues of CRF rats. Being labeled with biotin and incubated with the total protein extracted from kidney tissues, Quercetin could bind to PIK3R1. Following the PIK3R1 interference lentivirus was injected into the CRF model rats by tail vein, the CRF symptoms were effectively alleviated in the PIK3R1 interference group, consistent with the effect of Quercetin. Taken together, Quercetin, a major component of SQJZJN, might minimize renal fibrosis and apoptosis in CRF rats by inhibiting the PI3k/Akt pathway through targeting PIK3R1. By regulating AQP1 and AQP2, both water retention and toxin accumulation were reduced.

The paper provided a simple method for preparing the β-carotene reference standard from a β-carotene food additive (96%) based on high speed countercurrent chromatography (HSCCC). The obtained material was qualitatively detected by IR, NMR, MS, the results showed the material was purified β-carotene, the purity of obtained β-carotene reference standard can be as high as 99%. The prepared reference standard can be used for quality control of related health food. The provided method is simple, universal, cheap, and the sample preparation can be enlarged to g grade.

Photocontrolled polymerization offers a convenient way to direct the reaction progress and tailor the polymer structures. Nevertheless, conjugated polymers are yet to be utilized as the photocatalyst in associated reactions. Herein, we employed poly(boron dipyrromethene

In this paper, the binding relationship between oligopeptides of edible fungi and monoamine oxidase A (MAO-A) was explored by computer simulation. The frequency of high affinity oligopeptides (F value) was calculated, and the MAO-A inhibitory peptide was screened. By simulating the hydrolysis of 27 proteins from 8 common edible fungi in China, the oligopeptides obtained by hydrolysis were docked with MAO-A to screen high affinity oligopeptides (docking fraction ≤ -120) and ultra-high affinity oligopeptides (docking fraction ≤ -160). At the same time, the F value was calculated to predict the inhibitory effect of edible fungi protein on MAO-A. A total of 430 high-affinity oligopeptides and 32 ultra-high-affinity oligopeptides were obtained by molecular docking after 27 proteins were simulated hydrolysis. Among them, the three oligopeptides with the highest docking were PQSTW (-195.952), PTSGW (-187.942) and QCQW (-180.007). In addition, the simulated hydrolyzed edible fungi all contained oligopeptides with strong inhibitory effect on MAO-A. In summary, this paper aims to screen MAO-A inhibitory peptides, provide new possibilities for high-speed screening of MAO-A inhibitory peptides, and provide a theoretical basis for exploring the potential value of edible fungi.

Ovarian damage induced by platinum-based chemotherapy seriously affects young women with cancer, manifesting as infertility, early menopause, and premature ovarian insufficiency. However, effective prevention strategies for such damage are lacking. Senescent cells may be induced by chemotherapeutic agents. We hypothesized that cisplatin can lead to senescence in ovarian cells during the therapeutic process, and senolytic drugs can protect animals against cisplatin-induced ovarian injury. Here, we demonstrated the existence of senescent cells in cisplatin-treated ovaries, identified the senescence-associated secretory phenotype, and observed significant improvement of ovarian function by treatment with metformin or dasatinib and quercetin (DQ) independently or in combination. These senotherapies improved both oocyte quality and fertility, increased the ovarian reserve, and enhanced hormone secretion in cisplatin-exposed mice. Additionally, attenuated fibrosis, reorganized subcellular structure, and mitigated DNA damage were observed in the ovaries of senotherapeutic mice. Moreover, RNA sequencing analysis revealed upregulation of the proliferation-related genes Ki, Prrx2, Sfrp4, and Megfl0; and the antioxidative gene H2-Q10 after metformin plus DQ treatment. Gene ontology analysis further revealed that combining senotherapies enhanced ovarian cell differentiation, development, and communication. In this study, we demonstrated that metformin plus DQ recovered ovarian function to a greater extent compared to metformin or DQ independently, with more follicular reserve, increased pups per litter, and reduced DNA damage. Collectively, our work indicates that senotherapies might prevent cisplatin-induced ovarian injury by removing senescent cells and reducing DNA damage, which represent a promising therapeutic avenue to prevent chemotherapy-induced ovarian damage.

Music style is tightly connected with listeners’ emotional processes and neural activities. However, it remains unclear how the brain works when different music styles are processed emotionally. The current study analyzed the neural activation associated with five music styles during emotion-evoking. Twenty non-musicians participated in the functional magnetic resonance imaging (fMRI) scanning and the emotional ratings of pleasure and arousal evoked by pop, rock, jazz, folk, and classical music. Results showed that classical music was associated with the highest pleasure rating and deactivation of the corpus callosum. Rock music was associated with the highest arousal rating and deactivation of the cingulate gyrus. Pop music activated the bilateral supplementary motor areas (SMA) and the superior temporal gyrus (STG) with moderate pleasure and arousal. As the first fMRI experiment investigating the relationship between the music style and emotion, it provides neural correlates of different music styles during emotion-evoking.

Lead-free K0.5Na0.5NbO3 (KNN)-based single crystals have been prepared by a seed-free, solid-state crystal growth method. The effects of the calcined temperature of ingredients on the growth, structure and electrical properties of the single crystals are systematically studied. Results show that increasing the calcined temperature is beneficial to the synthesis of pure orthorhombic-phase powder, but it hardly affects the phase structure of the single crystals. When the calcined temperature is in the range of 700–850 °C, it is more useful for obtaining larger KNN-based crystals. What is more, the width of the domains in the crystals first decreases and then increases with rising of the calcined temperature, which is in well agreement with the changing regularity of the structure and electrical properties. The single crystals with good electrical properties can be obtained in a wide calcined-temperature range of 700–850 °C: the piezoelectric constant d33 of 155–209 pC N−1, dielectric constant e of 291–389, dielectric loss tanδ of 2.0–3.4%, and remnant polarization Pr of 25.4–49.1 μC cm−2.

Saccharomyces cerevisiae acts as a bio-foundry for producing natural products. S. cerevisiae ’s intrinsic pathways highlight microbial cell factories to produce pharmaceutics, food additive, and fine chemicals. For high-titer, yield, and conversion of target compounds, the critical point is that fine-tuning and optimizing intracellular metabolic flux in the yeast cell. Acetyl-CoA is the fundamental precursor for central metabolism and heterologous pathway. In comparison, acetyl-CoA compartmentalizes in mitochondria, nucleus, peroxisome subcellular, and cytosol. Most of the pathway enzymes are expressed in S. cerevisiae cytosol. So, we summarized the fine-tuning strategies of acetyl-CoA synthesis in cytosol matrix. The new acetyl-CoA pathway (phosphoketolase, phosphotransacetylase, and acetaldehyde dehydrogenase, PK/PTA-ADA) shows a high conversion ratio from the carbon source. The PK/PTA-ADA pathway presents improved redox balance, limited ATP requirement, and reduced carbon loss to CO2. Moreover, the heterologous ATP-dependent citrate lyase precisely converts mitochondria metabolism into acetyl-CoA. Knock-out acetyl-CoA depletion pathways retain high acetyl-CoA titer in the cytosol. The continuous metabolic engineering on PK/PTA-ADA pathway is expected for higher acetyl-CoA titer. The Mevalonate pathway has been engineered to produce terpenoids in S. cerevisiae . The exogenous HMG-CoA synthase and HMG-CoA reductase boost mevalonate pathway from acetyl-CoA. Further, the diversified terpenoids are generated from C5 unite Isopentenyl diphosphate and its’ isomer dimethylallyl diphosphate. Intrinsic farnesyl diphosphate synthase (Erg20) shows both dimethylallyltransferase (geranyl diphosphate, C10 product) and geranyltransferase (farnesyl diphosphate, C15 product) activity. The F96W/N127W mutations in Erg20 caused steric hindrance for geranyl diphosphate substrate. So, geranyl diphosphate is accumulated to produce C10 terpenoids or meroterpenoids. Moreover, geranylgeranyl diphosphate synthase (CrtE) convert farnesyl diphosphate (C15) into geranylgeranyl diphosphate (C20) for carotene, lycopene, astaxanthin, and taxol, etc. Interestingly, the novel isopentenol utilization pathway has been constructed in E. coli and Y. lipolytica to supply IPP and IMAPP precursors from isopentanol. This alternative pathway could relieve the acetyl-CoA supply burden in the mevalonate pathway. Fatty acid synthase (FAS) produces fatty acid with specific carbon length and derivatives from acetyl-CoA and malonyl-CoA. Acetyl-CoA carboxylase (ACC1) catalyzes acetyl-CoA to produce malonyl-CoA, which is utilized as the carbon unite in fatty acid pathway. Overexpression of ACC1 and mitochondria located isoenzyme Hfa1 significantly improves fatty acid production. FAS in S. cerevisiae is an α6β6 heterodimer protein and these catalytic domains are engineered to produce specific fatty acids. Directed mutations in ketoacyl synthase (KS), acetyltransferase (AT), and malonyl/palmitoyl transferase (MPT) domains engage FAS to generate high-yield short/medium fatty acid (C6 and C8). Furthermore, fatty acid reductase and acyl-ACP reductase convert fatty acid or fatty acyl-ACP to fatty aldehydes, respectively. Aldehyde deformylating oxygenase produces alkanes from fatty aldehydes substrate. Significantly, fatty acid-derived bio hydrocarbons showed closets properties to petroleum fuel. We reviewed the metabolic strategies of acetyl-CoA synthesis, the novel mevalonate pathway and fatty acid synthesis. These strategies may be valuable for producing high-yield terpene and fatty acid derivatives in Saccharomyces cerevisiae .

Pathogenesis and treatment for diabetic neuropathy are still complex. A deficit of neurotrophic factors affecting Schwann cells is a very important cause of diabetic neuropathy. Neuritin is a newly discovered potential neurotrophic factor. In this study, we explored the effect of exogenous neuritin on survivability and functions of diabetic Schwann cells of rats with experimental diabetic neuropathy. Diabetic neuropathy was induced in rats. 12‐week diabetic rats contrasted with non‐diabetic normal rats had decreased levels of serum neuritin and slowed nerve conduction velocities (NCVs). Schwann cells isolated from these diabetic rats and cultured in high glucose showed reduced cell neuritin mRNA and protein and supernatant neuritin protein, increased apoptosis rates, increased caspase‐3 activities and progressively reduced viability. In contrast, exogenous neuritin treatment reduced apoptosis and improved viability, with elevated Bcl‐2 levels (not Bax) and decreased caspase‐3 activities. Co‐cultured with diabetic Schwann cells pre‐treated with exogenous neuritin in high glucose media, and diabetic DRG neurons showed lessened decreased neurite outgrowth and supernatant NGF concentration occurring in co‐culture of diabetic cells. Exogenous neuritin treatment ameliorated survivability and functions of diabetic Schwann cells of rats with diabetic neuropathy. Our study may provide a new mechanism and potential treatment for diabetic neuropathy.

Background The photosystem II (PSII)-inhibiting herbicides are important for Australian farmers to control Lolium rigidum Gaud. and other weed species in trazine tolerant (TT)-canola fields. A L. rigidum population (R) collected from a TT-canola field from Western Australia showed multiple resistance to PSII, acetyl-coenzyme A carboxylase (ACCase) and acetolactate synthase (ALS) inhibitors. The mechanisms of multiple resistance in this R population were determined. Results The R population showed a low-level (about 3.0-fold) resistance to the PSII-inhibiting herbicides metribuzin and atrazine. Sequencing of the psbA gene revealed no differences between the R and susceptible (S) sequences. Furthermore, [14 C]-metribuzin experiments found no significant difference in metribuzin foliar uptake and translocation between the R and S plants. However, [14 C]-metribuzin metabolism in R plants was 2.3-fold greater than in S plants. The cytochrome P450 monooxygenase inhibitor piperonyl butoxide (PBO) enhanced plant mortality response to metribuzin and atrazine in both R and S populations. In addition, multiple resistance to ALS and ACCase inhibitors are due to known resistance mutations in ALS and ACCase genes. Conclusion The results demonstrate that enhanced metribuzin metabolism likely involving cytochrome P450 monooxygenase contributes to metribuzin resistance in Lolium rigidum. This is the first report of metabolic resistance to the PSII-inhibiting herbicide metribuzin in Australian Lolium rigidum. © 2020 Society of Chemical Industry.

Summary The novel coronavirus disease 2019 (COVID-19) occurred in China (mainly in Wuhan, Hubei Province) at the end of December 2019. Henan province is located in the center of China, borders on Hubei province by land in the south with the nearest distance of 200 kilometers to Wuhan. As the inland provinces in mainland China, frequent communication in transportation and population flow make it difficult to confine the pandemic, which is similar to that in the landlocked countries in Europe. The expected cases in Henan were mainly imported. A bundle of intervention strategies were adopted from 26 January 2020 to cut off the spread between the infected patients and the native residents. The pandemic was controlled 2 month later after the bundle of strategies was adopted although the number of cases continued to increase explosively during the first 10 days. A total of 1273 cases were confirmed, 1251 patients were cured, 22 patients died, and 1 patient was still in hospital until 29 March 2020. The peak of daily increased cases was 109 cases. Our data show that COVID-19 is highly infectious and easy to cause an outbreak, but it can be controlled by early effective interventions. A bundle of strategies according to the specific situation of each country is suggested to be implemented as early as possible.