Remarkable Off-On Tunable Solid-State Luminescence by the Regulation of Pyrene Dimer.

It is always a challenge to achieve "off-on" luminescent switch by regulating non-covalent interactions. Herein, we report a unique strategy for constructing high performance "off-on" tunable luminescent materials utilizing a novel molecule (TFPA) consist of pyrene and cyanostilbene. The pristine crystal of TFPA is almost non-emissive. Upon grinding/UV irradiation, an obvious luminescence enhancement is observed. Theoretical and experimental results revealed the underlying mechanism of this intriguing "off-on" switching behavior. The non-emissive crystal consists of ordered H-aggregates, with adjacent two molecules stacked in an anti-parallel manner and no overlapped area in pyrene moieties. When external force is applied by grinding or internal force is introduced through the photoisomerization, the dimer structures are facilitated with shorter intermolecular distances and better overlapping of pyrene moieties. In addition, the "on" state can recover to "off" state under thermal annealing, showing good reversibility and applicability in intelligence material. The present results promote an in-depth insight between packing structure and photophysical property, and offer an effective strategy for the construction of luminescence "off-on" switching materials, toward the development of stimuli-responsive luminescent materials for anti-counterfeiting.

Structure determination using high-order spatial correlations in single-particle X-ray scattering.

Single-particle imaging using X-ray free-electron lasers (XFELs) is a promising technique for observing nanoscale biological samples under near-physiological conditions. However, as the sample's orientation in each diffraction pattern is unknown, advanced algorithms are required to reconstruct the 3D diffraction intensity volume and subsequently the sample's density model. While most approaches perform 3D reconstruction via determining the orientation of each diffraction pattern, a correlation-based approach utilizes the averaged spatial correlations of diffraction intensities over all patterns, making it well suited for processing experimental data with a poor signal-to-noise ratio of individual patterns. Here, a method is proposed to determine the 3D structure of a sample by analyzing the double, triple and quadruple spatial correlations in diffraction patterns. This ab initio method can reconstruct the basic shape of an irregular unsymmetric 3D sample without requiring any prior knowledge of the sample. The impact of background and noise on correlations is investigated and corrected to ensure the success of reconstruction under simulated experimental conditions. Additionally, the feasibility of using the correlation-based approach to process incomplete partial diffraction patterns is demonstrated. The proposed method is a variable addition to existing algorithms for 3D reconstruction and will further promote the development and adoption of XFEL single-particle imaging techniques.

Coupled Effect of Low Temperature and Electrolyte Immersion on the Tensile Properties of Separators in Lithium-Ion Batteries.

The performance degradation at low temperatures and frequent safety accidents have aggravated security risks and inhibited the long-term service of lithium-ion batteries (LIBs). As a key component of LIBs, the separator has a great impact on the performance and safety of the battery. In this study, tensile tests of two commercial polyolefin separators (Celgard 2325 and Celgard PE) are performed under low-temperature and immersion conditions. Four representative temperature points and dimethyl carbonate [(DMC), the common solvent in electrolytes] are selected to investigate the coupling effect on the mechanical properties of the separators. The results show that both the separators have anisotropy, but the performance of Celgard 2325 varies more significantly than that of Celgard PE along different directions. Additionally, it is found that with a decrease in the temperature, the tensile strength of the two separators increases, while the elongation decreases. Electrolyte immersion induces a softening tendency in Celgard 2325. Due to the special effect of the residual electrolyte on polyethylene fibers, Celgard PE shows the opposite result. Furthermore, the effect of low temperature is revealed by the analysis of the crystallinity and molecular structure, which can be obtained by X-ray diffraction and Raman spectroscopy, respectively. In addition, the contact angle is measured to describe the wettability variation related to low temperature. The present work provides a theoretical basis and experimental data for the application and development of separators.

STL127705 synergize with olaparib in castration-resistant prostate cancer by inhibiting homologous recombination and non-homologous end-joining repair.

Therapeutic resistance to androgen-deprivation therapy is a major challenge for prostate cancer therapy. The present study aims to explore the effects of poly (ADP-ribose) polymerase (PARP) inhibitor olaparib and STL127705 on castration-resistant prostate cancer. Cell lines including PC-3 and enzalutamide-resistant LNCaP (erLNCaP) cells were treated with enzalutamide, enzalutamide plus olaparib, enzalutamide plus STL127705, or the combination of olaparib, STL127705, and enzalutamide. Cell viabilities and cell apoptosis were determined using the sulforhodamine B (SRB) assay and Annexin V/propidium iodide staining, respectively. Flow cytometry assay was applied to determine γH2AX intensity and the percentage of homologous recombination and non-homologous end-joining. Besides, a tumor-bearing animal model was established and treated with drugs as for cell lines. STL127705 and olaparib enhanced cytotoxicity of enzalutamide on erLNCaP and PC-3 cells. Furthermore, STL127705 and olaparib promoted enzalutamide-induced cell apoptosis and enhanced γH2AX intensity. In vitro study also showed that the combination of STL127705, olaparib, and enzalutamide inhibited homologous recombination and non-homologous end-joining repair systems in PC-3 cells. In vivo study demonstrated that the combination of STL127705, olaparib, and enzalutamide exhibited a significant anti-tumor effect. STL127705 combined with olaparib have a potential therapeutic effect on castration-resistant prostate cancer through inhibiting homologous recombination and non-homologous end-joining repair.

Machine learning-assisted crystal engineering of a zeolite.

It is shown that Machine Learning (ML) algorithms can usefully capture the effect of crystallization composition and conditions (inputs) on key microstructural characteristics (outputs) of faujasite type zeolites (structure types FAU, EMT, and their intergrowths), which are widely used zeolite catalysts and adsorbents. The utility of ML (in particular, Geometric Harmonics) toward learning input-output relationships of interest is demonstrated, and a comparison with Neural Networks and Gaussian Process Regression, as alternative approaches, is provided. Through ML, synthesis conditions were identified to enhance the Si/Al ratio of high purity FAU zeolite to the hitherto highest level (i.e., Si/Al = 3.5) achieved via direct (not seeded), and organic structure-directing-agent-free synthesis from sodium aluminosilicate sols. The analysis of the ML algorithms' results offers the insight that reduced Na2O content is key to formulating FAU materials with high Si/Al ratio. An acid catalyst prepared by partial ion exchange of the high-Si/Al-ratio FAU (Si/Al = 3.5) exhibits improved proton reactivity (as well as specific activity, per unit mass of catalyst) in propane cracking and dehydrogenation compared to the catalyst prepared from the previously reported highest Si/Al ratio (Si/Al = 2.8).

Alfuzosin ameliorates diabetes by boosting PGK1 activity in diabetic mice.

AIMS: Diabetes mellitus (DM) has become a global problem, causing a huge economic burden. The purpose of this study is to find a new potential method and mechanism for the treatment of DM. MAIN METHODS: The oxidation, glycation and insulin resistance cell models were built to screen the potential anti-diabetic chemicals. Then the DM mice were induced by the combination of high-fat diet (HFD) and intraperitoneal injection of streptozotocin (50 mg/kg) for five days. The alfuzosin (1.2 mg/kg) was administered by intraperitoneal injection once daily for sequential 12 weeks. Fasting blood glucose, blood lipid, oxidative stress and key markers of glucose metabolism were detected. PGK1/AKT/GLUT4 pathway related proteins were analyzed by Western blot. KEY FINDINGS: Alfuzosin ameliorated oxidative stress, glycative stress and insulin resistance in HepG2 cells. Further, in a high-fat diet/streptozotocin (HFD/STZ)-induced diabetic mouse model, alfuzosin reduced fasting blood glucose, improved insulin sensitivity. Mechanically, alfuzosin activated PGK1 directly to stimulate the protein kinase B (AKT) signaling pathway, thus facilitating glucose uptake as well as improving insulin resistance. SIGNIFICANCE: The present finding has shed a new light on the treatment of DM and provides validation for PGK1 as a therapeutic target for DM.

Sulfathiazole treats type 2 diabetes by restoring metabolism through activating CYP19A1.

Globally, diabetes mellitus has been a major epidemic bringing metabolic and endocrine disorders. Currently, 1 in 11 adults suffers from diabetes mellitus, among the patients >90% contract type 2 diabetes mellitus (T2DM). Therefore, it is urgent to develop new drugs that effectively prevent and treat type 2 diabetes through new targets. With high-throughput screening, we found that sulfathiazole decreased the blood glucose and improved glucose metabolism in T2DM mice. Notably, we discovered that sulfathiazole treated T2DM by activating CYP19A1 protein to synthesize estrogen. Collectively, sulfathiazole along with CYP19A1 target bring new promise for the better therapy of T2DM.

A robust soft sensor based on artificial neural network for monitoring microbial lipid fermentation processes using Yarrowia lipolytica.

Microbial oils produced by Yarrowia lipolytica offer an environmentally friendly and sustainable alternative to petroleum as well as traditional lipids from animals and plants. The accurate measurement of fermentation parameters, including the substrate concentration, dry cell weight, and lipid accumulation, is the foundation of process control, which is indispensable for industrial lipid production. However, it remains a great challenge to measure the complex parameters online during the lipid fermentation process, which is nonlinear, multivariate, and characterized by strong coupling. As a type of AI technology, the artificial neural network model is a powerful tool for handling extremely complex problems, and it can be employed to develop a soft sensor to monitor the microbial lipid fermentation process of Y. lipolytica. In this study, we first analyzed and emphasized the volume of sodium hydroxide and dissolved oxygen concentration as central parameters of the fermentation process. Then, a soft sensor based on a four-input artificial neural network model was developed, in which the input variables were fermentation time, dissolved oxygen concentration, initial glucose concentration, and additional volume of sodium hydroxide. This provides the possibility of online monitoring of dry cell weight, glucose concentration, and lipid production with high accuracy, which can be extended to similar fermentation processes characterized by the addition of bases or acids, as well as changes of the dissolved oxygen concentration.

Quinacrine attenuates diet-induced obesity by inhibiting adipogenesis via activation of AMPK signaling.

Obesity, a global epidemic chronic metabolic disease, urgently demands novel therapies. As an antimalarial drug, quinacrine has not been reported for its anti-obesity effect to our knowledge. This study aimed to explore the ability of quinacrine to attenuate obesity. In an in vitro adipogenic model, quinacrine exhibited an outstanding suppression on adipogenesis of 3T3-L1 cells, mainly by activating the AMPK (Adenosine 5'-monophosphate (AMP)-activated protein kinase) signaling pathway to regulate preadipocytes differentiation and lipid accumulation. In addition, C57BL/6N female mice were fed with high-fat diet and high-fructose water for 14 weeks to establish an obesity model, followed by oral administration of quinacrine or orlistat. After 9 weeks of treatment, quinacrine significantly reduced the body weight and energy intake, ameliorated the impaired glucose tolerance and restored the homeostasis of serum lipids. Also, quinacrine improved lipid profile and optimized the expression of AMPK signaling pathway related proteins in livers and adipose tissues of obese mice. Quinacrine reverses obesity through activating AMPK phosphorylation to down-regulate adipogenesis, along with lowering the risk of type 2 diabetes and atherosclerosis. It should be a novel application for the treatment of obesity and its associated diseases.

[Clinical observational study on the treatment of oligozoospermia with Shizi Sanhua decoction combined with Nuoyu].

OBJECTIVE: To study the clinical therapeutic effect as well as drug effectiveness and safety of Shizi Sanhua decoction combined with Nuoyu in the treatment of oligozoospermia in men. METHODS: 102 patients with oligozoospermia diagnosed at Longhua Hospital of Shanghai University of Traditional Chinese Medicine from February 2022 to March 2023 were selected and randomly divided into 3 groups. The treatment group was treated with Shizi Sanhua Decoction + Nuoyu; the traditional Chinese medicine group was treated with Shizi Sanhua Decoction; and the Nuoyu nutrient group was treated with Nuoyu nutrient. A review assessment and record were made after one course of treatment (3 months). RESULTS: A total of 102 patients completed the trial due to the treatment process. There were 34 cases in each of the traditional Chinese medicine group, the Nuoyu nutrient group, and the treatment group. Clinical efficacy: total effective rate of 52.94% in the traditional Chinese medicine group; 58.82% in the Nuoyu nutrient group; 82.35% in the treatment group. The clinical efficacy of the treatment group was better than that of the traditional Chinese medicine group and the Nuoyu nutrient group (P<0.05), which was statistically significant. Semen routine: the treatment group was better than the traditional Chinese medicine group and Nuoyu nutrient group in improving the total number of sperm and sperm concentration. CONCLUSION: The semen concentration and forward sperm count of patients with oligozoospermia treated with Shizi Sanhua Decoction combined with Nuoyu improved more significantly, and the clinical efficacy was remarkable. And the clinical efficacy is not affected by age and disease duration. It can be popularized and applied as a treatment for oligozoospermia.

Primaquine activates Keratin 7 to treat diabetes and its complications.

Background: The global prevalence of type 2 diabetes mellitus (T2DM) raises the rates of its complications, such as diabetic nephropathy and cardiovascular diseases. To conquer the complications, new strategies to reverse the deterioration of T2DM are urgently needed. In this project, we aimed to examine the hypoglycemic effect of primaquine and explore its specific target. Methods: In vitro T2DM insulin resistance model was built in HepG2 cells to screen the potential anti-diabetic chemicals. On the other hand, the potential protein targets were explored by molecular docking. Accordingly, we chose C57BL/6 N mice to establish T2DM model to verify the effect of the chemicals on anti-hyperglycemia and diabetic complications. Results: By targeting the Keratin 7 (K7) to activate EGFR/Akt glucose metabolism signaling pathway, primaquine poses a potent hypoglycemic effect. The level of acetyl-CoA is enhanced markedly, supporting that primaquine upregulates the aerobic glycolysis. Moreover, primaquine ameliorates kidney function by reducing the secretion of urinary proteins and creatinine, especially for the urea nitrogen which is significantly decreased compared to no-treatment T2DM mice. Notably, primaquine restores the level of plasma low-density lipoprotein cholesterol (LDL-C) nearly to normal, minimizing the incidence of cardiovascular diseases. Conclusions: We find that primaquine may reverse the dysregulated metabolism to prevent diabetic complications by stimulating EGFR/Akt signaling axis, shedding new light on the therapy of T2DM. Graphical abstract: Insulin resistance is characterized by reduced p-Akt and glucose metabolism, dominated by anaerobic glycolysis. Primaquine activates the complex made of K7 and EGFR, further stimulating Akt phosphorylation. Then, p-Akt promotes the aerobic glucose metabolism and upregulates Ac-CoA to mobilize TCA cycle, improving insulin sensitivity. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01135-8.

Temperature-Shift-Induced Mechanical Property Evolution of Lithium-Ion Battery Separator Using Cyclic Nanoindentation.

The evolution of mechanical properties of separators affected by temperature shifts is imperative for the performance of the lithium-ion battery. The flexible film characteristics hinder the evaluation of the micromechanical properties of separators. In the present study, considering the susceptibility of separators to temperature fluctuations, the temperature distribution of the battery during the discharging process at subzero temperature is obtained. Three sets of separator samples subjected to various temperature shifts are prepared. Through multicycle depth-sensitive nanoindentation, the temperature-dependent weakening of elastic modulus and hardness of separators is experimentally verified. Moreover, the variation trends of elastic modulus, hardness, and hysteresis response of the separator specimens in terms of temperature are investigated via extracting from the multicycle loading-unloading nanoindentation responses. The temperature-dependent variations in the elastic modulus of the separator were investigated by following heating, cooling, and thermostatic processes. Meanwhile, the indentation tests also verify that the effect of temperature shifts on the hardness exhibits an attenuation trend when heating or cooling is followed by a thermostatic process. The variation analysis of nanoindentation hardness as a function of temperature shifts shows typical size effects dependent on the nanoindentation depth. The temperature-induced residual stress and elemental distribution are also analyzed through characterization using X-ray diffraction and energy-dispersive X-ray spectroscopy, respectively. The obtained evolution law of temperature shift-induced mechanical properties of a separator could facilitate the optimal design of the separators and provide the supporting data to enhance the safety performance of lithium-ion batteries.

Lamivudine remedies alcoholism by activating acetaldehyde dehydrogenase.

Acute ethanol intoxication has become an alarming health problem. In the present study, we discover the beneficial effect of lamivudine on alcoholism in mice. Our results indicate that lamivudine decreases serum alcohol concentration dramatically, and potently activates acetaldehyde dehydrogenase (ALDH) to accelerate the conversion of acetaldehyde to acetic acid, which is finally metabolized by tricarboxylic acid cycle to be CO2 and H2O. Also, lamivudine significantly improves symptoms post drinking, such as prolonging alcohol tolerance time and shortening sobering time, as well as reducing the death rate. This work will provide new strategies for the prevention and treatment of acute alcoholism.

Determining the origin of poor electronic conductivity and ultrafast ionic conductivity in Na3V2(PO4)2FO2 based on first principles and ab initio molecular dynamics methods.

Sodium ion technology is increasingly investigated as a low-cost solution for grid storage applications. Among the reported cathode materials for sodium-ion batteries, Na3V2(PO4)2FO2 is considered as one of the most promising materials due to its high operation voltage and good cyclability. Here, the de-sodiumization process of Na3V2(PO4)2FO2 has been systematically examined using first-principles calculations to uncover the fundamental questions at the atomic level. Four stable intermediate products during the de-sodiumization process are firstly determined based on the convex hull, and three voltage platforms are then predicted. Except for two voltage platforms (3.37 V and 3.75 V) close to the experimental values, the platform up to 5.28 V exceeds the stability window (4.8 V) of a typical electrolyte, which was not observed experimentally. Excitingly, the change of volume is only 2% during the sodiumization process, which should be the reason for the good cycling stability of this material. Electronic structure analysis also reveals that the valence states of V ions will be changed from V5+ to V4+ during the sodiumization process, resulting in a weak Jahn-Teller distortion in VO5F octahedra, and then making the lattice-constants asymmetrically change. More seriously, combined with a bandgap of 2.0 eV, the conduction band minimum mainly composed of V-t2g non-bonding orbitals has strong localized characteristics, which should be the intrinsic origin of poor electron transport properties for NaxV2(PO4)2FO2. Nonetheless, benefiting from the layer-like structure features with F-segmentation, this material has an ultrafast sodium ionic conductivity comparable to that of NASICON, with an activation energy of only 82 meV. Therefore, our results indicate that maintaining layer-like features and regulating V atoms will be important directions to improve the performance of NaxV2(PO4)2FO2.

Acyclovir alleviates insulin resistance via activating PKM1 in diabetic mice.

AIMS: Diabetes mellitus (DM) is a major global health threat characterized by insulin resistance. A new tactic to ameliorate insulin resistance, thereby reversing the exacerbation of DM, is urgently needed. The work is aiming to provide a new strategy for DM treatment as well as to identify new targets. MAIN METHODS: C57BL/6 N mice were raised with high-fat diet (HFD) and infused with streptozotocin (STZ) to induce diabetes. The blood glucose, serum insulin, blood lipid and oxidative stress were detected. In vitro insulin resistance model experiment has been made to examine the molecular mechanisms underlying anti-diabetic effect of potential active chemicals in human hepatocellular carcinoma cells (HepG2). KEY FINDINGS: Acyclovir, an antiviral nucleotide analog, alleviates insulin resistance by reducing blood lipids as well as oxidative stress and elevating insulin sensitivity on diabetic mice, which is in accord with results in the insulin resistance model of HepG2 cells. Mechanically, acyclovir stimulates pyruvate kinase M1 (PKM1) directly to activate adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/Sirtuin1 (SIRT1) signaling pathway, thus improving insulin resistance. SIGNIFICANCE: The present study supports that acyclovir should be translated to remedy DM, and PKM1 might be a valuable target to develop new medicines.

Achieving high speed of the stick-slip piezoelectric actuator at low frequency by using a two-stage amplification mechanism (TSAM).

The stick-slip piezoelectric actuator is a promising type for precision positioning with large stroke and high resolution; however, it is still challenging to achieve high motion speed at a relatively low driving frequency. To solve this problem, a novel two-stage amplification mechanism (TSAM) was designed, and correspondingly, a stick-slip piezoelectric actuator was developed. The structure, two-stage amplification principle, and motion processes of the designed actuator were addressed in detail, followed by analyzing the displacement amplification ratio and stress of TSAM via the elastic beam method and finite element method, respectively. Then, the actuator prototype was fabricated, and its output performances were tested under various experimental parameters. By comparative analysis with the actuator that only used the first-stage amplification hinge, the significant improvement in stepping displacement was verified when employing the TSAM. The resultant maximum motion speed was 20.05 mm/s, achieved under the locking force of 2 N, the input voltage of 100 V, and the driving frequency of 700 Hz. In addition, the developed actuator still maintained competitive motion resolution and loading capacity. The comparative analysis with some previous studies further indicated that the developed actuator with the TSAM had successfully achieved a relatively high motion speed at a relatively low driving frequency, which would be beneficial to the practical application.

miR-143 mediates abiraterone acetate resistance by regulating the JNK/Bcl-2 signaling pathway in prostate cancer.

Background: miR-143 is known to be downregulated in various cancer cells and tumors and generally plays a tumor-suppressor role. miR-143. However, the role of miR-143 in the mediation of the sensitivity of prostate cancer cells to abiraterone acetate remains unrevealed. Methods: The expression levels of miRNAs were determined by miRNA microarray and quantitative real-time PCR (qRT-PCR). The protein levels were assessed by Western blot assay. Cell viability and apoptosis were respectively measured by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Results: We identified that miR-143 was significantly downregulated in PC3-AbiR cells compared to PC3 cells. Overexpression of miR-143 promoted PC-AbiR sensitivity to abiraterone acetate in vitro and in vivo. We also revealed that miR-143 upregulation inhibited p-JNK (c-Jun N-terminal kinases) and increased p-Bcl2 (B-cell lymphoma 2), contributing to abiraterone acetate-induced apoptosis in PC3-AbiR cells. Finally, we showed that the combination of miR-143 and abiraterone acetate exerted the most profound tumor inhibition effect and prolonged the mice survival rate in PC3-AbiR tumor-bearing mice. Conclusion: Upregulation of miR-143 may serve as a new strategy to enhance the therapeutical effect of abiraterone acetate on prostate cancer patients who are resistant to abiraterone acetate.

The fate of methylmercury through the formation of bismethylmercury sulfide as an intermediate in mice.

A previous study by our group indicated that methylmercury (MeHg) is biotransformed to bismethylmercury sulfide [(MeHg)2S)] by interaction with reactive sulfur species (RSS) produced in the body. In the present study, we explored the transformation of MeHg to (MeHg)2S in the gut and the subsequent fate of (MeHg)2S in vitro and in vivo. An ex vivo experiment suggested the possibility of the extracellular transformation of MeHg to (MeHg)2S in the distal colon, and accordingly, the MeHg sulfur adduct was detected in the intestinal contents and feces of mice administered MeHg, suggesting that (MeHg)2S is formed through reactions between MeHg and RSS in the gut. In a cell-free system, we found that (MeHg)2S undergoes degradation in a time-dependent manner, resulting in the formation of mercury sulfide and dimethylmercury (DMeHg), as determined by X-ray diffraction and gas chromatography/mass spectrometry, respectively. We also identified DMeHg in the expiration after the intraperitoneal administration of (MeHg)2S to mice. Thus, our present study identified a new fate of MeHg through (MeHg)2S as an intermediate, which leads to conversion of volatile DMeHg in the body.