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Metabolic syndrome is a complex group of metabolic disorders with an increasing global incidence rate, posing a serious threat to human health. Sodium-glucose linked transporter 2 (SGLT2) inhibitors are a new type of oral hypoglycemic drug. SGLT2 inhibitors not only lower blood glucose level in a non-insulin-dependent manner by inhibiting glucose reabsorption by renal proximal convoluted tubular epithelial cell to promote urinary glucose excretion, but also by improving islet ß cell function, reducing inflammatory responses, and inhibiting oxidative stress. In addition, SGLT2 inhibitors can reduce body weight through osmotic diuresis and increase fat metabolism; reduce blood pressure by inhibiting excessive activation of sympathetic nervous system and by improving vascular function. They can also improve blood lipids by increasing degradation of triacylglycerol; reduce blood uric acid by promoting uric acid excretion in kidney and intestine, and by reducing uric acid synthesis. This article reviews the effects and mechanisms of SGLT2 inhibitors on multiple metabolic disorders in metabolic syndrome and explores their potential application in metabolic syndrome treatment.

Tumor microenvironment responsive Mn3O4 nanoplatform for in vivo real-time monitoring of drug resistance and photothermal/chemodynamic synergistic therapy of gastric cancer.

BACKGROUND: Postoperative chemotherapy for gastric cancer often causes multidrug resistance (MDR), which has serious consequences for therapeutic effects. Individualized treatment based on accurate monitoring of MDR will greatly improve patient survival. RESULTS: In this article, a self-enhanced Mn3O4 nanoplatform (MPG NPs) was established, which can react with glutathione to produce Mn2+ to enhance T1-weighted magnetic resonance imaging (MRI) and mediate in vivo real-time MDR monitoring. In vitro MRI results showed that MRI signals could be enhanced in the presence of hydrogen peroxide and glutathione and at acidic pH. In vivo MRI results indicated that MPG NPs could specifically target MDR cells, thereby realizing real-time monitoring of MDR in gastric cancer. Furthermore, MPG NPs have good chemodynamic activity, which can convert the endogenous hydrogen peroxide of tumor cells into highly toxic hydroxyl radical through Fenton-like reaction at acidic pH to play the role of chemodynamic therapy. In addition, Mn3O4 can significantly enhance the chemodynamic therapy effect because of its good photothermal conversion effect. Furthermore, in situ photothermal/chemodynamic synergistic therapy obtained remarkable results, the tumors of the mice in the synergistic therapy group gradually became smaller or even disappeared. CONCLUSIONS: MPG NPs have good biocompatibility, providing a good nanoplatform for real-time monitoring and precise diagnosis and treatment of MDR in gastric cancer.

Captopril related kidney damage: renal afferent arteriolar responses to angiotensin II and inflammatory signaling.

Captopril can have nephrotoxic effects, which are largely attributed to accumulated renin and "escaped" angiotensin II (Ang II). Here we test whether angiotensin converting enzyme-1 (ACE1) inhibition damages kidneys via alteration of renal afferent arteriolar responses to Ang II and inflammatory signaling. C57Bl/6 mice were given vehicle or captopril (60 mg/kg per day) for four weeks. Hypertension was obtained by minipump supplying Ang II (400 ng/kg per min) during the second 2 weeks. We assessed kidney histology by periodic acid-Schiff (PAS) and Masson staining, glomerular filtration rate (GFR) by FITC-labeled inulin clearance, and responses to Ang II assessed in afferent arterioles in vitro. Moreover, arteriolar H2O2 and catalase, plasma renin were assayed by commercial kits, and mRNAs of renin receptor, transforming growth factor-ß (TGF-ß) and cyclooxygenase-2 (COX-2) in the renal cortex, mRNAs of angiotensin receptor-1 (AT1R) and AT2R in the preglomerular arterioles were detected by RT-qPCR. The results showed that, compared to vehicle, mice given captopril showed lowered blood pressure, reduced GFR, increased plasma renin, renal interstitial fibrosis and tubular epithelial vacuolar degeneration, increased expression of mRNAs of renal TGF-ß and COX-2, decreased production of H2O2 and increased catalase activity in preglomerular arterioles and enhanced afferent arteriolar Ang II contractions. The latter were blunted by incubation with H2O2. The mRNAs of renal microvascular AT1R and AT2R remained unaffected by captopril. Ang II-infused mice showed increased blood pressure and reduced afferent arteriolar Ang II responses. Administration of captopril to the Ang II-infused mice normalized blood pressure, but not arteriolar Ang II responses. We conclude that inhibition of ACE1 enhances renal microvascular reactivity to Ang II and may enhance important inflammatory pathways.

Gold nanoparticle-decorated metal organic frameworks on immunochromatographic assay for human chorionic gonadotropin detection.

Gold nanoparticle-decorated metal organic frameworks (MOF@AuNPs) with significantly enhanced color signal intensity were synthesized through in situ growth of AuNPs on the MOF skeleton. The resultant MOF@AuNP nanocomposites were characterized with 16.7-fold higher absorbance than conventional 40 nm AuNPs (AuNP40). Thus, for the first time, we applied it as a signal amplification label to improve the immunochromatographic assay (ICA) of human chorionic gonadotropin (HCG). The detection limit of our enhanced ICA was 1.69 mIU/mL, which is ca. 10.6-fold improvement in sensitivity compared to traditional AuNP40-ICA. The recoveries of this MOF@AuNPs-ICA ranged from 86.03 to 119.22%, with coefficients of variation of 3.05 to 13.74%. The reliability and practicability were further validated by the clinically used chemiluminescence immunoassay method. Given their excellent signal amplification ability, the proposed MOF@AuNPs could serve as an ideal ICA label for rapid and sensitive detection of disease biomarkers. Graphical abstract.

Structure of water confined between two parallel graphene plates.

We study, in this paper, the physical properties of water confined between two parallel graphene plates with different slit widths to understand the effects of confinement on the water structure and how bulk properties are reached as the water layer thickens. It was found that the microscopic structures of the interfacial liquid layer close to graphene vary with the slit width. Water tends to locate at the center of the six-membered ring of graphene planes to form triangular patterns, as found by others. The narrower the slit width is, the more pronounced this pattern is, except for the slit width of 9.5 Å, for which a well-defined two-layer structure of water forms. On the other hand, squared structures can be clearly seen in single snapshots at small (6.5 Å and 7.5 Å) but not large slit widths. Even at small slit widths, the square-like geometry is observed only when an average is taken for a short trajectory, and averaging over a long time yields a triangular pattern dictated by the graphene geometry. We estimate the length of time needed to observe two patterns, respectively. We also used the two-phase thermodynamic model to study the variation of entropy of confined water and found that at 8.5 Å, the entropy of confined water is larger than that of bulk water. The rotational entropy of confined water is higher than that of bulk water for all slit widths due to the reduction of the hydrogen bond in the confined space.

Effect of TiO2 nanoparticle aggregation on marine microalgae Isochrysis galbana.

TiO2 nanoparticles (NPs) could adversely impact aquatic ecosystems. However, the aggregation of these NPs could attenuate this effect. In this work, the biological effects of TiO2 NPs on a marine microalgae Isochrysis galbana were investigated. The aggregation kinetics of TiO2 NPs under different conditions was also investigated to determine and understand these effects. Results showed that, though TiO2 NPs had no obvious impact on the size and reproducibility of algal cells under testing conditions, they caused a negative effect on algal chlorophyll, which led to a reduction in photosynthesis. Furthermore, fast aggregation of TiO2 NPs occurred under all conditions, especially at the pH close to the pHzpc. Increasing ionic strength and NP concentration also enhanced the aggregation rate. The aggregation and the following sedimentation of TiO2 NPs reduced their adverse effects on I. galbana.

[Effect of thalidomide in a mouse model of paraquat-induced acute lung injury and the underlying mechanisms].

OBJECTIVE: To investigate the effects of thalidomide in a mouse model of paraquat-induced acute lung injury and the mechanisms underlying the properties of thalidomide. METHODS: Male ICR mice were randomly allocated into four groups: nomal control group (n = 30), thalidomide control group (n = 30), paraquat poisioning group (n = 30) and thalidomide treatment group (n = 90). Mice were sacrificed at 1d, 3d and 7d after paraquat poisioning. The level of (MDA) malondialdehyde, Superoxidedi-smutase (SOD) and glutathione (GSH) in the lung tissue were measuerd by chemical colorimetry. The expression of Nrf2 mRNA was determined by RT-PCR; Nuclear protein Nrf2 was abserved by Western blotting; Pathological changes of lung tissue were observed under light microscope by HE stain; the lung apoptosis cells were detected by TUNEL. RESULTS: The levels of MDA, SOD and the expressions Nrf2 mRNA and protein Nrf2 in lung tissue were all markedly increased in mice of paraquat poisioning group than those in nomal group at 1 d, 3 d, 7 d. In contrast, the levels of GSH were decreaseel (P<0.05). Compared with paraquat poisioning group, the pulmonary SOD, Nrf2 mRNA and protein were increased and the lung wet dry ratio were all significantly decreased in mice of THD treatment group at 1 d, 3 d, 7 d (P<0.05). THD alleviated the pulmonary damage in the lightmicroscope at 3d after paraquat poisioning. The apoptosis index was markedly decreased in THD treatment groups comparing to paraquat piosioning group (P<0.05). CONCLUSIONS: Lipid peroxide damage was one of the mechanisms of paraquat poisioning, thalidomide could attenuate paraquat-induced acute lung injury and its mechanism may be activating the Nrf2-ARE signaling pathway to protect mouse from Lipid peroxide damage.

Quantum Computation of Conical Intersections on a Programmable Superconducting Quantum Processor.

Conical intersections (CIs) are pivotal in many photochemical processes. Traditional quantum chemistry methods, such as the state-average multiconfigurational methods, face computational hurdles in solving the electronic Schrödinger equation within the active space on classical computers. While quantum computing offers a potential solution, its feasibility in studying CIs, particularly on real quantum hardware, remains largely unexplored. Here, we present the first successful realization of a hybrid quantum-classical state-average complete active space self-consistent field method based on the variational quantum eigensolver (VQE-SA-CASSCF) on a superconducting quantum processor. This approach is applied to investigate CIs in two prototypical systems─ethylene (C2H4) and triatomic hydrogen (H3). We illustrate that VQE-SA-CASSCF, coupled with ongoing hardware and algorithmic enhancements, can lead to a correct description of CIs on existing quantum devices. These results lay the groundwork for exploring the potential of quantum computing to study CIs in more complex systems in the future.

Cellulose-based yellow-green emitting carbon dots with large Stokes shift as effective "turn off-on" fluorescence platforms for Cr (VI) and AA dual efficacy detection.

BACKGROUND: Hexavalent chromium (Cr (VI)) is highly carcinogenic to humans. Ascorbic acid (AA) deficiency can be hazardous to health. And the dual-effect fluorescence detection of them is an important research topic. Carbon dots (CDs) based on cellulose are excellent candidates for the fluorescence probes due to their low cost and environmental friendliness. But most of them exhibit shortwave emission, small Stokes shift and poor fluorescence performance, all of which limit their use. Therefore, there is an urgent need for cellulose CDs with longer emission wavelengths and larger Stokes shifts in dual-effect fluorescence detection of Cr (VI) and AA. RESULTS: Under optimal conditions (180 °C, 12 h), we prepared cellulose-based nitrogen-doped carbon dots (N-CDs) by a simple one-step hydrothermal process, which display longer emission wavelengths (ex: 370 nm, em: 510 nm), larger Stokes shifts (140 nm) and high fluorescence quantum yield (QY: 19.27 %). The continuous "turn-off" and "turn-off-on" fluorescence detection platforms were constructed based on the internal filtering effect (IFE) between Cr6+ and N-CDs, and Cr6+ reduced to Cr3+ by AA at pH = 6. The platform has been successfully simultaneous detect Cr (VI) and AA with a wide range of 0.01-40 µM and 0.1-100 µM. And the lowest limits of detection (LOD) are 0.0303 µM and 0.072 µM, respectively. In the presence of some other metals, non-metal ions and water-soluble acids in the fruits, this fluorescent platform can demonstrate a high level of interference immunity. SIGNIFICANCE AND NOVELTY: This represents the first yellow-green cellulose-based N-CDs with large Stokes shift for dual-effect detection of Cr (VI) and AA in real water samples and fresh fruits. The fluorescence detection platform has the advantage of low volume detection. Less than 2 mL of sample is required for testing and results are available in <5 min. This method is rare and supply a novel idea for the quantitative monitoring of Cr (VI) and AA.

Bioactive compounds from dichloromethane extract of Artemisia rupestris L. alleviates CCl4/ConA-induced acute liver injury by inhibiting PI3K-AKT pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia rupestris L. (AR) is a traditional medicinal herb commonly used in the Uyghurs and Kazakhs; it was first documented in the Supplement to Compendium of Materia Medica written by Zhao Xuemin in the Qing Dynasty of China and is used clinically to treat colds, hepatitis, and allergic diseases. AIM OF THE STUDY: The material basis and mechanisms of AR in acute liver injury (ALI) remain unclear. The purpose of this study was to reveal the possible active components involved in liver protection in AR and to preliminarily explore their pharmacological mechanisms. MATERIALS AND METHODS: The chemical composition of the ethanolic extract (ARA) was identified by UPLC-Q-Exactive-MS/MS and confirmed by 32 reference standards. The pharmacodynamic results were utilized to screen the active part within the ARA that contribute to the amelioration of CCl4/ConA-induced ALI. The main active components and core targets were predicted by network pharmacology and verified by molecular docking combined with qPCR and Western blotting. RESULTS: A total of 131 chemical components were identified in the ARA. The extraction parts of ARA had different therapeutic effects on ALI, among which the dichloromethane extract (ARA-D), which might constitute the main effective fraction of ARA, had significant anti-ALI effects. The network pharmacology results showed that targets including PIK3R1, AKT1, and EGFR, as well as 7 compounds, such as artemetin, vitexicarpin and rupestonic acid may play pivotal roles in treating CCl4/ConA-induced ALI. GO and KEGG pathway enrichment analyses revealed that the PI3K-AKT signaling pathway was the main pathway involved. In each model, ARA-D dose-dependently reduced the increase in ALT levels. High-dose ARA-D markedly decreased ALT activity from 196.79 ± 24.82 to 66.37 ± 16.19 U/L in the CCl4 model group and from 178.00 ± 28.39 to 50.67 ± 7.39 U/L in the ConA model group. Further studies revealed that ARA-D significantly inhibited TNF-α, IL-1ß, and IL-6 expression and inhibited the protein expression of PI3K, p-PI3K, and p-AKT in CCl4/ConA-induced ALI. CONCLUSION: ARA-D exhibits protective effects against ALI induced by CCl4/ConA, potentially through inhibition of the PI3K-AKT signaling pathway. These findings may help to determine the material basis and mechanisms of action of ARA-D for liver protection and provide ideas for future comprehensive studies.

Concentrations and controls of dissolved inorganic carbon in Arctic summer sea ice and adjacent surface seawaters.

The carbonate chemistry of sea ice plays a critical role in global ocean carbon cycles, particularly in polar regions which are subject to significant climate change-induced sea ice variation. However, less is known about the interaction of carbonate system between sea ice and its adjacent seawaters due to sparse sampling and disparities in reported results. Here we provide an insight into this issue by collecting and measuring dissolved inorganic carbon (DIC) and associated environmental parameters in Arctic sea ice during a cruise in the summer of 2014. Our observations show that DIC in Arctic summer sea ice has a mean concentration of 463.3 ± 213.0 µmol/kg and appears to be controlled mainly by the fraction of brine water in the ice. The low Chl a and nutrients content in sea ice indicate minor contribution of biological uptake to sea-ice DIC in the western Arctic Ocean. The DIC concentration in surface water (<100 m depth) decreased from a mean of 2108.3 ± 45.4 µmol/kg in 1994 to a mean of 2052.4 ± 98.6 µmol/kg in 2014, due to the enhanced sea ice melting that dilutes the DIC concentrations of surrounding seawaters.

High capacity and fast removal of Cr(vi) by alkali lignin-based poly(tetraethylene pentamine-pyrogallol) sorbent.

In this work, a novel alkali lignin-based adsorption material, alkali lignin-based poly(tetraethylene pentamine-pyrogallol) (AL-PTAP), was prepared using a Mannich reaction and catechol-amine reaction for removal of Cr(vi). It was characterized by thermogravimetric analysis (TGA), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS). The effects of tetraethylene pentamine (TEPA) dosage, pyrogallol (PL) dosage, contact time, pH, temperature and other factors on the adsorption behavior of the adsorbent were systematically investigated. These experimental data show that the adsorption behavior conforms to the pseudo-second-order kinetic model and the Langmuir isotherm model. The maximum adsorption capacity is 769.2 mg g-1 at 303 K, which is much higher than that of alkali lignin (AL). AL-PTAP can achieve a removal rate of almost 100% for Cr(vi) solutions with a concentration of less than 90 mg L-1 at 1 min. Furthermore, the toxic Cr(vi) is partly reduced to nontoxic Cr(iii) during the adsorption process. Therefore, AL-PTAP is a fast and efficient alkali lignin-based adsorbent, which is expected to improve the utilization value of alkali lignin in Cr(vi) wastewater treatment.

The application of a continuous partnership-based birth plan in China: A randomized controlled trial.

BACKGROUND: The cesarean section rate is as high as 36.7% in China, much higher than the average cesarean section rate of 27% in Asia. With the implementation of the two-children and three-children policy, the primipara with cesarean will also face the choice of repeated or even multiple cesareans, which will increase the risk of maternal perinatal mortality and serious fetal pulmonary morbidity. To reduce the cesarean section rate, a series of midwifery service measures such as the birth plan have been taken in China and it has played a certain role in improving the birth outcome and maternal birth experience. However, the areas carrying out birth plan are often economically developed with advanced medical conditions. the application effect of birth plan in economically underdeveloped areas with limited medical conditions in China is unknown. OBJECTIVE: To evaluate the effects of a continuous partnership-based birth plan on local women's birth outcomes and experience in Haikou which is an economically underdeveloped city in China. DESIGN: A randomized controlled trial study design was used. PARTICIPANTS: 90 primiparous women who received pregnancy service from the obstetrics clinic of one of tertiary hospitals in Haikou city, Hainan Province between July 2020 and December 2020 and planned to give birth in this hospital were recruited. METHODS: After eligibility was determined, consents obtained and baseline surveys completed, 90 participants were randomly allocated to study groups with concealed opaque envelopes by a blinded research assistant and each group were 45 participants. Participants in control group received routine obstetric health service and nursing care, while participants in the experimental group received the continuous partnership service of midwives on the basis of routine care. At the same time, the birth plan was formulated and implemented, and the relevant indicators were recorded and analyzed during and after birth, including cesarean section rate, non-medical indication cesarean section rate, oxytocin use rate, perineal lateral resection rate and anxiety degree. RESULTS: The cesarean rate in the experiment and control groups were 20.45% and 57.14%, of which the non-medical indication cesarean rate in the experiment and control groups were 22.22% and 50.00%, respectively, whereby the difference of cesarean rate and nonmedically indicated cesarean section rate between the groups was statistically significant (χ2 = 12.231, p < 0.001;χ2 = 9.101, p = 0.003). Besides, the differences in anxiety degree, neonatal NICU transfer rate and satisfaction of birth between the two groups were statistically significant (p < 0.05). While there was no significant difference in oxytocin use rate, perineal lateral resection rate, neonatal 1-min and 5-min Alzheimer's score between the two groups (P > 0.05). CONCLUSION: The birth plan based on continuous partnership can reduce medical intervention, improve birth outcomes, reduce anxiety and optimize maternal birth experience of women, which is worthy of promotion in economically underdeveloped areas of China.

STAG2 Regulates Homologous Recombination Repair and Sensitivity to ATM Inhibition.

Stromal antigen 2 (STAG2), a subunit of the cohesin complex, is recurrently mutated in various tumors. However, the role of STAG2 in DNA repair and its therapeutic implications are largely unknown. Here it is reported that knockout of STAG2 results in increased double-stranded breaks (DSBs) and chromosomal aberrations by reducing homologous recombination (HR) repair, and confers hypersensitivity to inhibitors of ataxia telangiectasia mutated (ATMi), Poly ADP Ribose Polymerase (PARPi), or the combination of both. Of note, the impaired HR by STAG2-deficiency is mainly attributed to the restored expression of KMT5A, which in turn methylates H4K20 (H4K20me0) to H4K20me1 and thereby decreases the recruitment of BRCA1-BARD1 to chromatin. Importantly, STAG2 expression correlates with poor prognosis of cancer patients. STAG2 is identified as an important regulator of HR and a potential therapeutic strategy for STAG2-mutant tumors is elucidated.

A systematic review and meta-analysis of the efficacy of aerobic exercise combined with resistance training on maintenance hemodialysis patients.

BACKGROUND: Chronic kidney disease (CKD) is a life-threatening illness that causes significant pain to patients, this serious impact on patient's physical fitness and quality of life. Previous studies have found that exercise training has a positive impact on improving CKD patients' symptoms. In order to improve patients' physical function and quality of life, this meta-analysis aimed to evaluate the application value of aerobic exercise combined with resistance training in maintenance hemodialysis (MHD) patients. METHODS: A computer search was conducted of PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu databases. The search keywords were: "chronic kidney disease", "end-stage renal disease", "hemodialysis", "maintenance hemodialysis", "exercise", "aerobic exercise", "resistance exercise", "combined exercise", and "physical exercise". Included studies should meet the following criteria, the study population is MHD patients, the intervention is aerobic exercise combined with resistance training, and a randomized controlled study with clearly documented outcome indicators. The Cochrane risk-of-bias tool was used to evaluate the quality of the included studies, and the meta-analysis was performed by RevMan 5.20 software (Cochrane Collaboration). RESULTS: A total of seven articles met the inclusion criteria. The included studies were assessed for risk of bias and met the inclusion criteria. The results of the meta-analysis showed significant differences between patients who received aerobic exercise combined with resistance training and control patients (the rest treatment was same as the study group) in the urea clearance index [mean difference (MD) =0.16, 95% confidence interval (CI): 0.10, 0.21], mental health (MD =7.54, 95% CI: 2.74, 12.35) and social functioning (MD =9.98, 95% CI: 1.52, 18.44). However, there was no significant difference in physical functioning between the two groups (MD =1.26, 95% CI: -1.20, 3.71). DISCUSSION: Although aerobic exercise combined with resistance training did not improve the physical functioning of MHD patients, it improved their urea clearance, mental health, and social functioning and positively affected their quality of life, risk of bias should also be considered. In the future, multi-center studies with larger samples should be used to explore the effects of aerobic exercise combined with resistance training on MHD patients.

Steroid receptor coactivator-1: The central intermediator linking multiple signals and functions in the brain and spinal cord.

The effects of steroid hormones are believed to be mediated by their nuclear receptors (NRs). The p160 coactivator family, including steroid receptor coactivator-1 (SRC-1), 2 and 3, has been shown to physically interact with NRs to enhance their transactivational activities. Among which SRC-1 has been predominantly localized in the central nervous system including brain and spinal cord. It is not only localized in neurons but also detectable in neuroglial cells (mainly localized in the nuclei but also detectable in the extra-nuclear components). Although the expression of SRC-1 is regulated by many steroids, it is also regulated by some non-steroidal factors such as injury, sound and light. Functionally, SRC-1 has been implied in normal function such as development and ageing, learning and memory, central regulation on reproductive behaviors, motor and food intake. Pathologically, SRC-1 may play a role in the regulation of neuropsychiatric disorders (including stress, depression, anxiety, and autism spectrum disorder), metabolite homeostasis and obesity as well as tumorigenesis. Under most conditions, the related mechanisms are far from elucidation; although it may regulate spatial memory through Rictor/mTORC2-actin polymerization related synaptic plasticity. Several inhibitors and stimulator of SRC-1 have shown anti-cancer potentials, but whether these small molecules could be used to modulate ageing and central disorder related neuropathology remain unclear. Therefore, to elucidate when and how SRC-1 is turned on and off under different stimuli is very interesting and great challenge for neuroscientists.

Protective Effect of Natural Antioxidants on Reducing Cisplatin-Induced Nephrotoxicity.

The clinical application of cisplatin is limited by its adverse events, of which nephrotoxicity is the most commonly observed. In a cisplatin-induced pathological response, oxidative stress is one of the upstream reactions which inflicts different degrees of damages to the intracellular material components. Reactive oxygen species (ROS) are also one of the early signaling molecules that subsequently undergo a series of pathological reactions, such as apoptosis and necrosis. This review summarizes the mechanism of intracellular ROS generation induced by cisplatin, mainly from the consumption of endogenous antioxidants, destruction of antioxidant enzymes, induction of mitochondrial crosstalk between the endoplasmic reticulum by ROS and Ca2+, and destruction of the cytochrome P450 (CYP) system in the endoplasmic reticulum, all of which result in excessive accumulation of intracellular ROS and oxidative stress. In addition, studies demonstrated that natural antioxidants can protect against the cisplatin-induced nephrotoxicity, by reducing or even eliminating excess free radicals and also affecting other nonredox pathways. Therefore, this review on the one hand provides theoretical support for the research and clinical application of natural antioxidants and on the other hand provides a new entry point for the detailed mechanism of cisplatin nephrotoxicity, which may lay a solid foundation for the future clinical use of cisplatin.

Design of co-continuous structure of cellulose/PAA-based alkaline solid polyelectrolyte for flexible zinc-air battery.

In order to prepare high ionic conductivity and robust mechanical properties of alkaline solid polyelectrolyte (ASPE) for applications in flexible wearable devices, a co-continuous structure membrane was designed using in-situ polymerization to introduce cross-linked polyacrylic acid (N-PAA) into the cellulose network constructed by regenerated degreasing cotton (RDC). The resultant ASPE membrane showed high ionic conductivity (430 mS·cm-1 at 25 °C), strong mechanical properties, and excellent alkaline stabilities, proving the viability of cellulose for use in energy storage systems. Surprisingly, the sandwich-shaped zinc-air battery assembled using RDC/N-PAA/KOH membranes as electrolytes exhibits superior values of cycling stability, discharge time, specific capacity (731.5 mAh·g-1), peak power density (40.25 mW·cm-2), and mechanical flexibility. Even under bending conditions, the zinc-air batteries still possess stable energy supply performance, suggesting this novel solid polyelectrolyte has promising application for wearable technology.

ZIF-8 derived porous carbon to mitigate shuttle effect for high performance aqueous zinc-iodine batteries.

Rechargeable aqueous zinc-iodine batteries (ZIBs) with low environmental impacts and abundant natural reserves have emerged as promising electrochemical energy storage devices. However, the shuttle effect and low conductivity of the iodine species cause poor electrochemical performance and hinder their practical application. Herein, we propose a ZIF-8 derived porous carbon (ZPC) for iodine species immobilization in ZIBs. The rich porous structure and highly conductive framework of ZPC provide efficient iodine loading and allow the fast transmission of electrons. In addition, the presence of N, Zn and ZnO in the carbon framework can build chemical anchoring with the iodine species to mitigate the shuttle effect. Thus, the ZPC/I2 cathode exhibits a reversible capacity of 156 mAh g-1 after 100 cycles at 100 mA g-1 and a long-term stability of 1000 cycles at a high rate. This study will open a new paradigm for devolving highly reversible ZIBs.

Integrating Network Pharmacology and In Vivo Model to Investigate the Mechanism of Biheimaer in the Treatment of Functional Dyspepsia.

Objective: Biheimaer (BHM) is a hospital formulation for clinical treatment of dyspepsia and acid reflux, based on Compatibility Theory of Traditional Chinese Medicine. This study anticipated to elucidate the molecular mechanism of BHM against Functional dyspepsia via combined network pharmacology prediction with experimental verification. Methods: Based on network pharmacology, the potential active components and targets of BHM in the treatment of functional dyspepsia were explored by prediction and molecular docking technology. The results of protein-protein interaction analysis, functional annotation, and pathway enrichment analysis further refined the main targets and pathways. The molecular mechanism of BHM improving functional dyspepsia mice induced by L-arginine + atropine was verified on the basis of network pharmacology. Results: In this study, 183 effective compounds were screened from BHM; moreover, 1007 compound-related predicted targets and 156 functional dyspepsia-related targets were found. The results of enrichment analysis and in vivo experiments showed that BHM could regulate intestinal smooth muscle contraction to play a therapeutic role in functional dyspepsia by reducing the expression of NOS3, SERT, TRPV1, and inhibiting the inflammatory cytokine (IL-1ß, TNF-α) to intervene the inflammatory response in mice. Conclusions: This study revealed the molecular biological mechanisms of the Traditional Chinese Medicine formulation of BHM in functional dyspepsia by network pharmacology and experimental verification, meanwhile provided scientific support for subsequent clinical medication.