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Background: Colorectal cancer (CRC) is a considerable global health issue. Dioscin, a compound found in several medicinal plants, has shown potential anticancer effects., Aim: To find the relationship between CRC cells (HCT116) and diosgenin and clarified their mechanisms of action., Methods: CRC cell line HCT116 was cultured by dividing cells into control and dioscin groups (dioscin + Jagged 1 group; Jagged 1 group, 5 μg/mL; and dioscin group, 2.5 μg/mL). The dioscin groups were given different concentrations of dioscin. Cell Counting Kit-8 was chosen for testing cell viability in different groups. Flow cytometry was established to undiscover the apoptosis rate of human liver cancer cell line 11. Real-time PCR as well as Western blot analyses were applied to reveal the expression levels of caspase-3, Notch, and other proteins. Transwell and scratch experiments were conducted to assess cell migration and invasion abilities., Results: This study indicated that dioscin restricted the growth of HCT116 cells, boosted cell apoptosis, and rose the Bax / Bcl-2 ratio as well as the expression of Caspase-3 . Dioscin also inhibited physiological activities, for instance cell migration, and significantly reduced the expression levels of proteins for instance Notch1 ( P < 0.05). Dioscin partially reversed the effects of Jagged 1., Conclusion: Dioscin exerts a certain inhibitory effect on HCT116, and its mechanism of action may be linked, with the inhibition of the Notch1 signaling pathway., Competing Interests: Conflict-of-interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Depression is a pervasive and often undetected mental health condition, which poses significant challenges for early diagnosis due to its silent and subtle nature. To evaluate exhaled volatile organic compounds (VOCs) as non-invasive biomarkers for the detection of depression using a virtual surface acoustic wave sensors array (VSAW-SA). A total of 245 participants were recruited from the Hangzhou Community Health Service Center, including 38 individuals diagnosed with depression and 207 control subjects. Breath samples were collected from all participants and subjected to analysis using VSAW-SA. Univariate and multivariate analyses were employed to assess the relationship between VOCs and depression. The findings revealed that the responses of virtual sensor ID 14, 44, 59, and 176, which corresponded respectively to ethanol, trichloroethylene or isoleucine, octanoic acid or lysine, and an unidentified compound, were sensitive to depression. Taking into account potential confounders, these sensor responses were utilized to calculate a depression detection indicator. It has a sensitivity of 81.6% and a specificity of 81.6%, with an area under the curve of 0.870 (95% CI = 0.816-0.923). Conclusions: exhaled VOCs as non-invasive biomarkers of depression could be detected by a VSAW-SA. Large-scale cohort studies should be conducted to confirm the potential ability of the VSAW-SA to diagnose depression., (Creative Commons Attribution license.)

Although many researchers of Parkinson's disease (PD) have shifted their focus from the central nervous system (CNS) to the peripheral blood, a significant knowledge gap remains between PD severity and the peripheral immune response. In the current study, we aimed to map the peripheral immunity atlas in peripheral blood mononuclear cells (PBMCs) from PD patients and healthy controls using single-cell RNA sequencing (scRNA-seq). Our study employed scRNA-seq analysis to map the peripheral immunity atlas in PD by profiling PBMCs from PD-Early, PD-Late patients and matched controls. By enlarging the blood sample size, we validated the roles of NK cells in numerous immune-related biological processes. We also detected the infiltration of NK cells into the cerebral motor cortex as the disease progressed, using human brain sections, and elucidated the communication between the periphery and CNS and its implications for PD. As a result, cell subpopulation atlases in PBMCs from PD patients and healthy controls along with differentially expressed genes in NK cells were identified by scRNA-seq analysis, representing 6 major immune cell subsets among which NK cells declined in the progression of PD. We further validated NK cell reduction in increasing samples and found that they participated in numerous immune-related biological processes and infiltration into the cerebral motor cortex as the disease proceeded, evidencingd the close communication between the peripheral immune response and CNS. Strikingly, XCL2 positively correlated with PD severity, with good predictive performance of PD and specific expression in subclusters C2 and C5 of NK cells. All these findings delineated the critical role of peripheral immune response mediated by NK cells in the pathogenesis of PD. NK cell-specific XCL2 could be used as a diagnostic marker for treating PD. The indispensable function of NK cells and NK cell-specific molecular biomarkers highlighted the implication of the peripheral immune response in PD progression. Trial registration: ChiCTR, ChiCTR1900023975. Registered 20 June 2019 - Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=31035 ., (© 2024. The Author(s).)

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 Cr 6+ and N-CDs, and Cr 6+ reduced to Cr 3+ 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Hemorrhagic varicella (HV) is a particular form of chicken pox.,with high mortality in adults. This form of the disease is rare, to date, approximately 4 cases have been reported. Occasional cases of HV have been documented in adults with hematologic disorders or other diseases. While there is one reported case of simultaneous reactivation of cytomegalovirus in an adult with chickenpox, there is a lack of information regarding changes in liver function indicators for such patients. This is unfortunate, as CMV reactivation can further exacerbate liver failure and increase mortality. In this report, we present a case of hemorrhagic varicella reactivation with cytomegalovirus and provide some relevant discussions., Case Presentation: We present the case of a 25-year-old male with HV, who had a history of nephrotic syndrome generally controlled with orally administered prednisone at a dosage of 50 mg per day for two months. The patient arrived at the emergency room with complaints of abdominal pain and the presence of hemorrhagic vesicles on his body for the past 3 days. Despite medical evaluation, a clear diagnosis was not immediately determined. Upon admission, the leukocyte count was recorded as 20.96 × 10 9 /L on the first day, leading to the initiation of broad-spectrum antibiotic treatment. Despite the general interpretation that a positive IgG and a negative IgM indicate a previous infection, the patient's extraordinarily elevated IgG levels, coupled with a markedly increased CMV DNA quantification, prompted us to suspect a reactivation of the CMV virus. In light of these findings, we opted for the intravenous administration of ganciclovir as part of the treatment strategy. Unfortunately,,the patient succumbed to rapidly worsening symptoms and passed away. Within one week of the patient's demise, chickenpox gradually developed in the medical staff who had been in contact with him. In such instances, we speculate that the patient's diagnosis should be classified as a rare case of hemorrhagic varicella., Conclusion: Swift identification and timely administration of suitable treatment for adult HV are imperative to enhance prognosis., (© 2024. The Author(s).)

Pulmonary hypertension (PH) is a severe clinical syndrome with pulmonary vascular remodeling and poor long-term prognosis. Neurotensin receptor 1 (Ntsr1), serve as one of the G protein-coupled receptors (GPCRs), implicates in various biological processes, but the potential effects of Ntsr1 in PH development are unclear. The Sugen/Hypoxia (SuHx) or monocrotaline (MCT) induced rat PH model was used in our study and the PH rats showed aggravated pulmonary artery remodeling and increased right ventricular systolic pressure (RVSP). Our results revealed that Ntsr1 induced endoplasmic reticulum (ER) stress response via ATF6 activation contributed to the development of PH. Moreover, RNA-sequencing (RNA-seq) and phosphoproteomics were performed and the Ntsr1-JAK2-STAT3-thrombospondin 1 (Thbs1)-ATF6 signaling was distinguished as the key pathway. In vitro, pulmonary artery smooth muscle cells (PASMCs) under hypoxia condition showed enhanced proliferation and migration properties, which could be inhibited by Ntsr1 knockdown, JAK2 inhibitor (Fedratinib) treatment, STAT3 inhibitior (Stattic) treatment, Thbs1 knockdown or ATF6 knockdown. In addition, adeno-associated virus 1 (AAV1) were used to knockdown the expression of Ntsr1, Thbs1 or ATF6 in rats and reversed the phenotype of PH. In summary, our results reveal that Ntsr1-JAK2-STAT3-Thbs1 pathway can induce enhanced ER stress via ATF6 activation and increased PASMC proliferation and migration capacities, which can be mechanism of the pulmonary artery remodeling and PH. Targeting Ntsr1 might be a novel therapeutic strategy to ameliorate PH., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest. All authors have carefully reviewed and complied with the journal's authorship agreement., (Copyright © 2024. Published by Elsevier Inc.)

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, and recent epidemiological studies suggested type 2 diabetes mellitus (T2DM) is an independent risk factor for the development of AF. Zinc finger and BTB (broad-complex, tram-track and bric-a-brac) domain containing 16 (Zbtb16) serve as transcriptional factors to regulate many biological processes. However, the potential effects of Zbtb16 in AF under T2DM condition remain unclear. Here, we reported that db/db mice displayed higher AF vulnerability and Zbtb16 was identified as the most significantly enriched gene by RNA sequencing (RNA-seq) analysis in atrium. In addition, thioredoxin interacting protein (Txnip) was distinguished as the key downstream gene of Zbtb16 by Cleavage Under Targets and Tagmentation (CUT&Tag) assay. Mechanistically, increased Txnip combined with thioredoxin 2 (Trx2) in mitochondrion induced excess reactive oxygen species (ROS) release, calcium/calmodulin-dependent protein kinase II (CaMKII) overactivation, and spontaneous Ca 2+ waves (SCWs) occurrence, which could be inhibited through atrial-specific knockdown (KD) of Zbtb16 or Txnip by adeno-associated virus 9 (AAV9) or Mito-TEMPO treatment. High glucose (HG)-treated HL-1 cells were used to mimic the setting of diabetic in vitro. Zbtb16-Txnip-Trx2 signaling-induced excess ROS release and CaMKII activation were also verified in HL-1 cells under HG condition. Furthermore, atrial-specific Zbtb16 or Txnip-KD reduced incidence and duration of AF in db/db mice. Altogether, we demonstrated that interrupting Zbtb16-Txnip-Trx2 signaling in atrium could decrease AF susceptibility via reducing ROS release and CaMKII activation in the setting of T2DM., (© 2024. The Author(s).)

Background: The relationship between fibrosis-4 (FIB-4) index and all-cause mortality in critically ill patients with alcohol use disorder (AUD) is unclear. The present study aimed to investigate the predictive ability of FIB-4 for all-cause mortality in critically ill AUD patients and the association between them., Methods: A total of 2528 AUD patients were included using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. FIB-4 was calculated for each patient using the existing formula. The patients were equally divided into four groups based on the quartiles of FIB-4. Multivariate logistic regression and Cox proportional hazard model were used to evaluate the association of FIB-4 with in-hospital mortality, 28-day mortality and 1-year mortality. Kaplan-Meier curves were used to analyse the incidence of 28-day mortality among four groups., Results: FIB-4 was positively associated with 28-day mortality of AUD patients with hazard ratio (HR) of 1.354 [95% confidence interval (CI) 1.192-1.538]. There were similar trends in the in-hospital mortality [odds ratio (OR): 1.440, 95% CI (1.239-1.674)] and 1-year mortality [HR: 1.325, 95% CI (1.178-1.490)]., Conclusion: Increased FIB-4 is associated with greater in-hospital mortality, 28-day mortality and 1-year mortality in critically ill AUD patients., (© 2023 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

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., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Objective: To investigate the effect of vitamin D3 on mild cognitive impairment in type 2 diabetic mice and explore its possible mechanism., Methods: Male db/db mice were randomly divided into 4 groups: the diabetes mellitus (DM) group, the low dose [250 IU/(kg·d)], medium dose [500 IU/ (kg·d)] and high dose [1 000 IU/(kg·d)] vitamin D3 intervention groups. The db/m mice were enrolled as the normal control group. The mice in vitamin D3 groups were gavaged with corresponding concentration of vitamin D3 in corn oil, and the mice in the normal control group and the DM group were gavaged with corn oil. After being fed for 16 weeks, fasting blood glucose of mice in each group was measured at the end of 0, 4, 8 and 16 weeks, and the new object recognition experiment was conducted at the end of 16 weeks. At the end of the experiment, the hippocampi and cortices of mice in each group were collected, and the concentration of 5-hydroxytryptamine (5-HT) and interleukin-18 (IL-18) in the hippocampal tissues of mice in each group were determined by enzyme linked immunosorbent assay (ELISA). Immunohistochemical staining was used to observe the expression of nucleotide binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) in the hippocampal tissues of the mice., Results: Compared with the normal control group, the fasting blood glucose of mice in DM group was significantly increased ( P < 0.01). The exploration and discrimination index (DI) in the new object recognition experiment were significantly decreased ( P < 0.05). The concentrations of 5-HT in the hippocampal tissues of mice were significantly decreased ( P < 0.01). The concentrations of IL-18 in cortical tissues of mice were significantly increased ( P < 0.01) and the positive expression of NLRP3 in the hippocampal tissues was higher. However, compared with the DM group, the fasting blood glucose of mice was significantly decreased in the medium and high dose vitamin D3 groups at the end of 8 and 16 weeks ( P < 0.05 or P < 0.01). The exploration and DI of mice in the new object recognition experiment were significantly increased in high dose vitamin D3 group ( P < 0.05). The concentrations of 5-HT in hippocampal tissues were significantly increased ( P < 0.01) and the concentrations of IL-18 in cortical tissues were significantly decreased in the medium and high dose vitamin D3 groups ( P < 0.01). The positive expression of NLRP3 in hippocampal tissues was reduced in all the vitamin D3 groups., Conclusion: Vitamin D3 might reduce the inflammatory response by inhibiting the activity of NLRP3, and thus ameliorating mild cognitive impairment in type 2 diabetic mice.

As an important driving force, introgression plays an essential role in shaping the evolution of plant species. However, knowledge concerning how introgression affects plant evolution in agroecosystems with strong human influences is still limited. To generate such knowledge, we used InDel (insertion/deletion) molecular fingerprints to determine the level of introgression from japonica rice cultivars into the indica type of weedy rice. We also analyzed the impact of crop-to-weed introgression on the genetic differentiation and diversity of weedy rice, using InDel (insertion/deletion) and SSR (simple sequence repeat) molecular fingerprints. Results based on the STRUCTURE analysis indicated an evident admixture of some weedy rice samples with indica and japonica components, suggesting different levels of introgression from japonica rice cultivars to the indica type of weedy rice. The principal coordinate analyses indicated indica - japonica genetic differentiation among weedy rice samples, which was positively correlated with the introgression of japonica -specific alleles from the rice cultivars. In addition, increased crop-to-weed introgression formed a parabola pattern of dynamic genetic diversity in weedy rice. Our findings based on this case study provide evidence that human activities, such as the frequent change in crop varieties, can strongly influence weed evolution by altering genetic differentiation and genetic diversity through crop-weed introgression in agroecosystems.

High-temperature body-centered cubic (BCC) γ-U is effectively stablized by γ-(U,Zr) alloys that also make it feasible to use it as a nuclear fuel. However, relatively little research has focused on γ-(U,Zr) alloys due to their instability at room temperature. The effect of Zr composition on its mechanical properties is not clear yet. Herein, we perform molecular dynamics simulations to investigate the mechanical and dynamical stabilities of γ-(U,Zr) alloys under high temperatures, and we calculate the corresponding lattice constants, various elastic moduli, Vickers hardness, Debye temperature, and dynamical structure factor. The results showed that γ-U, β-Zr, and γ-(U,Zr) are all mechanically and dynamically stable at 1200 K, which is in good agreement with the previously reported high-temperature phase diagram of U-Zr alloys. We found that the alloying treatment on γ-U with Zr can effectively improve its mechanical strength and melting points, such as Vickers hardness and Debye temperature, making it more suitable for nuclear reactors. Furthermore, the Zr concentrations in γ-(U,Zr) alloys have an excellent effect on these properties. In addition, the dynamical structure factor reveals that γ-U shows different structural features after alloying with Zr. The present simulation data and insights could be significant for understanding the structures and properties of UZr alloy under high temperatures.

Members of the GAPDH family play important roles in plant growth and development, as well as in stress responses. Our aim was to identify stress resistance genes through systematic analysis of the GAPDH family in watermelon. This could not only provide genetic resources for stress resistance breeding, but also form a basis for the study of plant stress resistance mechanisms. Eight GAPDHs representing four types of plant GAPDH in watermelon were identified (ClGAPA/B, ClGAPC1-3, ClGAPCp1-2 and ClGAPN). A comprehensive analysis of physicochemical properties, chromosome distribution, evolutionary relationships, exon-intron structure and conserved motifs of watermelon GAPDHs was performed using bioinformatics. Expression characteristics were assessed by RT-qPCR. Based on RT-qPCR results, ClGAPC2 was screened as a candidate for subcellular localization analysis and functional verification in Arabidopsis thaliana. Eight GAPDHs were classified into four subfamilies. GAPDHs in each subgroup were generally conserved and shared similarities in structure and conserved motifs. ClGAPDHs had notable tissue specificity and different expression patterns in response to H 2 O 2 , chilling, salt, osmotic stress, heat, salicylic acid, gibberellin, brassinosterol, ethylene and abscisic acid treatments. Three ClGAPC genes, especially ClGAPC2, were markedly induced by several treatments. ClGAPC2 was located in the nucleus and cytoplasm of tabacum epidermal cells. The ClGAPC2 transgenic Arabidopsis showed enhanced tolerance to salinity at the germination stage. We suggest that ClGAPC2 plays important roles in the adaptation of watermelon to salinity. Our findings provided candidate genes for further improving the salt tolerance of watermelon., (© 2022 German Society for Plant Sciences, Royal Botanical Society of the Netherlands.)

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 Ca 2+ , 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., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Jie Zhou et al.)

Microscopy by Achromatic X-rays With Emission of Laminar Light (MAXWELL) is a new X-ray/visible technique with attractive characteristics including isotropic resolution in all directions, large-volume imaging and high throughput. An ultrathin, laminar X-ray beam produced by a Wolter type I mirror irradiates the sample stimulating the emission of visible light by scintillating nanoparticles, captured by an optical system. Three-dimensional (3D) images are obtained by scanning the specimen with respect to the laminar beam. We implemented and tested the technique with a high-brightness undulator at SPring-8, demonstrating its validity for a variety of specimens. This work was performed under the Synchrotrons for Neuroscience-an Asia-Pacific Strategic Enterprise (SYNAPSE) collaboration., (© 2022. The Author(s).)

In this study, we aimed to evaluate the effect of Nobiletin (NOB) on the placenta of Sprague-Dawley (SD) rats that had undergone reduced uterine perfusion pressure (RUPP) surgery and to evaluate the safety of NOB intervention during pregnancy. The results showed that NOB alleviated placental hypoxia, attenuated placental cell apoptosis, and inhibited placental damage in RUPP rats. No side effect of NOB intervention during pregnancy was observed. BeWo cell lines with P53 knockdown were then constructed using lentiviral transfection, and the P53 signaling pathway was found to be essential for NOB to reduce hypoxia-induced apoptosis of the BeWo cell lines. In summary, NOB attenuated hypoxia-induced placental damage by regulating the P53 signaling pathway, and those findings may contribute some insights into the role of NOB in placental development and the prevention of placental-related diseases.

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 H 2 O 2 and catalase, plasma renin were assayed by commercial kits, and mRNAs of renin receptor, transforming growth factor-β (TGF-β) and cyclooxygenase-2 (COX-2) in the renal cortex, mRNAs of angiotensin receptor-1 (AT 1 R) and AT 2 R 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-β and COX-2, decreased production of H 2 O 2 and increased catalase activity in preglomerular arterioles and enhanced afferent arteriolar Ang II contractions. The latter were blunted by incubation with H 2 O 2 . The mRNAs of renal microvascular AT 1 R and AT 2 R 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.

Drug-metabolizing enzymes, particularly the cytochrome P450 (CYP450) monooxygenases, play a pivotal role in pharmacokinetics. CYP450 enzymes can be affected by various xenobiotic substrates, which will eventually be responsible for most metabolism-based herb-herb or herb-drug interactions, usually involving competition with another drug for the same enzyme binding site. Compounds from herbal or natural products are involved in many scenarios in the context of such interactions. These interactions are decisive both in drug discovery regarding the synergistic effects, and drug application regarding unwanted side effects. Herein, this review was conducted as a comprehensive compilation of the effects of herbal ingredients on CYP450 enzymes. Nearly 500 publications reporting botanicals' effects on CYP450s were collected and analyzed. The countries focusing on this topic were summarized, the identified herbal ingredients affecting enzyme activity of CYP450s, as well as methods identifying the inhibitory/inducing effects were reviewed. Inhibitory effects of botanicals on CYP450 enzymes may contribute to synergistic effects, such as herbal formulae/prescriptions, or lead to therapeutic failure, or even increase concentrations of conventional medicines causing serious adverse events. Conducting this review may help in metabolism-based drug combination discovery, and in the evaluation of the safety profile of natural products used therapeutically.

The valley degree of freedom of carriers in crystals is useful to process information and perform logic operations, and it is a key factor for valley application to realize valley polarization. Here, we propose a model that the valley polarization transition at different valley points (- K and K points) is produced by biaxial strain. Using first-principles calculations, we illustrate our idea with a concrete example of a Janus GdClF monolayer. The predicted GdClF monolayer is dynamically, mechanically and thermally stable, and is a ferromagnetic (FM) semiconductor with perpendicular magnetic anisotropy (PMA), valence band maximum (VBM) at valley points and a high Curie temperature ( T C ). Due to its intrinsic ferromagnetism and spin-orbit coupling (SOC), a spontaneous valley polarization will be induced, but the valley splitting is only -3.1 meV, which provides an opportunity to achieve valley polarization transition at different valley points by strain. In the considered strain range ( a / a 0 : 0.94-1.06), the strained GdClF monolayer always has an energy bandgap, strong FM coupling and PMA. The compressive strain is in favour of - K valley polarization, while the tensile strain is favorable for K valley polarization. The corresponding valley splittings at 0.96 and 1.04 strains are -44.5 meV and 29.4 meV, respectively, which are higher than the thermal energy at room temperature (25 meV). Due to its special Janus structure, both in-plane and out-of-plane piezoelectric polarizations can be observed. It is found that the direction of in-plane piezoelectric polarization can be overturned by strain, and the d 11 values at 0.96 and 1.04 strains are -1.37 pm V -1 and 2.05 pm V -1 , respectively. Our work paves the way to design ferrovalley materials for application in multifunctional valleytronic and piezoelectric devices by strain.