Natural Products for Pesticides Discovery: Structural Diversity Derivation and Biological Activities of Naphthoquinones Plumbagin and Juglone.

Plant diseases and insect pests seriously affect the yield and quality of crops and are difficult to control. Natural products are an important source for the discovery of new pesticides. In this work, naphthoquinones plumbagin and juglone were selected as parent structures, and a series of their derivatives were designed, synthesized and evaluated for their fungicidal activities, antiviral activities and insecticidal activities. We found that the naphthoquinones have broad-spectrum anti-fungal activities against 14 types of fungus for the first time. Some of the naphthoquinones showed higher fungicidal activities than pyrimethanil. Compounds I, I-1e and II-1a emerged as new anti-fungal lead compounds with excellent fungicidal activities (EC50 values: 11.35-17.70 µg/mL) against Cercospora, arachidicola Hori. Some compounds also displayed good to excellent antiviral activities against the tobacco mosaic virus (TMV). Compounds I-1f and II-1f showed similar level of anti-TMV activities with ribavirin, and could be used as new antiviral candidates. These compound also exhibited good to excellent insecticidal activities. Compounds II-1d and III-1c displayed a similar level of insecticidal activities with matrine, hexaflumuron and rotenone against Plutella xylostella. In current study, plumbagin and juglone were discovered as parent structures, which lays a foundation for their application in plant protection.

The Vertical Contour Calcanectomy, an Alternative Approach to Surgical Heel Ulcers: A Case Series.

Heel ulcers have a significant impact on lower-extremity morbidity and confer high risk of major amputations. Treating these ulcers is difficult because of poor tissue coverage and the bony os calcis, often leading to proximal amputation. This case series shows the vertical contour calcanectomy (VCC) as a surgical alternative in functional limb salvage. Sixteen feet (14 patients) with recalcitrant heel wounds who underwent VCC were identified. The minimum follow-up time for inclusion was 1 year. Body mass index, diabetes, renal disease, peripheral vascular disease, lymphedema/venous insufficiency, smoking status, Charcot, amputation, vascular intervention, wound recurrence, reoperation rate, and ambulatory status were evaluated. The average follow-up time was 27.1 months (range 13.5 to 51.1). At 1 year of follow-up, 56% of heel wounds (9 of 16) treated with the VCC remained closed. An average of 1.44 subsequent surgeries were required per patient. Baseline or improved ambulatory status was achieved in 69% of patients (9 of 14) at 1-year follow up and 100% of patients (8 of 8) at 2-year follow up. The overall rate of major amputation was 19%. The long-term ambulatory status of patients treated with the VCC shows promise. The VCC should be considered as an alternative, reliable, surgical limb salvage tool for heel ulcerations.

The Vertical Contour Calcanectomy: An Alternative Surgical Technique to the Conventional Partial Calcanectomy.

Heel ulcers have a significant impact on lower extremity morbidity and confer a high risk for major amputations. Although there are many conservative treatment options, once calcaneal osteomyelitis occurs or a heel ulcer becomes chronic or recalcitrant, more invasive management is required. The partial calcanectomy is a surgical solution that can address both pathologies-the ulceration and the infected bone. The conventional partial calcanectomy, however, does not ensure complete soft tissue closure. Often, closure under tension is required for primary closure of the soft tissue deficit or the wound must be closed by secondary intention. This process occurs, in part, when the proportion of bone resected is insufficient in relation to the size of the wound. Closure under tension increases the possibility of dehiscence and subsequent postoperative surgical site complications that lead to the same risks for major amputation as the index heel ulcer. This article introduces and describes a novel modification to the conventional partial calcanectomy and addresses these aforementioned concerns. The vertical contour calcanectomy incorporates improvements to an already accepted limb salvage technique. The purpose of this article was to describe the indications, contraindications, intraoperative technique and postoperative management of the vertical contour calcanectomy for patients who present with heel ulcers in the limb salvage setting.

Upregulated Serum MiR-146b Serves as a Biomarker for Acute Ischemic Stroke.

BACKGROUND/AIMS: Stroke is a major cerebrovascular disease threatening human health and life with high morbidity, disability and mortality. It is aimed to find effective biomarkers for the early diagnosis on stroke. METHODS: The expressions of 17 previously reported stroke-associated miRNAs were measured using quantitative RT-PCR and the expressions of plasma high-sensitivity C reactive protein (hs-CRP) and serum interleukin 6 (IL-6), the pro-inflammation markers in brain injury, were examined using enzyme-linked immunosorbent assay in 128 acute ischemic stroke (AIS) patients and control group. RESULTS: Serum miR-146b expression was significantly increased within 24 hours after stroke onset in patients compared with control group. In addition, the upregulation of serum miR-146b was strong positively correlated with plasma hs-CRP, infarct volume and National Institutes of Health Stroke Scale (NIHSS) score, and moderate positively correlated with serum IL-6 of patients. Importantly, the combination of plasma hs-CRP and serum miR-146b gained a better sensitivity/specificity for prediction of AIS (AUC from 0.782 to 0.863). CONCLUSION: Our preliminary findings suggested that upregulated serum miR-146b in acute ischemic stroke might be a potential biomarker for AIS evaluation.

Naringenin prevents ischaemic stroke damage via anti-apoptotic and anti-oxidant effects.

Apoptosis and oxidative stress are considered to be the major factors associated with the development and progression of many ischaemic cerebrovascular diseases. Naringenin (NAR) is an abundant flavanone in citrus plants and has been found to exhibit anti-oxidant, anti-carcinogenic and anti-apoptotic effects. This study aimed to investigate the anti-apoptotic and anti-oxidant effects of naringenin on ischaemic stroke. In vitro, cortical neuron cells isolated from the brains of neonatal Sprague-Dawley rats were randomly divided into control, oxygen and glucose deprivation/reperfusion (OGD/Rep), NAR-L, NAR-M and NAR-H groups. MTT and RT-PCR were used for cell proliferation and apoptosis-related proteins analyses. The effects of NAR on the Nrf2 signalling pathway were investigated using transfection approaches. Differences in mitochondrial dysfunction were analyzed by flow cytometry. In vivo, middle cerebral artery occlusion (MCAO) model was prepared and neurological defects and the brain wet/dry (W/D) ratio were assessed and recorded; apoptosis was measured based on the TUNEL assay. Additionally, biochemical indices were detected both in vitro and in vivo. NAR promoted cortical neuron cell proliferation, inhibited apoptosis and oxidative stress, and regulated the localization of Nrf2 protein (P<.05). Furthermore, silencing and overexpression of Nrf2 affected cortical neuron cell proliferation and apoptosis (P<.05). In vivo, NAR could alleviate cerebral oedema, improve neurological defects, and reduce apoptosis and oxidative stress (P<.05). These findings demonstrated that NAR could reduce apoptosis and oxidative stress and that Nrf2 signalling pathway is involved in this regulatory process. NAR has health-promoting properties because of its anti-apoptotic and anti-oxidant effects in cases of ischaemic stroke.

Design, Synthesis, and Biological Activities of Novel Coumarin Derivatives as Pesticide Candidates.

Food security is an important issue in the 21st century; preventing and controlling crop diseases and pests are the key to solve this problem. The creation of new pesticides based on natural products is an important and effective method. Herein, coumarins were selected as parent structures, and a series of their derivatives were designed, synthesized, and evaluated for their antiviral activities, fungicidal activities, and insecticidal activities. We found that coumarin derivatives exhibited good to excellent antiviral activities against tobacco mosaic virus (TMV). The antiviral activities of I-1, I-2a, I-4b, II-2c, II-2g, II-3, and II-3b are better than that of ribavirin at 500 µg/mL. Molecular docking research showed that these compounds had a strong interaction with TMV CP. These compounds also showed broad-spectrum fungicidal activities against 14 plant pathogenic fungi. The EC50 values of I-1, I-2a, I-3c, and II-2d are in the range of 1.56-8.65 µg/mL against Rhizoctonia cerealis, Physalospora piricola, Sclerotinia sclerotiorum, and Pyricularia grisea. Most of the compounds also displayed good insecticidal activities against Mythimna separata. Pesticide-likeness analysis showed that these compounds are following pesticide-likeness and have the potential to be developed as pesticide candidates. The present work lays a foundation for the discovery of novel pesticide lead compounds based on coumarin derivatives.

Carboxymethyl chitosan composited poly(ethylene oxide) electrolyte with high ion conductivity and interfacial stability for lithium metal batteries.

Low ionic conductivity and poor interface stability of poly(ethylene oxide) (PEO) restrict the practical application as polymeric electrolyte films to prepare solid-state lithium (Li) metal batteries. In this work, biomass-based carboxymethyl chitosan (CMCS) is designed and developed as organic fillers into PEO matrix to form composite electrolytes (PEO@CMCS). Carboxymethyl groups of CMCS fillers can promote the decomposition of Lithium bis(trifluoromethane sulfonimide) (LiTFSI) to generate more lithium fluoride (LiF) at CMCS/PEO interface, which not only forms ionic conductive network to promote the rapid transfer of Li+ but also effectively enhances the interface stability between polymeric electrolyte and Li metal. The enrichment of carboxyl, hydroxyl, and amidogen functional groups within CMCS fillers can form hydrogen bonds with ethylene oxide (EO) chains to improve the tensile properties of PEO-based electrolyte. In addition, the high hardness of CMCS additives can also strengthen mechanical properties of PEO-based electrolyte to resist penetration of Li dendrites. LiLi symmetric batteries can achieve stable cycle for 2500 h and lithium iron phosphate full batteries can maintain 135.5 mAh g-1 after 400 cycles. This work provides a strategy for the enhancement of ion conductivity and interface stability of PEO-based electrolyte, as well as realizes the resource utilization of biomass-based CMCS.

Characterization of flavor volatiles in raw and cooked pigmented onion (Allium cepa L) bulbs: A comparative HS-GC-IMS fingerprinting study.

Variations in volatile flavor components in pigmented onion bulbs (purple, white, and yellow) before and after cooking were characterized by headspace gas chromatography-ion migration spectrometry (HS-GC-IMS) to investigate their odor traits. Results showed that 39 and 45 volatile flavor compounds were identified from pigmented onion bulbs before and after cooking via the HS-GC-IMS fingerprinting, respectively. Sulfurs (accounting for 50.65%-63.42%), aldehydes (13.36%-22.11%), and alcohols (11.32%-17.94%) ranked the top three prevailing compound categories in all pigmented onions (both raw and cooked). Compared to the raw colored onion bulbs, the relative proportion of sulfurs in cooked onions decreased, whereas the relative proportion of alcohols, esters, pyrazines, and furans increased. Two reliable prediction models were established through orthogonal partial least squares-discriminant analysis (OPLS-DA), and 8 and 22 distinctive odor compounds were sieved out by variable importance in projection (VIP>1.0) as volatile labels, respectively. Both principal component analysis (PCA) and clustering heatmap exhibited favorable distinguishing effects for various pigmented onion bulbs before and after cooking. These results might offer insights into understanding the odor characteristics of different pigmented onions.

Bioconversion of spray corn husks into L-lactic acid with liquid hot water pretreatment.

Agricultural by-products like rice husk, bran, and spray corn husks, often utilized as feed, are considered less desirable. This study aims to enhance the utilization rate of these materials by subjecting then to liquid hot water (LHW) pretreatment, followed by enzymatic hydrolysis to produce fermentable sugars. We investigated the production of L-lactic acid using two methods: simultaneous saccharification fermentation (SSF) and separate hydrolysis fermentation (SHF), following varying intensities of LHW pretreatment. The results showed that the optimal enzymatic hydrolysis efficiency was achieved from spray corn husks under the pretreatment conditions of 155 °C and 15 min. SHF was generally more effective than SSF. The glucose L-lactic acid conversion rate in SHF using spray corn husks can reach more than 90 %. Overall, this work proposed a novel, environmental-friendly strategy for efficient and for L- lactic acid production from spray corn husks.

Functional Characterization of CYP6QE1 and CYP6FV21 in Resistance to λ-Cyhalothrin and Imidacloprid in Bradysia odoriphaga.

Cytochrome P450 monooxygenases (P450s) belong to a family of metabolic enzymes that are involved in the detoxification of insecticides. In this study, our bioassay results showed that a field-collected population of Bradysia odoriphaga displayed a moderate resistance to λ-cyhalothrin and imidacloprid. Compared to susceptible population, CYP6QE1 and CYP6FV21 were significantly overexpressed in the field population. The expression of CYP6QE1 and CYP6FV21 was more abundant in the third and fourth larval stages, and CYP6QE1 and CYP6FV21 were most highly expressed in the midgut and Malpighian tubules. Exposure to λ-cyhalothrin and imidacloprid significantly increased the expression levels of CYP6QE1 and CYP6FV21. Furthermore, the silencing of CYP6QE1 and CYP6FV21 significantly increased the susceptibility of B. odoriphaga larvae to λ-cyhalothrin and imidacloprid. The overexpression of CYP6QE1 and CYP6FV21 significantly enhanced the tolerance of transgenic Drosophila melanogaster lines to λ-cyhalothrin and imidacloprid. In addition, molecular docking revealed that these two P450 proteins have strong binding affinity toward λ-cyhalothrin and imidacloprid insecticides. Taken together, these results indicate that the overexpression of CYP6QE1 and CYP6FV21 is responsible for resistance to λ-cyhalothrin and imidacloprid in B. odoriphaga.

High-quality faba bean reference transcripts generated using PacBio and Illumina RNA-seq data.

The genome of faba bean was first published in 2023. To promote future molecular breeding studies, we improved the quality of the faba genome based on high-density genetic maps and the Illumina and Pacbio RNA-seq datasets. Two high-density genetic maps were used to conduct the scaffold ordering and orientation of faba bean, culminating in an increased length (i.e., 14.28 Mbp) of chromosomes and a decrease in the number of scaffolds by 45. In gene model mining and optimisation, the PacBio and Illumina RNA-seq datasets from 37 samples allowed for the identification and correction 121,606 transcripts, and the data facilitated a prediction of 15,640 alternative splicing events, 2,148 lncRNAs, and 1,752 fusion transcripts, thus allowing for a clearer understanding of the gene structures underlying the faba genome. Moreover, a total of 38,850 new genes including 56,188 transcripts were identified compared with the reference genome. Finally, the genetic data of the reference genome was integrated and a comprehensive and complete faba bean transcriptome sequence of 103,267 transcripts derived from 54,753 uni-genes was formed.

Is air pollution politics or economics? Evidence from industrial heterogeneity.

This paper checks the asymmetrical impact of Beijing's and Shanghai's air quality (AQ) on cross-industries stock returns (SR) by using the quantile-on-quantile (QQ) regression method. The major empirical findings as shown as followings. There are heterogeneous responses from SR to AQ within the same city. Different links are discovered for Beijing and Shanghai within the same industry. Air pollution does not have political or economic properties for all industries. Our research provides useful contributions compared with past literature. First of all, we distinguish whether air pollution is political or economic. Apart from psychology and physiology, government intervention and economic expectation are also important components in interpreting the influence from AQ to SR. Second, this study adequately considers the heterogeneity of industries. Industries differently react to the identical extrinsic shock, depending on the nature of their industry. Besides, the QQ approach captures quantile-varying relationship between variables, and does not need to consider structural fracture and time lag effects. The practical significance is that investors need to focus on national industrial policies, and avoiding biased decisions in stock market from air pollution.

What affects China's green finance? Evidence from cryptocurrency market, oil market, and economic policy uncertainty.

This paper discusses the dynamic long- and short-term effects of bitcoin price (BTP), crude oil price (COP), and uncertainty of economic policy (EPU) on China's green bond (CGB) market, separately. Depending on the quantile autoregressive distributed lag method, the empirical results are shown that BTP and EPU exert substantial positive and negative effects on the CGB market in the long term for most circumstances, while their effects reflect not prominent in the short term. The main contributions can be summarized as follows. Given that China is the largest bitcoin mining state and a major green bond issuer, this study first explores the linkages between them. Furthermore, both long- and short-term effects are investigated from BTP, COP, and EPU to CGB, and long-term effects are dominated in the interrelationships among variables, indicating that the CGB market is mainly driven by permanent shocks. In addition, the mentioned long-term effects are deeply discussed from time- and quantile-varying aspects. This approach considers diverse situations in the bond market and various incidents that occur at various durations of time. The results underscore the significance of market participants gaining a deeper comprehension of how BTP, COP, and EPU impact green bond within varying market conditions. Implementing specific policies, such as establishing a cohesive and efficient bond market and making careful adjustments to economic policies, can be advantageous in maintaining stability within the CGB market.

Reversible splenial lesion syndrome type II in youth mimicking acute ischemic stroke like onset: A case report.

BACKGROUND: Reversible splenial lesion syndrome (RESLES) is a newly recognized syndrome. Its typical pathologic findings is a reversible progress correlated with transiently reduced diffusion lesion in the splenium of the corpus callosum. The common clinical symptoms include mildly altered states consciousness, delirium, and seizure. METHODS: We presented a 21-year-old patient with signs of acute ischemic stroke (AIS), including symptoms of weakness on the right upper limb and aphasia, lasting 50 minutes until he was taken to the emergency. He just had a cough 20 days ago. RESULTS: An elevated level of white blood cell count, neutrophil count, monocyte count, protein of cerebrospinal fluid was found in laboratory examinations. Magnetic resonance imaging revealed distinct lesions involving white matter in the splenium of the corpus callosum and frontal-parietal cortex on both cerebral hemispheres. Digital subtraction angiography examination was also unremarkable. The patient recovered to baseline within 4 days. We treated the patient with glucocorticoid, antiviral drugs, butylphthalide, and dehydrating drugs. In addition, the follow-up brain magnetic resonance imaging scan showed reduced lesions. AIS-like symptoms did not occur during a 30-day follow-up period. CONCLUSION: This patient with reversible splenial lesion syndrome type II exhibited AIS-like symptoms, which was uncommon on clinical. This case extends the recognized clinical phenotypes for this disorder.

Construction of a high-density genetic map for faba bean (Vicia faba L.) and quantitative trait loci mapping of seed-related traits.

Faba bean (Vicia faba L.) is a valuable legume crop and data on its seed-related traits is required for yield and quality improvements. However, basic research on faba bean is lagging compared to that of other major crops. In this study, an F2 faba bean population, including 121 plants derived from the cross WY7×TCX7, was genotyped using the Faba_bean_130 K targeted next-generation sequencing genotyping platform. The data were used to construct the first ultra-dense faba bean genetic map consisting of 12,023 single nucleotide polymorphisms markers covering 1,182.65 cM with an average distance of 0.098 cM. The map consisted of 6 linkage groups, which is consistent with the 6 faba bean chromosome pairs. A total of 65 quantitative trait loci (QTL) for seed-related traits were identified (3 for 100-seed weight, 28 for seed shape, 12 for seed coat color, and 22 for nutritional quality). Furthermore, 333 candidate genes that are likely to participate in the regulation of seed-related traits were also identified. Our research findings can provide a basis for future faba bean marker-assisted breeding and be helpful to further modify and improve the reference genome.

Hydrogen-Bonded Organic Framework-Polyoxometalate-Based System for Electrochromic Devices.

A porous hydrogen-bonded organic framework (HOF) structure was explored for the first time in the design of high-performance electrochromic devices (ECDs) using polyoxometalate (POM)-based charge-balancing layers as counter electrodes (CEs). The novelty of this work lies in the facile construction of films using small molecule-based EC materials to form a porous HOF structure. A full-cell model of an ECD was constructed by utilizing a POM-based CE to optimize the voltage distribution on the HOF-coated working electrode (WE). The addition of PW12O403- (PW12) on CE significantly enhanced the voltage distribution on EC electrodes and decreased the overvoltage on the WE, further preventing the formation of non-EC species and resulting in a 3.3-fold increase in the lifetime of the ECD. The optical contrast was enhanced from 47% (TiO2 only) to 68%, and the coloration efficiency was enhanced from 185 (TiO2 only) to 373 cm2 C-1. The optimized voltage distribution on the WE, leading to the fast response time and high optical EC contrast, could be explained by the charge-balancing effect. Overall, this new finding provides a robust framework for designing high-performance ECDs, taking advantage of the porous morphology and potential matching of the HOF and PW12.

Factors affecting the transmission of dengue fever in Haikou city in 2019.

In this study, due to multiple cases of dengue fever in two locations in Haikou, Hainan, several factors affecting the transmission of dengue fever in Haikou in 2019 were analyzed. It was found that dengue fever spread from two sites: a construction site, which was an epidemic site in Haikou, and the university, where only four confirmed cases were reported. Comparative analysis revealed that the important factors affecting the spread of dengue fever in Haikou were environmental hygiene status, knowledge popularization of dengue fever, educational background, medical insurance coverage and free treatment policy knowledge and active response by the government.

CUL4B-DDB1-COP1-mediated UTX downregulation promotes colorectal cancer progression.

BACKGROUND: UTX (encoded by KDM6A), a histone demethylase for H3K27me2/3, is frequently mutated in human cancers. However, its functional and regulatory mechanisms in colorectal cancer (CRC) remain unclear. METHODS: Immunohistochemistry staining was used to investigate the clinical relevance of UTX in CRC. Additionally, we generated a spontaneous mouse CRC model with conditional Utx knockout to explore the role of UTX in the colorectal tumorigenesis. Post-translational regulation of UTX was determined by co-immunoprecipitation and immunoblot analyses. RESULTS: Herein, we identify that downregulation of UTX, mediated by the Cullin 4B-DNA Damage Binding Protein-1-Constitutive Photomorphogenesis Protein 1 (CUL4B-DDB1-COP1) complex, promotes CRC progression. Utx deletion in intestinal epithelial cells enhanced the susceptibility to tumorigenesis in AOM/DSS-induced spontaneous mouse CRC model. However, this effect is primarily alleviated by GSK126, an inhibitor of histone methyltransferase EZH2. Mechanistically, EMP1 and AUTS2 are identified as putative UTX target genes mediating UTX functions in limiting intestinal tumorigenesis. Notably, the CUL4B-DDB1-COP1 complex is identified as the functional E3 ligase responsible for targeting UTX for degradation in CRC cells. Thus, Cop1 deficiency in mouse intestinal tissue results in UTX accumulation and restricts tumorigenesis. Furthermore, patient cohort analysis reveals that UTX expression is negatively correlated with clinical stage, favorable disease outcomes, and COP1 expression. CONCLUSIONS: In the current study, the tumor suppressor function and regulation of UTX in CRC provide a molecular basis and the rationale to target EZH2 in UTX-deficient CRC.

Zhuang medicine Shuanglu Tongnao Compound Recipe treats stroke by affecting the intestinal flora regulated by the TLR4/NF-κB signaling pathway.

Background: The standardized treatment of ischemic stroke (IS) with Shuanglu Tongnao Compound Recipe (SLTNCR) combined with Western medicine has improved the life quality and neurological function of patients and achieved a satisfactory clinical effect. However, the underlying mechanisms of SLTNCR in the treatment of IS remain unclear. Methods: A rat model of IS was prepared using Longa's wire bolus method. SLTNCR was administered by gavage with following doses: low dose, 7.16 g·kg-1; middle dose, 14.33 g·kg-1; high dose, 28.66 g·kg-1. The expressions of toll-like receptor 4 (TLR4), tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), IL-6, nuclear factor-κB (NF-κB), etc., brain neuron damage, small intestine structure, and the structure of intestinal flora of rats in the high, medium, and low dose SLTNCR groups as well as the Injury + Clostridium butyricum and Injury + Edaravone groups were detected by 16SrRNA gene sequencing, western blot, hematoxylin-eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR). Results: SLTNCR significantly reduced the brain water content, decreased the cerebral infarct size, and improved the neurological deficits, neuronal damage, small bowel tissue damage, and expression of inflammatory factors [B-cell CLL/lymphoma 2 (Bcl-2), BCL2 associated agonist of cell death (Bad), cleaved-caspase-3] in brain tissue. SLTNCR administration significantly inhibited expressions of TLR4, NF-κB, and inhibitor of nuclear factor kappa B (IκB), and decreased phosphorylation levels of NF-κB and IκB in the small intestinal tissues of IS rats. Moreover, SLTNCR also significantly upregulated the expression of intestinal barrier function-related molecules [zona occludens 1 (ZO-1), occludin, claudin-5] and regulated the expression of colonic TLR4, TNF-α, IL-6, and IL-1ß. SLTNCR can improve the symptoms of IS rats by improving brain and small intestinal function, particularly by regulating the TLR4/NF-κB signaling pathway, apoptotic proteins, and inflammatory factors in brain tissue. Gut microbiota analysis helped to identify the pharmacological mechanisms underlying the effects of SLTNCR on intestinal bacterial diversity and flora structure in IS rats. Conclusions: SLTNCR can alleviate symptoms of IS and the potential mechanism of its effect is to protect brain tissue by suppressing inflammation. SLTNCR can also alter the structure and diversity of the bacterial community in IS.

Identification of XAF1 as an endogenous AKT inhibitor.

AKT kinase is a key regulator in cell metabolism and survival, and its activation is strictly modulated. Herein, we identify XAF1 (XIAP-associated factor) as a direct interacting protein of AKT1, which strongly binds the N-terminal region of AKT1 to block its K63-linked poly-ubiquitination and subsequent activation. Consistently, Xaf1 knockout causes AKT activation in mouse muscle and fat tissues and reduces body weight gain and insulin resistance induced by high-fat diet. Pathologically, XAF1 expression is low and anti-correlated with the phosphorylated p-T308-AKT signal in prostate cancer samples, and Xaf1 knockout stimulates the p-T308-AKT signal to accelerate spontaneous prostate tumorigenesis in mice with Pten heterozygous loss. And ectopic expression of wild-type XAF1, but not the cancer-derived P277L mutant, inhibits orthotopic tumorigenesis. We further identify Forkhead box O 1 (FOXO1) as a transcriptional regulator of XAF1, thus forming a negative feedback loop between AKT1 and XAF1. These results reveal an important intrinsic regulatory mechanism of AKT signaling.