Rhein alleviates advanced glycation end products (AGEs)-induced inflammatory injury of diabetic cardiomyopathy in vitro and in vivo models.

In diabetic patients, diabetic cardiomyopathy (DCM) is one of the most common causes of death. The inflammatory response is essential in the pathogenesis of DCM. Rhein, an anthraquinone compound, is extracted from the herb rhubarb, demonstrating various biological activities. However, it is unclear whether rhein has an anti-inflammatory effect in treating DCM. In our research, we investigated the anti-inflammatory properties as well as its possible mechanism. According to the findings in vitro, rhein could to exert an anti-inflammatory effect by reducing the production of NO, TNF-α, PGE2, iNOS, and COX-2 in RAW264.7 cells that had been stimulated with advanced glycosylation end products (AGEs). In addition, rhein alleviated H9C2 cells inflammation injury stimulated by AGEs/macrophage conditioned medium (CM). In vivo have depicted that continuous gavage of rhein could improve cardiac function and pathological changes. Moreover, it could inhibit the accumulation of AGEs and infiltration of inflammatory factors inside the heart of rats having DCM. Mechanism study showed rhein could suppress IKKß and IκB phosphorylation via down-regulating TRAF6 expression to inhibit NF-κB pathway in AGEs/CM-induced H9C2 cells. Moreover, the anti-inflammation effect of rhein was realized through down-regulation phosphorylation of JNK MAPK. Furthermore, we found JNK MAPK could crosstalk with NF-κB pathway by regulating IκB phosphorylation without affecting IKKß activity. And hence, the protective mechanism of rhein may involve the inhibiting of the TRAF6-NF/κB pathway, the JNK MAPK pathway, and the crosstalk between the two pathways. These results suggested that rhein may be a promising drug candidate in anti-inflammation and inflammation-related DCM therapy.

Kin Recognition in an Herbicide-Resistant Barnyardgrass (Echinochloa crus-galli L.) Biotype.

Despite increasing evidence of kin recognition in natural and crop plants, there is a lack of knowledge of kin recognition in herbicide-resistant weeds that are escalating in cropping systems. Here, we identified a penoxsulam-resistant barnyardgrass biotype with the ability for kin recognition from two biotypes of penoxsulam-susceptible barnyardgrass and normal barnyardgrass at different levels of relatedness. When grown with closely related penoxsulam-susceptible barnyardgrass, penoxsulam-resistant barnyardgrass reduced root growth and distribution, lowering belowground competition, and advanced flowering and increased seed production, enhancing reproductive effectiveness. However, such kin recognition responses were not occurred in the presence of distantly related normal barnyardgrass. Root segregation, soil activated carbon amendment, and root exudates incubation indicated chemically-mediated kin recognition among barnyardgrass biotypes. Interestingly, penoxsulam-resistant barnyardgrass significantly reduced a putative signaling (-)-loliolide production in the presence of closely related biotype but increased production when growing with distantly related biotype and more distantly related interspecific allelopathic rice cultivar. Importantly, genetically identical penoxsulam-resistant and -susceptible barnyardgrass biotypes synergistically interact to influence the action of allelopathic rice cultivar. Therefore, kin recognition in plants could also occur at the herbicide-resistant barnyardgrass biotype level, and intraspecific kin recognition may facilitate cooperation between genetically related biotypes to compete with interspecific rice, offering many potential implications and applications in paddy systems.

The competitiveness measurement of new energy vehicle industry based on grey relational analysis.

This study constructs an evaluation index system based on demand competitiveness, basic competitiveness, industrial agglomeration, industrial competition, industrial innovation, supporting industries, and government policy competitiveness. The study selected 13 provinces with good development of the new energy vehicle (NEV) industry as the sample. Based on the competitiveness evaluation index system, an empirical analysis was conducted to evaluate the development level of the NEV industry in Jiangsu with grey relational analysis and three-way decisions. The results reveal: 1) Under the absolute level of temporal and spatial characteristic attributes, the development of Jiangsu's NEV industry is in a leading position in the country, and the competitiveness level is closer to that of Shanghai and Beijing; 2) Under the incremental level, Jiangsu's incremental level ranks in the upper and middle reaches of 13 provinces, second only to Shanghai; 3) Under the volatility level, Jiangsu's industrial development fluctuates greatly, and the level of volatility lies in the middle reaches of the country. There is a big gap with Shanghai; 4) From the perspective of overall temporal and spatial characteristics, Jiangsu's overall industrial development level is in the first echelon in China, second only to Shanghai and Beijing, indicating that Jiangsu's NEV industry has a relatively good overall development level.

Penoxsulam-resistant barnyardgrass-mediated rhizosphere microbial communities affect the growth of rice.

BACKGROUND: The incidence of herbicide-resistant barnyardgrass is escalating in paddy fields, yet the interactions between resistant weeds and rice are largely unknown. The microbiota of herbicide-resistant barnyardgrass rhizosphere soil is critical for both barnyardgrass and rice fitness. RESULTS: Rice has different biomass allocation and root traits in the presence of penoxsulam-resistant versus penoxsulam-susceptible barnyardgrass or in their conditioned soil. Compared to susceptible barnyardgrass, resistant barnyardgrass led to an allelopathic increase in rice root, shoot, and whole-plant biomasses. Resistant barnyardgrass recruited distinct core and unique microbes in rhizosphere soil compared to susceptible barnyardgrass. In particular, resistant barnyardgrass assembled more Proteobacteria and Ascomycota to enhance plant stress tolerance. Furthermore, the root exudates from resistant and susceptible barnyardgrass were responsible for the assembly and establishment of the root microbial structure. Importantly, (-)-loliolide and jasmonic acid in root exudates were correlated with the core microbes in the rhizosphere soil. CONCLUSION: The interference of barnyardgrass with rice can be mediated by rhizosphere microbial communities. Biotype-specific variation in the ability to generate soil microbial communities appears to ameliorate the negative consequences for rice growth, providing an intriguing possibility for modulation of the rhizosphere microbiota to increase crop productivity and sustainability. © 2023 Society of Chemical Industry.

[Advances in traditional Chinese medicine treatment of non-alcoholic fatty liver disease via farnesoid X receptor].

Non-alcoholic fatty liver disease(NAFLD) is a chronic metabolic condition with rapidly increasing incidence, becoming a public health issue of worldwide concern. Studies have shown that farnesoid X receptor(FXR)-based modulation of downstream targets can improve liver function and metabolic status in the patients with NAFLD and may be a potential drug target for treating this di-sease. Great progress has been achieved in the development of drugs targeting FXR for the treatment of NAFLD. A number of studies have explored the traditional Chinese medicine and their active ingredients for the treatment of NAFLD via FXR considering the high safety and efficacy and mild side effects. This paper systematically describes the mechanism of traditional Chinese medicines in the treatment of NAFLD via FXR and the downstream targets, aiming to provide precise targets for the drug development and clinical treatment of NAFLD.

Screening of acetylcholinesterase inhibitory and antioxidant active compounds from Terminalia chebula fruits by spectrum-effect relationship and liquid chromatography-mass spectrometry analysis.

Screening and identification of active components from traditional Chinese medicines is rather challenging due to the diversity and complexity of chemical components. Herein, a comprehensive strategy based on a spectrum-effect relationship model and LC-MS analysis was developed to screen active components from Terminalia chebula fruits. The water extract of T. chebula fruits was subjected to macroporous resin column and then eluted successively with water and 30%, 50%, 70%, and 95% ethanol. The 30% ethanol eluate fractions of eighteen batches from T. chebula fruits were used for the spectrum-effect relationship study. The IC50 values for acetylcholinesterase inhibitory and 2,2-diphenyl-1-picrylhydrazyl scavenging activities were measured, LC fingerprints were established, and 15 common peaks were specified. The spectrum-effect relationship between common peaks and IC50 values was investigated by principal component analysis, gray relational analysis, partial least square and multiple linear regression. The 30% ethanol eluate fraction was further characterized by LC-MS analysis. The chromatographic peaks (Peaks 1, 2, 3, 5, 12, 14, 15) making great contributions to the efficacy were screened through a spectrum-effect relationship model, and sixteen components were further identified. The results suggested that the proposed strategy is simple and effective for acquiring active components from a complex matrix.

Associations between environmental exposure to polybrominated diphenyl ethers and nodular goiter risk: A case-control study.

Polybrominated diphenyl ethers (PBDEs) are widespread and persistent environmental contaminants, but their association with nodular goiter (NG) remains unknown. The present case-control study of 179 NG cases and 358 matched normal controls aimed to investigate the association between PBDEs and risk of NG. The plasma concentrations of 8 PBDEs congeners (BDE-28, -47, -99, -100, -153, -154, -183, and -209) were determined by gas chromatograph-mass spectrometer. Conditional logistic regression model was used to evaluate the odds ratio (OR) and 95% confidence interval (CI) for the association between each PBDEs congener and NG. Bayesian kernel machine regression (BKMR) was used to evaluate the association between overall levels of 8 PBDEs mixture and NG. The results of logistic model suggested that increased risk of NG was associated with elevated concentrations of all PBDEs congeners, except for BDE-209. In BKMR model, the risk of NG increased with the increase in overall exposure level of 8 PBDEs mixture. Compared to when all PBDEs mixture were at their median value, the risk of exposure-response function for NG increased by 0.34 units when all PBDEs were at their 75th percentile. In women, the results showed similar trends after additional adjustment for age at menarche and menopausal status. These findings provide novel epidemiological evidence for the prevention of NG. However, larger prospective studies are required to address the associations between PBDEs exposure and NG risk.

Enantioselective construction of spiro-tetrahydroquinoline scaffolds through asymmetric catalytic cascade reactions.

An efficient and concise strategy has been successfully developed for merging spiro-tetrahydroquinoline with spiro-benzofuranone into a single new skeleton through asymmetric catalytic cascade reactions catalyzed by quinine-derived chiral bifunctional squaramide organocatalysts. In this approach, differently substituted spiro-tetrahydroquinoline derivatives were smoothly obtained with high yields, and excellent diastereoselectivities and enantioselectivities (up to 99% yield, up to >20 : 1 dr, up to >99% ee, 40 examples) under mild reaction conditions.

Screening and identification of acetylcholinesterase inhibitors from Terminalia chebula fruits by immobilized enzyme on cellulose filter paper coupled with ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and molecular docking.

With the increasing demand of new drugs for the treatment of Alzheimer's disease (AD), screening acetylcholinesterase (AChE) inhibitors from traditional Chinese medicines (TCMs) has been proved to be an effective strategy for drug discovery. In present study, a novel strategy was developed to fish out AChE inhibitors from Terminalia chebula fruits based on immobilized AChE coupled with ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and molecular docking. For AChE immobilization, cellulose filter paper (CFP) as the carrier was modified with chitosan to be introduced to amino groups, and then AChE was modified on the amino-modified CFP through a Schiff base reaction with glutaraldehyde as a cross-linking agent. The CPF-immobilized AChE possessed advantages of a wider range for pH and temperature endurance, better storage stability, excellent reproducibility and reusability. The CPF-immobilized AChE was incubated with the extract of T. chebula fruits, and then the active components would form complexes with immobilized AChE. The complexes were further conveniently separated with inactive components by virtue of the instantaneous separation characteristic of CFP. Eventually, 25 (1-11, 13-26) potential AChE inhibitors were fished out and their structures were further identified by UPLC-QTOF-MS. Moreover, molecular docking was performed to discriminate non-specific compounds to AChE and explore binding mechanisms between potential inhibitors and AChE, and 25 compounds could be well embedded into active sites of AChE with affinities ranging from -9.9 to -6.4 kcal/mol. Inhibitory activities of screened active components on AChE were evaluated in vitro, and punicalagin, 1,3,6-tri-O-galloyl-ß-D-glucose (1,3,6-TGG), chebulinic acid and geraniin exhibited excellent AChE-inhibitory properties with IC50 values of 0.43 ± 0.03, 0.46 ± 0.02, 0.50 ± 0.03 and 0.51 ± 0.03 mM, respectively. The results indicated that the developed method was simple and efficient, and could be utilized to screen and identify potential AChE inhibitors from TCMs.

A Study of the Protective Effect of Bushen Huoxue Prescription on Cerebral Microvascular Endothelia Based on Proteomics and Bioinformatics.

Diabetic cognitive dysfunction is a serious complication of type 2 diabetes mellitus (T2DM), which can cause neurological and microvascular damage in the brain. At present, there is no effective treatment for this complication. Bushen Huoxue prescription (BSHX) is a newly formulated compound Chinese medicine containing 7 components. Previous research indicated that BSHX was neuroprotective against advanced glycosylation end product (AGE)-induced PC12 cell insult; however, the effect of BSHX on AGE-induced cerebral microvascular endothelia injury has not been studied. In the current research, we investigated the protective effects of BSHX on AGE-induced injury in bEnd.3 cells. Our findings revealed that BSHX could effectively protect bEnd.3 cells from apoptosis. Moreover, we analyzed the network regulation effect of BSHX on AGE-induced bEnd.3 cells injury at the proteomic level. The LC-MS/MS-based shotgun proteomics analysis showed BSHX negatively regulated multiple AGE-elicited proteins. Bioinformatics analysis revealed these differential proteins were involved in multiple processes, such as Foxo signaling pathway. Further molecular biology analysis confirmed that BSHX could downregulate the expression of FoxO1/3 protein and inhibit its nuclear transfer and inhibit the expression of downstream apoptotic protein Bim and the activation of caspase, so as to play a protective role in AGE-induced bEnd.3 injury. Taken together, these findings demonstrated the role of BSHX in the management of diabetic cerebral microangiopathy and provide some insights into the proteomics-guided pharmacological mechanism study of traditional Chinese Medicine.

Procyanidin B2 Alleviates Palmitic Acid-Induced Injury in HepG2 Cells via Endoplasmic Reticulum Stress Pathway.

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome featuring ectopic lipid accumulation in hepatocytes. NAFLD has been a severe threat to humans with a global prevalence of over 25% yet no approved drugs for the treatment to date. Previous studies showed that procyanidin B2 (PCB2), an active ingredient from herbal cinnamon, has an excellent hepatoprotective effect; however, the mechanism remains inconclusive. The present study aimed to investigate the protective effect and underlying mechanism of PCB2 on PA-induced cellular injury in human hepatoma HepG2 cells. Our results showed that PA-induced oxidative stress, calcium disequilibrium, and subsequent endoplasmic reticulum stress (ERS) mediated cellular injury, with elevated protein levels of GRP78, GRP94, CHOP, and hyperphosphorylation of PERK and IRE1α as well as the increased ratio of Bax/Bcl-2, which was restored by PCB2 in a concentration-dependent manner, proving the excellent antiapoptosis effect. In addition, 4-phenylbutyric acid (4-PBA), the ER stress inhibitor, increased cell viability and decreased protein levels of GRP78 and CHOP, which is similar to PCB2, and thapsigargin (TG), the ER stress agonist, exhibited conversely meanwhile partly counteracted the hepatic protection of PCB2. What is more, upregulated protein expression of p-IKKα/ß, p-NF-κB p65, NLRP3, cleaved caspase 1, and mature IL-1ß occurred in HepG2 cells in response to PA stress while rescued with the PCB2 intervention. In conclusion, our study demonstrated that PA induces ERS in HepG2 cells and subsequently activates downstream NLRP3 inflammasome-mediated cellular injury, while PCB2 inhibits NLRP3/caspase 1/IL-1ß pathway, inflammation, and apoptosis with the presence of ERS, thereby promoting cell survival, which may provide pharmacological evidence for clinical approaches on NAFLD.

Body mass index and weight gain after middle adulthood are associated with risk of papillary thyroid cancer: A case-control study.

BACKGROUND: It is unclear whether weight change after middle adulthood influences the risk of thyroid cancer. The aim of this study was to investigate associations between the risk of papillary thyroid cancer (PTC) and body mass index (BMI) and weight change after middle adulthood (age 35). METHODS: A matched case-control study based on three hospitals included 516 pairs of cases newly diagnosed with PTC and controls. Current height and weight after defecation in the morning were measured by trained nurses. During measurement, all subjects were requested to wear lightweight clothing and no shoes. Weight at age 35 was self-reported. BMI and weight change were modeled as continuous and categorical variables. Conditional and unconditional logistic regression models were used to estimate the odds ratio (OR) and 95% confidence interval (95%CI) for the association between BMI and weight change after middle adulthood and PTC. RESULTS: After adjustment for covariates, measured BMI at the time of current diagnosis was positively associated with PTC (OR 1.16, 95%CI 1.10-1.21). According to WHO BMI guidelines for Asia-Pacific populations, the OR (95%CI) for PTC risk in obesity was 2.99 (1.92-4.67) compared to normal weight (p-trend <0.001). Moreover, PTC was positively associated with BMI at age 35; the OR (95%CI) for PTC risk per unit increase in BMI was 1.06 (1.02-1.11). Compared to stable weight (changed <0.5 kg/year), weight gain ≥1.0 kg/year after middle adulthood was positively associated with PTC (OR 2.57, 95%CI 1.39-4.76, p-trend <0.001). Compared to maintaining non-overweight status, the PTC risk was significantly increased in those individuals who gained weight and became overweight after middle adulthood (OR 3.82, 95%CI 2.50-5.85). CONCLUSION: This study showed that high BMI and obesity were positively associated with increased risk of PTC, and weight gain after middle adulthood also could elevate the PTC risk.

Associations of exposure to multiple trace elements with the risk of goiter: A case-control study.

Goiter is one of common endocrine diseases, and its etiology has not been fully elucidated. The changes in trace elements' levels have an important impact on the thyroid. We designed a case-control study, which involved 383 goiter cases and 383 matched controls. We measured these elements in the urine of participants by inductively coupled plasma optical emission spectrometry (ICP-OES), graphite furnace atomic absorption spectrometry (GFAAS) and As3+-Ce4+ catalytic spectrophotometry. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to select the elements into multi-element models, conditional logistic regression models were applied to analyze the association between elements and goiter risk. Bayesian kernel machine regression (BKMR) model was used to depict elements' mixtures and evaluate their joint effects. Finally, 7 elements were included in the multi-element model. We found that the concentrations of lithium (Li), strontium (Sr) and barium (Ba) had a negative effect with goiter risk, and lead (Pb) and iodine (I) showed an extreme positive effect. Additionally, compared with the lowest levels, patients with highest quartiles of I and Pb were 6.49 and 1.94 times more likely to have goiter, respectively. On the contrary, in its second and third quartiles, arsenic (As) showed a negative effect (both OR<1). BKMR model showed a certain interaction among Pb, As, Sr and Li on goiter risk. Further large sample studies are needed to confirm these findings in the future.

Exposure to 2,4-dichlorophenol, 2,4,6-trichlorophenol, pentachlorophenol and risk of thyroid cancer: a case-control study in China.

Thyroid cancer (TC) has inflicted huge threats to the health of mankind. Chlorophenols (CPs) were persistent organic pollutant and can lead to adverse effects in human health, especially in thyroid. However, epidemiological studies have revealed a rare and inconsistent relationship between internal exposure to CPs and TC risk. The purpose of this study was to investigate the correlation between urinary CPs and TC risk in Chinese population. From June 2017 to September 2019, a total of 297 histologically confirmed TC cases were recruited. Age- and gender-matched controls were enrolled at the same time. Gas chromatography-mass spectrometry (GC-MS) was used to determine the levels of three CPs in urine. Conditional logistic regression models were adopted to assess the potential association. Restricted cubic spline function was used to explore the non-liner association. After adjusting for confounding factors, multivariate analysis showed that, compared with the first quartile, the fourth quartile concentrations of 2,4-dichlorophenol (2,4-DCP), 2,4,6-trichlorophenol (2,4,6-TCP), and pentachlorophenol (PCP) were associated with TC risk (odds ratio (OR)2,4-DCP =2.28, 95% confidence interval (CI): 1.24-4.18; OR2,4,6-TCP =3.09, 95% CI: 1.66-5.77; ORPCP =3.30, 95% CI: 1.71-6.36, respectively), when CPs were included in the multivariate model and restricted cubic spline function as continuous variables, presenting significant dose-response relationships. Meanwhile, whether in the TC group with tumor diameter > 1 cm or metastatic TC, the changes of 2,4,6 TCP and PCP concentrations were positively correlated with the risk of TC. Our study suggests that higher concentrations of urinary CPs are associated with increased TC risks. Moreover, 2,4,6-TCP and PCP have certain effects on the invasiveness of thyroid cancer. Targeted public health policies should be formulated to reduce the CP pollution. These findings need further in-depth studies to confirm and relevant mechanism also needed to be clarified.

Associations between essential microelements exposure and the aggressive clinicopathologic characteristics of papillary thyroid cancer.

Aim of this study was to evaluate the association between multiple essential microelements exposure and the aggressive clinicopathologic characteristics of papillary thyroid carcinoma (PTC). The concentrations of 10 essential microelements in urine [cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), strontium (Sr), zinc (Zn), and iodine (I)] were measured in 608 patients newly diagnosed with PTC, including 154 males and 454 females. Chi square test and Wilcoxon rank sum test were used to compare general characteristics among males and females. Multivariate logistic regression was used to evaluate the associations between essential microelements and PTC clinicopathologic characteristics in single- and multi-microelement models. In this study, we only observed that the frequency of lymph node metastasis in males was higher than in females, and males had higher levels of zinc than females, but males had lower levels of iodine than females. It was found that high levels of Fe were associated with decreased risk of PTC tumor size > 1 cm, capsular invasion, and advanced T stage (T3/4a/4b). High levels of Co and Mo were associated with decreased risk of capsular invasion and lymph node metastasis, respectively. However, high levels of Mn and Sr were associated with increased risk of capsular invasion and multifocality respectively, and both were associated with increased risk of advanced T stage (T3/4a/4b). These findings indicated that certain essential microelements might have potential effects on PTC progression and aggressiveness. Further studies are required to confirm these findings.

Effect of Bushen Huoxue Prescription on Cognitive Dysfunction of KK-Ay Type 2 Diabetic Mice.

Diabetic cognitive impairment is one of the common complications of type 2 diabetes, which can cause neurological and microvascular damage in the brain. Bushen Huoxue prescription (BSHX), a compound Chinese medicine, has been used clinically to treat diabetes-induced cognitive impairment. However, its underlying mechanisms remain unclear. In this study, KK-Ay diabetic model mouse was administered BSHX daily for 12 weeks. Bodyweight, random blood glucose (RBG), and fasting blood glucose (FBG) were measured every 4 weeks. Triglycerides (TG), cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting serum insulin (FINS), and Morris water maze were tested after 12 weeks of administration. On the day of sacrifice, the hippocampus was collected for pathological staining and advanced glycation end products (AGEs) analysis to evaluate the neuroprotective effect of BSHX. Our results showed that BSHX treatment significantly ameliorated the T2DM related insults, including the increased bodyweight, blood glucose, TG, insulin levels, AGEs, the reduced HDL-C, the impaired spatial memory, and the neurological impairment. Moreover, Western blot analysis showed that increased expression of receptors of AGEs (RAGEs), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and activation of nuclear factor-κB (NF-κB) in the hippocampus were significantly inhibited by BSHX treatment. These results indicate that BSHX can significantly ameliorate glucose and lipid metabolism dysfunction, reduce the morphological changes in hippocampus tissues, and improve the cognitive function of KK-Ay mice. These protective effects of BSHX may involve regulation of the AGEs/RAGE/NF-κB signaling pathway.

Critical hubs of renal ischemia-reperfusion injury: endoplasmic reticulum-mitochondria tethering complexes.

Mitochondrial injury and endoplasmic reticulum (ER) stress are considered to be the key mechanisms of renal ischemia-reperfusion (I/R) injury. Mitochondria are membrane-bound organelles that form close physical contact with a specific domain of the ER, known as mitochondrial-associated membranes. The close physical contact between them is mainly restrained by ER-mitochondria tethering complexes, which can play an important role in mitochondrial damage, ER stress, lipid homeostasis, and cell death. Several ER-mitochondria tethering complex components are involved in the process of renal I/R injury. A better understanding of the physical and functional interaction between ER and mitochondria is helpful to further clarify the mechanism of renal I/R injury and provide potential therapeutic targets. In this review, we aim to describe the structure of the tethering complex and elucidate its pivotal role in renal I/R injury by summarizing its role in many important mechanisms, such as mitophagy, mitochondrial fission, mitochondrial fusion, apoptosis and necrosis, ER stress, mitochondrial substance transport, and lipid metabolism.

Screening acetylcholinesterase inhibitors from traditional Chinese medicines by paper-immobilized enzyme combined with capillary electrophoresis analysis.

Discovering acetylcholinesterase (AChE) inhibitors is one of the important ways to develop new drugs for the treatment of Alzheimer's disease. In this work, a simple strategy was developed for screening AChE inhibitors from traditional Chinese medicines (TCMs) by capillary electrophoresis (CE) analysis combined with enzymatic assay, in which immobilized AChE was employed. For AChE immobilization, cellulose filter paper (CFP) was used as the carrier material and physically coated with chitosan owing to moderate viscosity of chitosan to be introduced into amino groups, and then AChE was covalently bonded to the amino-functionalized CFP through a Schiff base reaction using glutaraldehyde (GA) as a cross-linking agent. The CFP-immobilized AChE exhibited enhanced endurance to pH and temperature, improved storage stability, excellent repeatability and reusability. More remarkably, CFP-immobilized AChE can be instantly separated from enzyme reaction mixture thus greatly simplifying the operational process. For immobilized AChE, the Michaelis-Menten constant, inhibition constant and IC50 were determined using huperzine A as a model inhibitor. Finally, CFP-immobilized AChE was applied to inhibitor screening from 17 TCMs, among which Chebulae Fructus (ripe fruits of Terminalia chebula) exhibited the strongest inhibitory effect on AChE. The positive results indicated that such a screening strategy may open up a new avenue to discover active components from TCMs.

Machine learning in nephrology: scratching the surface.

Machine learning shows enormous potential in facilitating decision-making regarding kidney diseases. With the development of data preservation and processing, as well as the advancement of machine learning algorithms, machine learning is expected to make remarkable breakthroughs in nephrology. Machine learning models have yielded many preliminaries to moderate and several excellent achievements in the fields, including analysis of renal pathological images, diagnosis and prognosis of chronic kidney diseases and acute kidney injury, as well as management of dialysis treatments. However, it is just scratching the surface of the field; at the same time, machine learning and its applications in renal diseases are facing a number of challenges. In this review, we discuss the application status, challenges and future prospects of machine learning in nephrology to help people further understand and improve the capacity for prediction, detection, and care quality in kidney diseases.

Neuronal HMGB1 in nucleus accumbens regulates cocaine reward memory.

Cocaine is a common abused drug that can induce abnormal synaptic and immune responses in the central nervous system (CNS). High mobility group box 1 (HMGB1) is one kind of inflammatory molecules that is expressed both on neurons and immune cells. Previous studies of HMGB1 in the CNS have largely focused on immune function, and the role of HMGB1 in neurons and cocaine addiction remains unknown. Here, we show that cocaine exposure induced the translocation and release of HMGB1 in the nucleus accumbens (NAc) neurons. Gain and loss of HMGB1 in the NAc bidirectionally regulate cocaine-induced conditioned place preference. From the nucleus to the cytosol, HMGB1 binds to glutamate receptor subunits (GluA2/GluN2B) on the membrane, which regulates cocaine-induced synaptic adaptation and the formation of cocaine-related memory. These data unveil the role of HMGB1 in neurons and provide the evidence for the HMGB1 involvement in drug addiction.