Mechanism of dexmedetomidine protection against cisplatin induced acute kidney injury in rats.

OBJECTIVE: This study explored the molecular mechanisms by which dexmedetomidine (Dex) alleviates cisplatin (CP)-induced acute kidney injury (AKI) in rats. METHODS: CP-induced AKI models were established, and Dex was intraperitoneally injected at different concentrations into rats in the model groups. Subsequently, rats were assigned to the control, CP, CP + Dex 10 µg/kg, and CP + Dex 25 µg/kg groups. After weighing the kidneys of the rats, the kidney arterial resistive index was calculated, and CP-induced AKI was evaluated. In addition, four serum biochemical indices were measured: histopathological damage in rat kidneys was detected; levels of inflammatory factors, interleukin (IL)-1ß, IL-18, IL-6, and tumor necrosis factor alpha, in kidney tissue homogenate of rats were assessed through enzyme-linked immunosorbent assay (ELISA); and levels of NLRP-3, caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N in kidney tissues of rats were determined via western blotting. RESULTS: Dex treatment reduced nephromegaly and serum clinical marker upregulation caused by CP-induced AKI. In addition, hematoxylin and eosin staining revealed that Dex treatment relieved CP-induced kidney tissue injury in AKI rats. ELISA analyses demonstrated that Dex treatment reduced the upregulated levels of proinflammatory cytokines in the kidney tissue of AKI rats induced by CP, thereby alleviating kidney tissue injury. Western blotting indicated that Dex alleviated CP-induced AKI by inhibiting pyroptosis mediated by NLRP-3 and caspase-1. CONCLUSION: Dex protected rats from CP-induced AKI, and the mechanism may be related to NLRP-3/Caspase-1-mediated pyroptosis.

[Effect of Zuogui Jiangtang Jieyu Formula on intestinal flora and short-chain fatty acid metabolism in rats with diabetes mellitus complicated with depression].

This study aimed to investigate the regulatory effects of Zuogui Jiangtang Jieyu Formula(ZJJ) on the intestinal flora, short chain fatty acids(SCFAs), and neuroinflammation in rats with diabetes mellitus complicated depression(DD). The DD model was established in rats and model rats were randomly divided into a model group, a positive drug(metformin + fluoxetine) group, a ZJJ low-dose group, and a ZJJ high-dose group, with eight rats in each group. Another eight rats were assigned to the blank group. Subsequently, depressive-like behavior test was conducted on the rats, and cerebrospinal fluid samples were collected to measure pro-inflammatory cytokines [interleukin-1ß(IL-1ß), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α)]. Blood serum samples were collected to measure proteins related to the hypothalamic-pituitary-adrenal axis(HPA axis), including corticotropin-releasing hormone(CRH), adrenocorticotropic hormone(ACTH), and cortisol(CORT), as well as glucose metabolism. Gut contents were collected from each group for 16S rRNA sequencing analysis of intestinal flora and SCFAs sequencing. The results indicated that ZJJ not only improved glucose metabolism in DD rats(P<0.01) but also alleviated depressive-like behavior(P<0.05) and HPA axis hyperactivity(P<0.05 or P<0.01). Besides, it also improved the neuroinflammatory response in the brain, as evidenced by a significant reduction in pro-inflammatory cytokines in cerebrospinal fluid(P<0.05 or P<0.01). Additionally, ZJJ improved the intestinal flora, causing the intestinal flora in DD rats to resemble that of the blank group, characterized by an increased Firmicutes abundance. ZJJ significantly increased the levels of SCFAs(acetic acid, butyric acid, valeric acid, and isovaleric acid)(P<0.01). Therefore, it is deduced that ZJJ can effectively ameliorate intestinal flora dysbiosis, regulate SCFAs, and thereby improve both glucose metabolism disturbances and depressive-like behavior in DD.

Effect of inappropriate admissions on hospitalization performance in county hospitals: a cross-sectional study in rural China.

BACKGROUND: Inappropriate admissions cause excessive utilization of health services compared with outpatient services. However, it is still unclear whether inappropriate admissions cause excessive use of health services compared with appropriate admissions. This study aims to clarify the differences in the hospitalization performances between appropriately admitted inpatients and inappropriately admitted inpatients. METHODS: A total of 2575 medical records were obtained after cluster sampling in three counties. Admission appropriateness was assessed by appropriateness evaluation protocol (AEP). The propensity score matching (PSM) was computed to match patients in treatment and control group with similar characteristics, and to examine the differences in the utilization of hospitalization services between the two groups. The samples were matched in two major steps in this study. In the first step, total samples were matched to examine the differences in the utilization of hospital services between the two groups using 15 individual covariates. In the second step, PSM was computed to analyze the differences between the two groups in different disease systems using 14 individual covariates. RESULTS: For the whole sample, the inappropriate group has lower expenditure of hospitalization (EOH) (difference = - 0.12, p = 0.003) and shorter length of stay (LOS) (difference = - 0.73, p = 0.016) than the appropriate group. For number of clinical inspection (NCI), it has no statistically significant difference (difference = - 0.39, p = 0.082) between the two groups. Among different disease systems, no significant differences were observed between the two groups among EOH, LOS and NCI, except that the EOH was lower in the inappropriate group than that in the appropriate group for surgical disease (difference = - 0.169, p = 0.043). CONCLUSION: Inappropriate admissions have generated excessive health service utilization compared with appropriate admissions, especially for internal diseases. The departments in charge of medical services and hospital managers should pay high attention to the health service utilization of the inappropriately admitted inpatients. Relevant medical policies should be designed or optimized to increase the appropriateness in health care service delivery and precision in clinical pathway management.

Determinants of inappropriate admissions of children to county hospitals: a cross-sectional study from rural China.

BACKGROUND: The incidence of inappropriate admissions in China has become the shackle of its' service supply system. This research aims to assess the level of children's inappropriate admissions to county hospitals in rural China and identify the characteristics and determinants of children's inappropriate admissions. METHODS: A retrospective review was conducted on data of children aged 0-14 years. A total of 771 children medical records in four county hospitals was collected by stratified random sampling in Midwestern China and was evaluated through the Rural Appropriateness Evaluation Protocol. A questionnaire survey was conducted among doctors whose names were shown in medical records. Chi-square test was used to analyse the characteristics of inappropriate admissions, and a binary logistic regression model was used to examine the determinants of inappropriate admissions. RESULTS: Inappropriate admissions indicate that patients who could have been treated as outpatients received services as inpatients. The average rate for inappropriate admissions of children in county hospitals was 61.35%. The highest rate of inappropriate admissions was found among children aged 1-5 years (68.42%). Inappropriate admissions mostly occurred in children with respiratory diseases (72.45%), circulatory diseases (72.22%) and certain infectious diseases and parasitic diseases (70.37%). Binary logistic regression analysis showed that county, normal health status, treating department, disease, the length of hospital stay and the doctor's self-evaluation on the understanding about the degree of the patient's feelings were determinants for children's inappropriate admissions. CONCLUSIONS: County hospitals have a high rate of inappropriate admissions of children. The relationship of children's inappropriate admissions to age distribution and the insurance compensation is affected by disease and hospitalisation expenses, respectively. The determinants of children's inappropriate admissions are directly related to the weak level of primary care services in the health service system, the initial requirements requested by children's admission decision makers and the interests among medical institutions and doctors.

Changes in inpatients' distribution and benefits under institution level-based quota payment for specific diseases in rural China: An interrupted time-series analysis.

The distribution of patients is increasingly disordered in China, which leads to the waste of medical resources, increase in inpatients' economic burden, and decrease in benefits from health insurance. Institution level-based quota payment for specific diseases represents a typical payment-system reform mode in rural China that rationalizes the distribution of rural inpatients. The aim of this study is to evaluate the effectiveness of this mode by estimating rural inpatients' distribution among hospitals at different levels, per capita cost of hospitalization, and actual compensation ratio and then to provide suggestions to advance this mode. Interrupted time-series analysis was applied to evaluate the effect of the reform mode in the study, and Weiyuan County, Gansu Province, was selected as our sample. Institution level-based quota payment for specific diseases in Weiyuan County has rationalized the distribution of rural inpatients and improved their benefit levels. Further research should be conducted to evaluate the appropriateness of medical services, the health outcomes of rural inpatients, and the sustainability and replicability of the policy.

Effectiveness evaluation of quota payment for specific diseases under global budget: a typical provider payment system reform in rural China.

BACKGROUND: Quota payment for specific diseases under global budget is one of the most typical modes of provider payment system reform in rural China. This study aimed to assess this reform mode from aspects of the total fee, structure of the fee and enrollees' benefits. METHODS: A total of 127,491 inpatient records from 2014 to 2016 were extracted from the New Rural Cooperative Medical Scheme (NRCMS) database in Weiyuan County, Gansu Province. Total fee, actual compensation ratio, out-of-pocket ratio, constituent ratio of the treatment fee, constituent ratio of the inspection and laboratory fee, and length of stay were selected as dependent variables. Both generalized additive models (GAMs) and multiple linear regression models were used to measure the change in dependent variables along with year. RESULTS: Prior to the adjustment of the compensation type, out-of-pocket ratio and length of stay decreased, while total fee, actual compensation ratio, constituent ratio of the treatment fee, and constituent ratio of the inspection and laboratory fee increased. After the compensation type was adjusted, the mean of the total fee increased rapidly in 2015 and remained stable in 2016. The mean length of stay increased in 2015 but decreased in 2016. A comparison of inpatients suffering from diseases covered by quota payments and those suffering from general diseases revealed that total fee, out-of-pocket ratio, and length of stay decreased and actual compensation ratio increased for the former, whereas the opposite was true for the latter. Constituent ratio of the treatment fee and constituent ratio of the inspection and laboratory fee increased for both samples, except for the constituent ratio of the inspection and laboratory fee of quota payment diseases in 2016, which did not change. CONCLUSIONS: Quota payment for specific diseases under global budget had obviously positive effects on cost control in Weiyuan, Gansu. Considering the limited coverage of quota payment for diseases, the long-term effect of this reform mode and its replicability awaits further evaluation.

Icariin protects rats against 5/6 nephrectomy-induced chronic kidney failure by increasing the number of renal stem cells.

BACKGROUND: Chronic kidney disease poses a serious health problem worldwide with increasing prevalence and lack of effective treatment. This study aimed to investigate the mechanism of icariin in alleviating chronic renal failure induced by 5/6 nephrectomy in rats. METHODS: The chronic renal failure model was established by a two-phased 5/6 nephrectomy procedure. The model rats were given daily doses of water or icariin for 8 weeks. The kidney morphology was checked by HE staining. The levels of blood urea nitrogen, serum creatinine, and serum uric acid were measured by colometric methods. The expression of specified genes was analyzed by quantitative real-time PCR and immunohistochemical staining. The number of renal stem/progenitor cells was analyzed by CD133 and CD24 immunohistochemical staining. RESULTS: Icariin protected against CDK-caused damages to kidney histology and improved renal function, significantly reduced levels of BUN, creatinine, and uric acid. Icariin inhibited the expression level of TGF-ß1 whereas upregulated HGF, BMP-7, WT-1, and Pax2 expression. Moreover, ccariin significantly increased the expression of CD24, CD133, Osr1, and Nanog in remnant kidney and the numbers of CD133(+)/CD24(+) renal stem/progenitor cells. CONCLUSIONS: These data demonstrated that icariin effectively alleviated 5/6 nephrectomy induced chronic renal failure through increasing renal stem/progenitor cells.

Investigation on the role of VEGF gene polymorphisms in the risk of osteosarcoma.

OBJECTIVE: The VEGF in low oxygen conditions are reported to prolong the survival of malignant cell, and thus this gene has a critical role in tumor growth and invasion as well as development of malignant tumor. We aimed to assess the association between the six common SNPs and the risk of osteosarcoma, and their association with environmental factors. METHODS: 176 subjects with osteosarcoma and 176 gender- and sex-matched healthy control individuals were enrolled into our study. The VEGF -2578C/A, -1156G/A, +1612G/A, +936C/T, -634G/C and -460T/C gene polymorphisms were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay according to manufacturer's instructions. RESULTS: By conditional logistic regression analysis, AA and CA+AA genotypes of VEGF -2578C/A were associated with significant increased risk of osteosarcoma compared with CC genotype, and the ORs(95%CI) were 2.32(1.18-4.60) and 1.68(1.07-2.64), respectively. Moreover, individuals with CC and TC+CC genotypes of VEGF-460T/C had significant increased risk of osteosarcoma compared with those carrying with the TT genotype, and ORs(95%CI) were 2.15(1.10-4.21) and 1.60(1.0-2.58), respectively. By stratified analysis, we did not find statistically significant associated between VEGF -2578C/A and -460T/C gene polymorphisms and cancer risk by stratification analysis. CONCLUSION: Our results suggested that VEGF -2578C/A and -460T/C gene polymorphisms may be association with an increased risk of osteosarcoma.

Transcription factor NF-Y is a functional regulator of the transcription of core clock gene Bmal1.

The circadian clock enables organisms to adjust to daily environmental changes and synchronize multiple molecular, biochemical, physiological, and behavioral processes accordingly. In mammalian clock work, Bmal1 is the most important core clock gene, which works with another core clock gene Clock to drive the expression of other clock genes and clock-controlled genes. However, the regulation of Bmal1 has not been fully understood. This work was aimed at identifying the positive regulator(s) of Bmal1 transcription. A series of 5' deletion reporter constructs was generated, and binding site mutations of mouse Bmal1 promoter fragments were cloned into pGL3-basic and pGL3(R2.1)-basic plasmids and transfected into NIH 3T3 cells. Luciferase activity was either measured 48 h after transfection or recorded for 4 days after serum shock. DNA affinity precipitation assay was used to detect the transcription factors binding to Bmal1 promoter. Small interfering RNA against nuclear factor Y, subunit A (NF-YA) and dominant negative NF-YA were employed to study the role of NF-Y in Bmal1 transcription regulation. Deletion and mutation analyses identified two clusters of CCAAT/GC-boxes at the proximal region of Bmal1 promoter as the activating cis-elements. Bmal1 promoter activity was up-regulated by NF-Y and/or Sp1 and repressed by dominant negative NF-YA or siRNA against NF-YA. The activation of Bmal1 promoter activity by NF-Y and Sp1 was inhibited by Rev-Erbα. DNA affinity precipitation assay showed that NF-Y and Sp1 bound to the two CCAAT/GC clusters of Bmal1 promoter. These results indicate that NF-Y is a functional activator of Bmal1 transcription and it cooperates with Sp1 and Rev-Erbα to generate the daily cycle of Bmal1 expression.

Activation of PI3K-Akt through taurine is critical for propofol to protect rat cardiomyocytes from doxorubicin-induced toxicity.

Myocardial toxicity is one of the major side effects of many chemotherapeutics. It has been shown that propofol can ameliorate the cardiotoxicity of chemotherapeutic agents. In this study, we intend to investigate the role of the PI3K-Akt-Bad signaling pathway in propofol relief of doxorubicin-induced oxidative stress and apoptosis in rat cardiomyocytes. Cultured neonatal rat cardiomyocytes were treated with vehicle, doxorubicin, propofol, or propofol plus doxorubicin in the presence or absence of the PI3K inhibitor LY294002. Cells were harvested 20 h post-exposure to doxorubicin followed by analysis of their cellular taurine content, oxidative/nitrative stresses, and cellular apoptosis. The activation of the PI3K-Akt pathway was analyzed by immunoblotting. FACS, TUNEL, and LDH assays showed that the viability of cardiomyocytes was markedly reduced by doxorubicin, but was improved by propofol. Doxorubicin treatment significantly elevated cellular reactive oxygen and nitrogen contents while lowering the levels of taurine, Akt, and phosphorylated Akt and Bad. The abovementioned doxorubicin-induced changes were reversed by propofol. The protective effects of propofol were abrogated by simultaneous treatment with LY294002. In conclusion, the PI3K-Akt-Bad pathway plays a critical role in conferring the protective effects of propofol against myocardial toxicity from doxorubicin.

Effects of large-scale land consolidation projects on ecological environment quality: A case study of a land creation project in Yan'an, China.

Large land consolidation projects modify the structures and functions of regional ecosystems through the reshaping of the territorial spatial pattern, thereby affecting the ecological environmental quality (EEQ). To investigate the effects of large-scale land consolidation projects on EEQ, this study takes the major land consolidation project of "bulldoze mountains to create land" (BMCL) in Yan'an City as a research object and evaluates the change of EEQ based on Remote Sensing Ecological Index (RSEI). The consolidated area and the control area were set up to comparatively analyze the EEQ change processes and spatial distribution characteristics of these two areas in the full life cycle of BMCL. According to the results, the mean RSEI of the consolidated area was 0.128 lower than that of the control area, and the EEQ of the consolidated area was always lower than that of the control area. BMCL had a strong negative impact on the EEQ grade of the consolidated area, especially in the early stage. However, the positive effect of BMCL on EEQ gradually emerged in the late stage of the large land consolidation project. The overall EEQ grade of the consolidated area has also improved. The results of the stepwise regression analysis indicated that the wetness component and the normalized differential vegetation index played key roles in improving the EEQ of the BMCL. Overall, the local BMCL strongly affected the EEQ of the consolidated area but would not cause the EEQ of the whole region to experience any dramatic, abrupt change in the short term. This study provided references for the evaluation and analysis of the ecological effects of land consolidation at the regional scale, offering a feasible way to evaluate the spatio-temporal change of EEQ in BMCL.

Effects of anterior sciatic nerve acupuncture on lower limb paralysis after cerebral infarction: study protocol for a randomized controlled trial.

Stroke is the main cause of disability in the middle and old age. Hemiplegia, especially lower limb paralysis, often leads to the loss of self-care ability and a series of secondary injuries. The main method to improve hemiplegic limb movement is exercise therapy, but there are still many patients with disabilities after rehabilitation treatment. As one of the non-pharmacological therapies for stroke, acupuncture has been recognized to improve motor function in patients. Here, we propose a new method, anterior sciatic nerve acupuncture, which can stimulate both the femoral nerve and the sciatic nerve. We designed this study to determine the effect of this method on lower limb motor function. Sixty participants recruited with hemiplegia after cerebral infarction will be randomly assigned to the test group or control group in a 1:1 ratio. The control group will receive Xingnao Kaiqiao acupuncture, and the test group will receive anterior sciatic nerve acupuncture on this basis. All participants will get acupuncture treatment once a day, 6 times a week for 2 weeks. The primary outcome is Fugl-Meyer Assessment of Lower Extremity and the secondary outcomes are Modified Ashworth Scale and Modified Barthel Index. Data will be collected before treatment, 1 week after treatment, and 2 weeks after treatment, and then statistical analysis will be performed. This study can preliminarily verify the effect of anterior sciatic nerve acupuncture on improving lower limb motor function in patients with cerebral infarction, which may provide an alternative approach for clinical treatment of hemiplegia.

Concentration properties of biopolymers via dead-end forward osmosis.

Extracellular polymeric substances (EPSs) in excess sludge of wastewater treatment plants are valuable biopolymers that can act as recovery materials. However, effectively concentrating EPSs consumes a significant amount of energy. This study employed novel energy-saving pressure-free dead-end forward osmosis (DEFO) technology to concentrate various biopolymers, including EPSs and model biopolymers [sodium alginate (SA), bovine serum albumin (BSA), and a mixture of both (denoted as BSA-SA)]. The feasibility of the DEFO technology was proven and the largest concentration ratios for these biopolymers were 94.8 % for EPSs, 97.1 % for SA, 97.8 % for BSA, and 98.4 % for BSA-SA solutions. An evaluation model was proposed, incorporating the FO membrane's water permeability coefficient and the concentrated substances' osmotic resistance, to describe biopolymers' concentration properties. Irrespective of biopolymer type, the water permeability coefficient decreased with increasing osmotic pressure, remained constant with increasing feed solution (FS) concentration, increased with increasing crossing velocity in the draw side, and showed little dependence on draw salt type. In the EPS DEFO concentration process, osmotic resistance was minimally impacted by osmotic pressure, FS concentration, and crossing velocity, and monovalent metal salts were proposed as draw solutes. The interaction between reverse diffusion metal cations and EPSs affected the structure of the concentrated substances on the FO membrane, thus changing the osmotic resistance in the DEFO process. These findings offer insights into the efficient concentration of biopolymers using DEFO.

Endoscopic Removal of an Embedded Fishbone in the Gastric Antrum.

This report showed the clinical manifestations of a 26-year-old patient who was admitted to our hospital with epigastric discomfort. Computed tomography (CT) showed a hyper-density linear object Esophagogastroduodenoscopy (EGD) revealed a submucosal bulge in the gastric antrum. And endoscopic ultrasonography (EUS) demonstrated a hyperechoic lesion with a posterior shadowing in the anechoic area. Based on the above results, a diagnosis of fishbone invasion into the antral submucosa was considered. Then endoscopic submucosal dissection (ESD) was performed and a 3-cm-long fishbone was extracted with the forceps. As a rare case, the imaging findings of the fishbone under the endoscopy and the computed tomography were described.

TDDFT study on the simultaneous sensing mechanism for peroxynitrite and glutathione by a bifunctional fluorescent probe.

Using time-dependent density functional theory (TDDFT) method, the response mechanism of a reported bifunctional fluorescent probe for simultaneous recognition of peroxynitrite and glutathione (Chem. Commun. 2018, 54, 11336) was theoretically studied. Calculated vertical excitation energies based on the ground-state and excited-state geometries were consistent with the corresponding experimental ultraviolet-visible and fluorescence spectra. In the ground state, electron delocalization in the probe was limited because its geometry was restrained by steric hindrance. Frontier molecular orbital analysis has shown that the probe should undergo photoinduced electron transfer (PET) from the benzothiazole moiety to the maleimide moiety after excitation. The nonplanar structure together with PET led to fluorescence quenching of the probe. The probe could be dealkylated by peroxynitrite anion. The resulting intramolecular hydrogen bond increasesd the planarity of the molecule, while also gave rise to an excited-state proton-transfer process. Moreover, the addition reaction between the probe and glutathione inhibited the PET process. These two analytes together contributed to the fluorescence enhancement of the final product. This theoretical sensing mechanism for peroxynitrite and glutathione may potentially be important for the design and enhancement of novel probes.

Contralateral needling at the foot of unaffected side combining with rehabilitation treatment for motor dysfunction of hand after ischemic stroke: study protocol for a randomized controlled pilot trial.

This pilot study is to assess the feasibility and the effect of a combination therapy of rehabilitation treatment and contralateral needling, which is manipulated at the foot of the unaffected side, for the recovery of the paretic hand post-stroke. This prospective pilot clinical trial will recruit 72 stroke patients with paretic hands and a disease course of 14 to 90 d. Patients will be randomized into two groups: the control group will receive conventional Xingnao Kaiqiao acupuncture and basic treatment for the stroke; based on the control group, the observation group will receive the contralateral needling at the foot of the unaffected side combined with the rehabilitation movement of the paretic hand. 12 sessions will be administrated for 2 weeks. The primary outcome, Fugl-Meyer Assessment, and the secondary outcomes, the handgrip strength, the range of motion, the modified Barthel index, and the Brunnstrom recovery stages, will be measured the recovery of the hand motor function during the 2 weeks' intervention. This study aims to investigate the instant effect of contralateral needling at the foot of the unaffected side combined with the rehabilitation treatment movement for patients with the paretic hand of Poststroke motor dysfunction and provide the previous evidence for the future large sample studies.

Andrographolide ameliorates hepatic steatosis by suppressing FATP2-mediated fatty acid uptake in mice with nonalcoholic fatty liver disease.

Excessive intrahepatocellular lipid accumulation or steatosis is caused by abnormal lipid metabolism and a common character of nonalcoholic fatty liver disease (NAFLD), which may progress into cirrhosis and hepatocellular cancer. Andrographolide (Andro) is the primary active ingredient extracted from Andrographis paniculata, showing a protective role against dietary steatosis with the mechanism not fully understood. In this study, we showed that administration of Andro (50, 100, and 200 mg/kg/day for 8 weeks, respectively) attenuated obesity and metabolic syndrome in high-fat diet (HFD)-fed mice with improved glucose tolerance, insulin sensitivity, and reduced hyperinsulinemia, hyperglycemia, and hyperlipidemia. HFD-fed mice presented hepatic steatosis, which was significantly prevented by Andro. In vitro, Andro decreased the intracellular lipid droplets in oleic acid-treated LO2 cells. The selected RT-PCR array revealed a robust expression suppression of the fatty acid transport proteins (FATPs) by Andro treatment. Most importantly, we found that Andro consistently reduced the expression of FATP2 in both the oleic acid-treated LO2 cells and liver tissues of HFD-fed mice. Overexpression of FATP2 abolished the lipid-lowering effect of Andro in oleic acid-treated LO2 cells. Andro treatment also reduced the fatty acid uptake in oleic acid-treated LO2 cells, which was blunted by FATP2 overexpression. Collectively, our findings reveal a novel mechanism underlying the anti-steatosis effect of Andro by suppressing FATP2-mediated fatty acid uptake, suggesting the potential therapeutic application of Andro in the treatment of NAFLD.

Dynamic physiological α-synuclein S129 phosphorylation is driven by neuronal activity.

In Parkinson's disease and other synucleinopathies, the elevation of α-synuclein phosphorylated at Serine129 (pS129) is a widely cited marker of pathology. However, the physiological role for pS129 has remained undefined. Here we use multiple approaches to show for the first time that pS129 functions as a physiological regulator of neuronal activity. Neuronal activity triggers a sustained increase of pS129 in cultured neurons (200% within 4 h). In accord, brain pS129 is elevated in environmentally enriched mice exhibiting enhanced long-term potentiation. Activity-dependent α-synuclein phosphorylation is S129-specific, reversible, confers no cytotoxicity, and accumulates at synapsin-containing presynaptic boutons. Mechanistically, our findings are consistent with a model in which neuronal stimulation enhances Plk2 kinase activity via a calcium/calcineurin pathway to counteract PP2A phosphatase activity for efficient phosphorylation of membrane-bound α-synuclein. Patch clamping of rat SNCA-/- neurons expressing exogenous wild-type or phospho-incompetent (S129A) α-synuclein suggests that pS129 fine-tunes the balance between excitatory and inhibitory neuronal currents. Consistently, our novel S129A knock-in (S129AKI) mice exhibit impaired hippocampal plasticity. The discovery of a key physiological function for pS129 has implications for understanding the role of α-synuclein in neurotransmission and adds nuance to the interpretation of pS129 as a synucleinopathy biomarker.

LRP130 protein remodels mitochondria and stimulates fatty acid oxidation.

Impaired oxidative phosphorylation (OXPHOS) is implicated in several metabolic disorders. Even though mitochondrial DNA encodes several subunits critical for OXPHOS, the metabolic consequence of activating mitochondrial transcription remains unclear. We show here that LRP130, a protein involved in Leigh syndrome, increases hepatic ß-fatty acid oxidation. Using convergent genetic and biochemical approaches, we demonstrate LRP130 complexes with the mitochondrial RNA polymerase to activate mitochondrial transcription. Activation of mitochondrial transcription is associated with increased OXPHOS activity, increased supercomplexes, and denser cristae, independent of mitochondrial biogenesis. Consistent with increased oxidative phosphorylation, ATP levels are increased in both cells and mouse liver, whereas coupled respiration is increased in cells. We propose activation of mitochondrial transcription remodels mitochondria and enhances oxidative metabolism.

Robotic and Microrobotic Tools for Dental Therapy.

Robotic and microrobotic tools such as dental operating microscopes and dental endoscopes are being used extensively in dental therapy, which have a significant impact on dental therapy and education. Herein, this paper reviews the state of the art of robotic and microrobotic tools for dental therapy. This article starts with a brief introduction of current robotic and microrobotic tools for dental therapy and then displays their applications in various dental problems; strengths and weaknesses are also surveyed. Lastly, the conclusion and outlook are discussed, referring to the emerging dental clinic problems and demands. This review is expected to provide guidelines for the therapeutic application of robotic and microrobotic tools and to promote the development of robots in dentistry.