mlsa-iai-msu-lab/ru_sci_bench_zho_cite_reranking huggingface dataset:
High heat flux thermal management through liquid metal driven with electromagnetic induction pump

In this paper, a novel liquid metal-based minichannel heat dissipation method was developed for cooling electric devices with high heat flux. A high-performance electromagnetic induction pump driven by rotating permanent magnets is designed to achieve a pressure head of 160 kPa and a flow rate of 3.24 L/min, which could enable the liquid metal to remove the waste heat quickly. The liquid metal-based minichannel thermal management system was established and tested experimentally to investigate the pumping capacity and cooling performance. The results show that the liquid metal cooling system can dissipate heat flux up to 242 W/cm~2 with keeping the temperature rise of the heat source below 50°C. It could remarkably enhance the cooling performance by increasing the rotating speed of permanent magnets. Moreover, thermal contact resistance has a critical importance for the heat dissipation capacity. The liquid metal thermal grease is introduced to efficiently reduce the thermal contact resistance (a decrease of about 7.77×10~(-3)℃/W). This paper provides a powerful cooling strategy for thermal management of electric devices with large heat power and high heat flux.
Ultrasound-guided prostate percutaneous intervention robot system and calibration by informative particle swarm optimization

Applying a robot system in ultrasound-guided percutaneous intervention is an effective approach for prostate cancer diagnosis and treatment. The limited space for robot manipulation restricts structure volume and motion. In this paper, an 8-degree-of-freedom robot system is proposed for ultrasound probe manipulation, needle positioning, and needle insertion. A novel parallel structure is employed in the robot system for space saving, structural rigidity, and collision avoidance. The particle swarm optimization method based on informative value is proposed for kinematic parameter identification to calibrate the parallel structure accurately. The method identifies parameters in the modified kinematic model stepwise according to parameter discernibility. Verification experiments prove that the robot system can realize motions needed in targeting. By applying the calibration method, a reasonable, reliable forward kinematic model is built, and the average errors can be limited to 0.963 and 1.846 mm for insertion point and target point, respectively.
Cerebrospinal fluid and blood biomarkers in the diagnostic assays of Alzheimer's disease

The anti-amyloid-β(anti-Aβ)fibrils and soluble oligomers antibody aducanumab were approved to effectively slow down the progression of Alzheimer's disease(AD)at higher doses in 2019, reaffirming the therapeutic effects of targeting the core pathology of AD. A timely and accurate diagnosis in the prodromal or pre-dementia stage of AD is essential for patient recruitment, stratification, and monitoring of treatment effects. AD core biomarkers amyloid-β(Aβ_(1-42)), total tau(t-tau), and phosphorylated tau(p-tau)have been clinically validated to reflect AD-type pathological changes through cerebrospinal fluid(CSF)measurement or positron-emission tomography(PET)and found to have high diagnostic performance for AD identification in the stage of mild cognitive impairment. The development of ultrasensitive immunoassay technology enables AD pathological proteins such as tau and neurofilament light(NFL)to be measured in blood samples. However, combined biomarker detection or targeting multiple biomarkers in immunoassays will increase detection sensitivity and specificity and improve diagnostic accuracy. This review summarizes and analyzes the performance of current detection methods for early diagnosis of AD, and provides a concept of detection method based on multiple biomarkers instead of a single target, which may become a potential tool for early diagnosis of AD in the future.
FAM134B-mediated ER-phagy regulates ER-mitochondria interaction through MAMs

Endoplasmic reticulum(ER)is the largest organelle in eukaryotic cells, which can participate in the maintenance of calcium(Ca~(2+))homeostasis, protein synthesis and organelle communication[1]. Endoplasmic reticulum autophagy(ER-phagy)is a cellular quality control pathway mediated by autophagy receptors. ER-phagy involves the engulfing of excess or misfolded proteins and superfluous ER membrane to form autophagosomes which are degraded by lysosome[1]. ER-phagy occurs under normal conditions and is enhanced during starvation. At present, the receptors of ER-phagy in mammalian cells include family sequence similarity 134[1], membrane B(FAM134B), SEC62, reticulin 3(RTN3), cell cycle progression 1(CCPG1), atlastin GTPase 3(ATL3), testis expressed gene 264(TEX264), tripartite motif containing 13(TRIM13, also known as RFP2), and coiled-coil domain protein 1(CALCOCO1)[2]. FAM134B is recognized as the most characteristic receptor for ER-phagy in mammalian cells[1]. FAM134B consists of a reticulonhomology domain(RHD), a C-terminal cytoplasmic domain and an N-terminal cytoplasmic domain[1]. The RHD region of FAM134B senses and induces ER membrane curvature for ER-phagy. The LC3-interacting region(LIR), located in the C-terminal cytoplasmic domain of FAM134B, is responsible for recruiting and binding the autophagy modifiers LC3 and GABARAP, which involves the engulfing of degradable cargo to phagophore membranes for ER-phagy[1,3]. FAM134B plays a critical role in ER function and quality control through mediating ER-phagy. Inhibition of FAM134B expression leads to ER expansion. Contrarily, up-regulation of FAM134B level results in ER fragmentation[1].
LncRNA-6395 promotes myocardial ischemia-reperfusion injury in mice through increasing p53 pathway

Myocardial ischemia-reperfusion (I/R) injury is a pathological process characterized by cardiomyocyte apoptosis,which leads to cardiac dysfunction.Increasing evidence shows that abnormal expression of long noncoding RNAs (IncRNAs) plays a crucial role in cardiovascular diseases.In this study we investigated the role of IncRNAs in myocardial I/R injury.Myocardial I/R injury was induced in mice by ligating left anterior descending coronary artery for 45 min followed by reperfusion for 24 h.We showed that IncRNA KnowTID_00006395,termed IncRNA-6395 was significantly upregulated in the infarct area of mouse hearts following I/R injury as well as in H_2O_2-treated neonatal mouse ventricular cardiomyocytes (NMVCs).Overexpression of IncRNA-6395 led to cell apoptosis and the expression change of apoptosis-related proteins in NMVCs,whereas knockdown of IncRNA-6395 attenuated H_2O_2-induced cell apoptosis.LncRNA-6395 knockout mice (IncRNA-6395~(+/-)) displayed improved cardiac function,decreased plasma LDH activity and infarct size following I/R injury.We demonstrated that IncRNA-6395 directly bound to p53,and increased the abundance of p53 protein through inhibiting ubiquitination-mediated p53 degradation and thereby facilitated p53 translocation to the nucleus.More importantly,overexpression of p53 canceled the inhibitory effects of IncRNA-6395 knockdown on cardiomyocyte apoptosis,whereas knockdown of p53 counteracted the apoptotic effects of IncRNA-6395 in cardiomyocytes.Taken together,IncRNA-6395 as an endogenous pro-apoptotic factor,regulates cardiomyocyte apoptosis and myocardial I/R injury by inhibiting degradation and promoting sub-cellular translocation of p53.
Iptakalim improves cerebral microcirculation in mice after ischemic stroke by inhibiting pericyte contraction

Pericytes are present tight around the intervals of capillaries,play an essential role in stabilizing the blood-brain barrier,regulating blood flow and immunomodulation,and persistent contraction of pericytes eventually leads to impaired blood flow and poor clinical outcomes in ischemic stroke.We previously show that iptakalim,an ATP-sensitive potassium (K-ATP) channel opener,exerts protective effects in neurons,and glia against ischemia-induced injury.In this study we investigated the impacts of iptakalim on pericytes contraction in stroke.Mice were subjected to cerebral artery occlusion (MCAO),then administered iptakalim (10 mg/kg,ip).We showed that iptakalim administration significantly promoted recovery of cerebral blood flow after cerebral ischemia and reperfusion.Furthermore,we found that iptakalim significantly inhibited pericytes contraction,decreased the number of obstructed capillaries,and improved cerebral microcirculation.Using a collagen gel contraction assay,we demonstrated that cultured pericytes subjected to oxygen-glucose deprivation (OGD) consistently contracted from 3 h till 24 h during reoxygenation,whereas iptakalim treatment (10µM) notably restrained pericyte contraction from 6 h during reoxygenation.We further showed that iptakalim treatment promoted K-ATP channel opening via suppressing SUR2/EPAC1 complex formation.Consequently,it reduced calcium influx and ET-1 release.Taken together,our results demonstrate that iptakalim,targeted K-ATP channels,can improve microvascular disturbance by inhibiting pericyte contraction after ischemic stroke.Our work reveals that iptakalim might be developed as a promising pericyte regulator for treatment of stroke.
Updates on novel pharmacotherapeutics for the treatment of nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD),characterized with hepatocellular steatosis,ballooning,lobular inflammation,fibrotic progression,and insulin resistance.NASH may progress to cirrhosis and hepatocellular carcinoma (HCC),which are the major indications for liver transplantation and the causes for mortality.Thus far,there are no approved pharmacotherapeutics for the treatment of NASH.Given the complexity of NASH pathogenesis at multifaceted aspects,such as lipotoxicity,inflammation,insulin resistance,mitochondrial dysfunction and fibrotic progression,pharmacotherapeutics under investigation target different key pathogenic pathways to gain either the resolution of steatohepatitis or regression of fibrosis,ideally both.Varieties of pharmacologic candidates have been tested in clinical trials and have generated some positive results.On the other hand,recent failure or termination of a few phase II and III trials is disappointing in this field.In face to growing challenges in pharmaceutical development,this review intends to summarize the latest data of new medications which have completed phase II or III trials,and discuss the rationale and preliminary results of several combinatory options.It is anticipated that with improved understanding of NASH pathogenesis and critical endpoints,efficient pharmacotherapeutics will be available for the treatment of NASH with an acceptable safety profile.
Inhibition of drug-metabolizing enzymes by Jingyin granules:implications of herb-drug interactions in antiviral therapy

Jingyin granules,a marketed antiviral herbal medicine,have been recommended for treating H1N1 influenza A virus infection and Coronavirus disease 2019 (COVID-19) in China.To fight viral diseases in a more efficient way,Jingyin granules are frequently coadministered in clinical settings with a variety of therapeutic agents,including antiviral drugs,anti-inflammatory drugs,and other Western medicines.However,it is unclear whether Jingyin granules modulate the pharmacokinetics of Western drugs or trigger clinically significant herb-drug interactions.This study aims to assess the inhibitory potency of the herbal extract of Jingyin granules (HEJG) against human drug-metabolizing enzymes and to clarify whether HEJG can modulate the pharmacokinetic profiles of Western drug(s) in vivo.The results clearly demonstrated that HEJG dose-dependently inhibited human CES1A,CES2A,CYPs1A,2A6,2C8,2C9,2D6,and 2E1;this herbal medicine also time- and NADPH-dependently inhibited human CYP2C19 and CYP3A.In vivo tests showed that HEJG significantly increased the plasma exposure of lopinavir (a CYP3A-substrate drug) by 2.43-fold and strongly prolonged its half-life by 1.91-fold when HEJG (3 g/kg) was co-administered with lopinavir to rats.Further investigation revealed licochalcone A,licochalcone B,licochalcone C and echinatin in Radix Glycyrrhizae,as well as quercetin and kaempferol in Folium Llicis Purpureae,to be time-dependent CYP3A inhibitors.Collectively,our findings reveal that HEJG modulates the pharmacokinetics of CYP substrate-drug(s) by inactivating CYP3A,providing key information for both clinicians and patients to use herb-drug combinations for antiviral therapy in a scientific and reasonable way.
Novel CDK9 inhibitor oroxylin A promotes wild-type P53 stability and prevents hepatocellular carcinoma progression by disrupting both MDM2 and SIRT1 signaling

Hepatocellular carcinoma (HCC) is one of the most lethal tumours worldwide.However,the effects of first-line sorafenib treatment in advanced HCC fail to prolong patients' survival due to the highly heterogeneous characteristics of HCC etiology.Cyclin-dependent kinase 9 (CDK9) is an important target in the continuous development of cancer therapy.Here,we demonstrate that CDK9 is closely associated with the progression of HCC and can serve as an HCC therapeutic target by modulating the recovery of wild-type p53 (wt-p53) function.We prove that mouse double minute 2 homologue (MDM2) and Sirtuin 1 (SIRT1) are phosphorylated by CDK9 at Ser166 and Ser47,respectively.Inhibition of CDK9 not only reduces the MDM2-mediated ubiquitination and degradation of wt-p53 but also increases wt-p53 stability by suppressing deacetylase activity of SIRT1.Thus,inhibition of CDK9 promotes the wt-p53 stabilization and prevents HCC progression.However,excessive inhibition by high concentrations of specific CDK9 inhibitors counteracts the promotion of p53 stability and reduces their anti-HCC activity because of extreme general transcription repression.The effects of a novel CDK9 inhibitor named oroxylin A (OA) from Scutellaria baicalensis are explored,with the results indicating that OA shows moderate and controlled inhibition of CDK9 activity and expression,and stabilizes wt-p53 by inhibiting CDK9-regulated MDM2 and SIRT1 signaling.These outcomes indicate the high therapeutic potential of OA against HCC and its low toxicity in normal tissue.This study demonstrates a novel mechanism for the regulation of wt-p53 by CDK9 and indicates that OA is a potential candidate for HCC therapy.
Danshensu alleviates pseudo-typed SARS-CoV-2 induced mouse acute lung inflammation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can induce acute inflammatory response like acute lung inflammation (ALI) or acute respiratory distress syndrome,leading to severe progression and mortality.Therapeutics for treatment of SARS-CoV-2-triggered respiratory inflammation are urgent to be discovered.Our previous study shows that Salvianolic acid C potently inhibits SARS-CoV-2 infection.In this study,we investigated the antiviral effects of a Salvia miltiorrhiza compound,Danshensu,in vitro and in vivo,including the mechanism of S protein-mediated virus attachment and entry into target cells.In authentic and pseudo-typed virus assays in vitro,Danshensu displayed a potent antiviral activity against SARS-CoV-2 with EC_(50) of 0.97 µM,and potently inhibited the entry of SARS-CoV-2 S protein-pseudo-typed virus (SARS-CoV-2 S) into ACE2-overexpressed HEK-293T cells (IC_(50)=0.31 µM) and Vero-E6 cell (IC_(50)=4.97 µM).Mice received SARS-CoV-2 S via trachea to induce ALI,while the VSV-G treated mice served as controls.The mice were administered Danshensu (25,50,100 mg/kg,i.v.,once) or Danshensu (25,50,100 mg·kg~(-1)·d~(-1),oral administration,for 7 days) before SARS-CoV-2 S infection.We showed that SARS-CoV-2 S infection induced severe inflammatory cell infiltration,severely damaged lung tissue structure,highly expressed levels of inflammatory cytokines,and activated TLR4 and hyperphosphorylation of the NF-κB p65;the high expression of angiotensinogen (AGT) and low expression of ACE2 at the mRNA level in the lung tissue were also observed.Both oral and intravenous pretreatment with Danshensu dose-dependently alleviated the pathological alterations in mice infected with SARS-CoV-2 S.This study not only establishes a mouse model of pseudo-typed SARS-CoV-2 (SARS-CoV-2 S) induced ALI,but also demonstrates that Danshensu is a potential treatment for COVID-19 patients to inhibit the lung inflammatory response.
Dual Diomarkers Triggered Prodrugs for Precise Treatment of Melanoma: Design,Synthesis and Activities

Targeted prodrug strategy, which utilizes the endogenous biomarkers in cancer cells as activators to release the active drug, has been well established either in the fundamental research or the clinical treatment. However, many prodrugs suffer from safety concern due to "off-target activation". Dual or multiple biomarkers triggered prodrug may provide an effective strategy to overcoming the "off-target effect". Melanoma cells have both high levels of reactive oxygen species(ROS) and tyrosinase(TYR), which makes them significantly different from other tumor cells and normal cells. Here we reported a series of quinazolinone-aryl boronic acid/ester-based prodrugs, which can be activated by the cascade of ROS and TYR and selectively kill melanoma cells. The structure-activity relationship(SAR) analysis revealed that mitochondria-targeting property was vital for their cytotoxicity and the dual activated effector played a significant role in their selectivity towards melanoma cells. Among these candidates, compound 4b showed the highest toxicity to B16, leading to an imbalance of the redox system in melanoma cells, causing mitochondrial DNA damage, and then promoting melanoma cells death.
Innovative adjuvant augments potency of a SARS-CoV-2 subunit vaccine

New adjuvants that potently improve vaccine efficacy with extremely low toxicity are urgently needed.In a recent study in Cell Research,Liu et al.show that a new STING agonist CF501 facilitates a SARS-CoV-2 subunit vaccine to elicit robust neutralizing antibody response against several subtypes of sarbecovirus and protects experimental animals from SARS-CoV-2 infection.
Quality metrics and outcomes among critically ill patients in China: results of the national clinical quality control indicators for critical care medicine survey 2015-2019

Background: It is crucial to improve the quality of care provided to ICU patient, therefore a national survey of the medical quality of intensive care units(ICUs)was conducted to analyze adherence to quality metrics and outcomes among critically ill patients in China from 2015 to 2019. Methods: This was an ICU-level study based on a 15-indicator online survey conducted in China. Considering that ICU care quality may vary between secondary and tertiary hospitals, direct standardization was adopted to compare the rates of ICU quality indicators among provinces/regions. Multivariate analysis was performed to identify potential factors for in-hospital mortality and factors related to ventilator-associated pneumonia(VAP), catheter-related bloodstream infections(CRBSIs), and catheter-associated urinary tract infections(CAUTIs). Results: From the survey, the proportions of structural indicators were 1.83% for the number of ICU inpatients relative to the total number of inpatients, 1.44% for ICU bed occupancy relative to the total inpatient bed occupancy, and 51.08% for inpatients with Acute Physiology and Chronic Health Evaluation II scores >15. The proportions of procedural indicators were 74.37% and 76.60% for 3-hour and 6-hour surviving sepsis campaign bundle compliance, respectively, 62.93% for microbiology detection, 58.24% for deep vein thrombosis prophylaxis, 1.49% for unplanned endotracheal extubations, 1.99% for extubated inpatients reintubated within 48 hours, 6.38% for unplanned transfer to the ICU, and 1.20% for 48-hour ICU readmission. The proportions of outcome indicators were 1.28‰ for VAP, 3.06‰ for CRBSI, 3.65‰ for CAUTI, and 10.19% for in-hospital mortality. Although the indicators varied greatly across provinces and regions, the treatment level of ICUs in China has been stable and improved based on various quality control indicators in the past 5 years. The overall mortality rate has dropped from 10.19% to approximately 8%. Conclusions: The quality indicators of medical care in China's ICUs are heterogeneous, which is reflected in geographic disparities and grades of hospitals. This study is of great significance for improving the homogeneity of ICUs in China.
Controlled synthesis of Pt-loaded yolk-shell TiO_2@SiO_2 nanoreactors as effective photocatalysts for hydrogen generation

Yolk-shell and hollow structures are powerful platforms for controlled release,confined nanocatalysis,and optical and electronic applications.This contribution describes a fabrication strategy for a yolk-shell nanoreactor (NR) using a post decoration approach.The widely studied yolk-shell structure of silica-coated TiO_2 (TiO_2@SiO_2) was used as a model.At first,anatase TiO_2 spheres were prepared,and subsequently were given a continuous coating of carbonaceous and silica layers.Finally,the carbonaceous layer was removed to produce a yolk-shell structure TiO_2@SiO_2.By using an in-situ photodeposition method,Pt-encased spheres (Pt-TiO_2@SiO_2) were synthesized with Pt nanoparticles grown on the surface of the TiO_2 core,which contained void spaces suitable for use as NRs.The NR showed enhanced hydrogen production with a rate of 24.56 mmol·g~(-1)·h~(-1) in the presence of a sacrificial agent under simulated sunlight.This strategy holds the potential to be extended for the synthesis of other yolk-shell photocatalytic NRs with different metal oxides.
APPLICATION OF THE FACTORIZATION METHOD TO RECOVER CUTS WITH OBLIQUE DERIVATIVE BOUNDARY CONDITION

Direct and inverse problems for the scattering of cracks with mixed oblique derivative boundary conditions from the incident plane wave are considered, which describe the scattering phenomenons such as the scattering of tidal waves by spits or reefs. The solvability of the direct scattering problem is proven by using the boundary integral equation method. In order to show the equivalent boundary integral system is Fredholm of index zero, some relationships concerning the tangential potential operator is used. Due to the mixed oblique derivative boundary conditions, we cannot employ the factorization method in a usual manner to reconstruct the cracks. An alternative technique is used in the theoretical analysis such that the far field operator can be factorized in an appropriate form and fulfills the range identity theorem. Finally, we present some numerical examples to demonstrate the feasibility and effectiveness of the factorization method.
Synthesis of Chiral Hydantoins and Thiazolidinediones via Iridium-Catalyzed Asymmetric Hydrogenation

Herein, we report an iridium-catalyzed asymmetric hydrogenation of hydantoin and thiazolidinedione derived exocyclic alkenes using our developed BiphPHOX as a ligand. The transformation shows good functional group tolerance, and gives the hydrogenated products with excellent yields (up to 99%) and enantioselectivities (up to 98% ee). A gram-scale reaction was also carried out, and provided the hydrogenated product in excellent yield with no erosion in enantioselectivity. Finally, the transformation of the hydrogenated product provided an efficient approach for the synthesis of the intermediate of a HIV protease inhibitor.
One-Pot Synthesis of Fully-Conjugated Chemically Stable Two-Dimensional Covalent Organic Framework

Covalent organic frameworks (COFs) with good chemical stability coupled with extended-conjugation structures are highly preferable. Herein, a fully-conjugated and chemically stable two-dimensional COF was synthesized by a one-pot, three-components synthesis through a successful conversion of amine, aldehyde, and alkyne groups into the quinoline units as linkages with B(C6F5)3 serving as a Lewis acid catalyst, whilst 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) was employed as an oxidant. The obtained fully conjugated 2D COF shows excellent stability in acid or base.