OTUB1 alleviates NASH through inhibition of the TRAF6-ASK1 signaling pathways.

BACKGROUND AND AIMS: NAFLD is considered as the hepatic manifestation of the metabolic syndrome, which includes insulin resistance, obesity and hyperlipidemia. NASH is a progressive stage of NAFLD with severe hepatic steatosis, hepatocyte death, inflammation, and fibrosis. Currently, no pharmacological interventions specifically tailored for NASH are approved. Ovarian tumor domain, ubiquitin aldehyde binding 1 (OTUB1), the founding member of deubiquitinases, regulates many metabolism-associated signaling pathways. However, the role of OTUB1 in NASH is unclarified. METHODS AND RESULTS: We demonstrated that mice with Otub1 deficiency exhibited aggravated high-fat diet-induced and high-fat high-cholesterol (HFHC) diet-induced hyperinsulinemia and liver steatosis. Notably, hepatocyte-specific overexpression of Otub1 markedly alleviated HFHC diet-induced hepatic steatosis, inflammatory responses, and liver fibrosis. Mechanistically, we identified apoptosis signal-regulating kinase 1 (ASK1) as a key candidate target of OTUB1 through RNA-sequencing analysis and immunoblot analysis. Through immunoprecipitation-mass spectrometry analysis, we further found that OTUB1 directly bound to tumor necrosis factor receptor-associated factor 6 (TRAF6) and suppressed its lysine 63-linked polyubiquitination, thus inhibiting the activation of ASK1 and its downstream pathway. CONCLUSIONS: OTUB1 is a key suppressor of NASH that inhibits polyubiquitinations of TRAF6 and attenuated TRAF6-mediated ASK1 activation. Targeting the OTUB1-TRAF6-ASK1 axis may be a promising therapeutic strategy for NASH.

Understanding the Excited-State Relaxation Mechanisms of Xanthophyll Lutein by Multi-configurational Electronic Structure Calculations.

The contradictory behaviors in light harvesting and non-photochemical quenching make xanthophyll lutein the most attractive functional molecule in photosynthesis. Despite several theoretical simulations on the spectral properties and excited-state dynamics, the atomic-level photophysical mechanisms need to be further studied and established, especially for an accurate description of geometric and electronic structures of conical intersections for the lowest several electronic states of lutein. In the present work, semiempirical OM2/MRCI and multi-configurational restricted active space self-consistent field methods were performed to optimize the minima and conical intersections in and between the 1Ag-, 2Ag-, 1Bu+, and 1Bu- states. Meanwhile, the relative energies were refined by MS-CASPT2(10,8)/6-31G*, which can reproduce correct electronic state properties as those in the spectroscopic experiments. Based on the above calculation results, we proposed a possible excited-state relaxation mechanism for lutein from its initially populated 1Bu+ state. Once excited to the optically bright 1Bu+ state, the system will propagate along the key reaction coordinate, i.e., the stretching vibration of the conjugated carbon chain. During this period of time, the 1Bu- state will participate in and forms a resonance state between the 1Bu- and 1Bu+ states. Later, the system will rapidly hop to the 2Ag- state via the 1Bu+/2Ag- conical intersection. Finally, the lutein molecule will survive in the 2Ag- state for a relatively long time before it internally converts to the ground state directly or via a twisted S1/S0 conical intersection. Notably, though the photophysical picture may be very different in solvents and proteins, the current theoretical study proposed a promising calculation protocol and also provided many valuable mechanistic insights for lutein and similar carotenoids.

Predictive value of red blood cell distribution width and platelet-to-lymphocyte ratio for acute kidney injury in critically ill patients.

OBJECTIVES: The purpose of this study was to explore the value of red blood cell distribution width (RDW) and platelet-to-lymphocyte ratio (PLR) in predicting the occurrence of acute kidney injury (AKI) in critically ill patients. MATERIALS AND METHODS: Among 1,500 adult patients in the intensive care unit (ICU) between January 2016 and December 2019, we examined the associations of baseline RDW and PLR with the risk of AKI development using logistical analysis. In addition, we explored the value of RDW and PLR in predicting in-hospital mortality. RESULTS: Overall, 615 (41%) patients were diagnosed with AKI. We divided the groups into two subgroups each; the high-RDW (≥ 14.045%) group had a high risk of developing AKI (OR = 5.189, 95% CI: 4.088 - 6.588), and the high-PLR (≥ 172.067) group had a risk of developing AKI too (OR = 9.11, 95% CI: 7.09 - 11.71). The areas under the receiver operating characteristic curves (AUCs) for the prediction of AKI incidence based on RDW and PLR were 0.780 (95% CI: 0.755 - 0.804) and 0.728 (95% CI: 0.702 - 0.754) (all p < 0.001), with cut-off values of 14.045 and 172.067, respectively. Moreover, a higher RDW was associated with a higher rate of hospital mortality (OR: 2.907, 2.190 - 3.858), and the risk of in-hospital mortality related to PLR was 1.534 (95% CI: 1.179 - 1.995). CONCLUSION: A higher RDW was related to a higher risk of AKI occurrence and in-hospital mortality in the ICU.

Beneficial effects of citrus leaf extract supplementation on renal vasoactive substances in rats fed with repeatedly heated palm oil diet.

Addition of citrus leaf extract (CLE) into frying oil was found to be renoprotective in rats that consumed heated palm oil diet. This study examined the effects of dietary CLE supplementation on renal vasoactive substances in rats given heated palm oil diet. Forty-two male Sprague-Dawley rats were randomly split and fed with (i) control, (ii) fresh palm oil (FPO), (iii) FPO + CLE, (iv) five-time-heated palm oil (5HPO), (v) 5HPO+CLE, (vii) ten-time-heated palm oil (10HPO) and (vii) 10HPO+CLE diets for 16 weeks. CLE was added into diet at 0.15% (w/w). CLE decreased renal angiotensin-converting enzyme, inducible nitric oxide synthase and angiotensin II expressions in rats given heated oil diets, but only decreased renal NADPH oxidase activity in the 5HPO group. Supplementation of citrus leaf extract has shown beneficial effects in regulating renal vasoactive substances in rats consumed heated palm oil diet.

Stable and Efficient Blue-Emitting CsPbBr3 Nanoplatelets with Potassium Bromide Surface Passivation.

Colloidal all-inorganic perovskites nanocrystals (NCs) have emerged as a promising material for display and lighting due to their excellent optical properties. However, blue emissive NCs usually suffer from low photoluminescence quantum yields (PLQYs) and poor stability, rendering them the bottleneck for full-color all-perovskite optoelectronic applications. Herein, a facile approach is reported to enhance the emission efficiency and stability of blue emissive perovskite nano-structures via surface passivation with potassium bromide. By adding potassium oleate and excess PbBr2 to the perovskite precursor solutions, potassium bromide-passivated (KBr-passivated) blue-emitting (≈450 nm) CsPbBr3 nanoplatelets (NPLs) is successfully synthesized with a respectably high PLQY of 87%. In sharp contrast to most reported perovskite NPLs, no shifting in emission wavelength is observed in these passivated NPLs even after prolonged exposures to intense irradiations and elevated temperature, clearly revealing their excellent photo- and thermal-stabilities. The enhancements are attributed to the formation of K-Br bonding on the surface which suppresses ion migration and formation of Br-vacancies, thus improving both the PL emission and stability of CsPbBr3 NPLs. Furthermore, all-perovskite white light-emitting diodes (WLEDs) are successfully constructed, suggesting that the proposed KBr-passivated strategy can promote the development of the perovskite family for a wider range of optoelectronic applications.

Dual Specificity Phosphatase 12 Regulates Hepatic Lipid Metabolism Through Inhibition of the Lipogenesis and Apoptosis Signal-Regulating Kinase 1 Pathways.

Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide. Due to the growing economic burden of NAFLD on public health, it has become an emergent target for clinical intervention. DUSP12 is a member of the dual specificity phosphatase (DUSP) family, which plays important roles in brown adipocyte differentiation, microbial infection, and cardiac hypertrophy. However, the role of DUSP12 in NAFLD has yet to be clarified. Here, we reveal that DUSP12 protects against hepatic steatosis and inflammation in L02 cells after palmitic acid/oleic acid treatment. We demonstrate that hepatocyte specific DUSP12-deficient mice exhibit high-fat diet (HFD)-induced and high-fat high-cholesterol diet-induced hyperinsulinemia and liver steatosis and decreased insulin sensitivity. Consistently, DUSP12 overexpression in hepatocyte could reduce HFD-induced hepatic steatosis, insulin resistance, and inflammation. At the molecular level, steatosis in the absence of DUSP12 was characterized by elevated apoptosis signal-regulating kinase 1 (ASK1), which mediates the mitogen-activated protein kinase (MAPK) pathway and hepatic metabolism. DUSP12 physically binds to ASK1, promotes its dephosphorylation, and inhibits its action on ASK1-related proteins, JUN N-terminal kinase, and p38 MAPK in order to inhibit lipogenesis under high-fat conditions. Conclusion: DUSP12 acts as a positive regulator in hepatic steatosis and offers potential therapeutic opportunities for NAFLD.

Research on the extraction method of coastal wetlands based on sentinel-2 data.

Wetlands play an important role in ecological health and sustainable development, and dynamic monitoring of their spatial distribution is crucial for developing management and conservation measures. The types of coastal wetlands are complex and diverse, natural and artificial wetlands are easily confused, making precise classification more difficult. The coastal wetland of Chongming Island in China, which has diverse types and unique and complex ecological and hydrological characteristics, was deliberately chosen as a challenging case study. The objective of this study was to research effective method of fine classification of coastal wetlands, by constructing feature variables and proposing strategies for multi-level selection and fusion of feature variables. Sentinel-2 data with rich spectral information and high spatial resolution was be used. In this study, firstly, the classification effect of characteristic variables such as vegetation index, water body index, red edge index, and texture index were evaluated. Focusing on the "different objects with same spectra" of the humid planning land and farm growing ponds, the spectral characteristics of them were analyzed and a "water-rich soil index (WRSI)" was established. Subsequently, correlation analysis and J-M distance method were used to multi-level selection for the feature variables and four sets of features combination schemes were established. Finally, random forest (RF) was applied to classify coastal wetlands using different feature combination schemes, and the accuracy of different schemes was compared and verified. The results show the following: 1)Texture features have a promoting effect on improving classification accuracy. The constructed "water rich soil index"(WRSI) has the effectively contribution to identification and classification of farm growing ponds and humid planned land, improving the overall classification accuracy by 6.52%. 2)By multi-level selecting and fusion of feature variable sets, both accuracy and efficiency for classification are improved. For different features combination schemes, the classification accuracy is up to 90.03% by integrating spectral features, spectral index, texture index, and WRSI. This study evaluates the potential of Sentinel-2 data in coastal wetland classification, constructs effective feature parameters, and provides a new idea for wetland information extraction. The resulting classification map can be used for sustainable management, ecological assessment and conservation of the coastal wetland.

Mechanistic photophysics of tellurium-substituted cytosine: Electronic structure calculations and nonadiabatic dynamics simulations.

Previously, the MS-CASPT2 method was performed to study the static and qualitative photophysics of tellurium-substituted cytosine (TeC). To get quantitative information, we used our recently developed QTMF-FSSH dynamics method to simulate the excited-state decay of TeC. The CASSCF method was adopted to reduce the calculation costs, which was confirmed to provide reliable structures and energies as those of MS-CASPT2. A detailed structural analysis showed that only 5% trajectories will hop to the lower triplet or singlet state via the twisted (S2 /S1 /T2 )T intersection, while 67% trajectories will choose the planar intersections of (S2 /S1 /T3 /T2 /T1 )P and (S2 /S1 /T2 /T1 )P but subsequently become twisted in other electronic states. By contrast, ~28% trajectories will maintain in a plane throughout dynamics. Electronic population revealed that the S2 population will ultrafast transfer to the lower triplet or singlet state. Later, the TeC system will populate in the spin-mixed electronic states composed of S1 , T1 and T2 . At the end of 300 fs, most trajectories (~74%) will decay to the ground state and only 17.4% will survive in the triplet states. Our dynamics simulation verified that tellurium substitution will enhance the intersystem crossings, but the very short triplet lifetime (ca. 125 fs) will make TeC a less effective photosensitizer.

Ovarian Tumor Domain-Containing 7B Attenuates Pathological Cardiac Hypertrophy by Inhibiting Ubiquitination and Degradation of Krüppel-Like Factor 4.

BACKGROUND: Cardiac hypertrophy (CH) is a well-established risk factor for many cardiovascular diseases and a primary cause of mortality and morbidity among older adults. Currently, no pharmacological interventions have been specifically tailored to treat CH. OTUD7B (ovarian tumor domain-containing 7B) is a member of the ovarian tumor-related protease (OTU) family that regulates many important cell signaling pathways. However, the role of OTUD7B in the development of CH is unclear. Therefore, we investigated the role of OTUD7B in CH. METHODS AND RESULTS: OTUD7B knockout mice were used to assay the role of OTUD7B in CH after transverse aortic coarctation surgery. We further assayed the specific functions of OTUD7B in isolated neonatal rat cardiomyocytes. We found that OTUD7B expression decreased in hypertrophic mice hearts and phenylephrine-stimulated neonatal rat cardiomyocytes. Furthermore, OTUD7B deficiency exacerbated transverse aortic coarctation surgery-induced myocardial hypertrophy, abnormal cardiac function, and fibrosis. In cardiac myocytes, OTUD7B knockdown promoted phenylephrine stimulation-induced myocardial hypertrophy, whereas OTUD7B overexpression had the opposite effect. An immunoprecipitation-mass spectrometry analysis showed that OTUD7B directly binds to KLF4 (Krüppel-like factor 4). Additional molecular experiments showed that OTUD7B impedes KLF4 degradation by inhibiting lysine residue at 48 site-linked ubiquitination and suppressing myocardial hypertrophy by activating the serine/threonine kinase pathway. CONCLUSIONS: These results demonstrate that the OTUD7B-KLF4 axis is a novel molecular target for CH treatment.

Melatonin Alleviates Liver Fibrosis by Inhibiting Autophagy.

OBJECTIVE: Melatonin has been reported to suppress inflammation and alleviate liver fibrosis, but its effect on autophagy in liver fibrosis has not been studied. This study investigated the effect of melatonin on autophagy in an animal model of liver fibrosis and the hepatic stellate cell (HSC)-T6 cell line. METHODS: The model was established in rats through carbon tetrachloride treatment, and melatonin was administered at three doses (2.5, 5.0, and 10.0 mg/kg). Haematoxylin and eosin staining and Van Gieson's staining were performed to examine the pathological changes of liver. The expression of alpha-smooth muscle actin (α-SMA) and Beclin1 in liver tissues was detected by immunohistochemical staining. The protein levels of α-SMA, Beclin1 and LC3 in the animal model were detected by Western blot analysis, and gene levels of Beclin1 and LC3 were detected by quantitative real-time PCR (qRT-PCR) in the animal model. HSC-T6 cells were activated by platelet-derived growth factor-BB (PDGF-BB). The expression of α-SMA, Beclin1 and collagen I was detected by Western blot analysis, and the gene expression of Beclin1 and LC3 was detected by qRT-PCR. RESULTS: Melatonin reduced the expression of α-SMA, Beclin1 and LC3 in liver tissues. In addition, melatonin inhibited the activation of HSC-T6 cells and the expression of α-SMA, Beclin1 and LC3 in these cells. These results revealed that melatonin could inhibit autophagy and HSC activation. CONCLUSION: Melatonin might ameliorate liver fibrosis by regulating autophagy, suggesting that melatonin is a potential therapeutic agent for liver fibrosis.

[Canopy interception and water harvesting function of shrubs in urban green spaces of semi-humid region and their influencing factors]. / åŠæ¹¿æ¶¦åœ°åŒºåŸŽå¸‚ç»¿åœ°çŒæœ¨çš„æˆªç•™é›†æ°´åŠŸèƒ½åŠå ¶å½±å“å› ç´ .

In the semi-humid region, developing innovative water conservation urban green space design and facilitating urban greening projects from high water consumption to water conservation are hot topics in research and practice. Using the simulated rainfall method, we explored the water interception and collection functions and their influencing factors of six shrub species (Ligustrum ×vicaryi, Euonymus japonicas, Buxus sinica var. parvifolia, Photinia ×fraseri, Juniperus chinensis and Platycladus orientalis) in urban green space in the semi-humid region. The results showed that canopy interception and water harvesting were two stages in hydrological processes. The canopy interception of coniferous shrubs was high, while their stemflow was low. When the rainfall intensity increased, throughfall rates and stem-flow rates of all shrub species increased significantly, while the interception rate relatively decreased. The throughfall and stem-flow rates of broad-leaved shrubs were significantly higher than those of coniferous shrubs. The canopy interception was significantly lower in broad-leaved shrub species than in coniferous ones. At the center of canopy projection, the throughfall rate was the lowest. The leaf area index (LAI) and throughfall rate decreased gradually from the center of the canopy projection area. When the rainfall intensity was small, the throughfall rate at the center of canopy projection area was low, and thus the interception rate and the stem-flow rate were higher. When the rainfall intensity was more elevated, throughfall at the center of canopy projection area was large, and thus the interception rate and the stem-flow rate were low. With increasing rainfall intensity, the funnel-shaped water collection system tended to shrink due to the increases of throughfall rate at the edge of canopy. Rainfall intensity and LAI were the most critical factors affecting water harvesting function. Planting broad-leaved shrubs under the forest may be more effective in water harvesting than planting coniferous shrubs.

Water-soluble AIE-active fluorescent organic nanoparticles for ratiometric detection of SO2 in the mitochondria of living cells.

We report a water-soluble AIEgen (TYDL) to be self-assembled into fluorescent organic nanoparticles (TYDLs) for specific sensing of SO2 in living hepatoma cells. It is demonstrated that the TYDLs were suitable for ratiometrically detecting endogenous and exogenous SO2 in mitochondria with good selectivity, low detection limit (75 nM) and excellent photostability (>30 min). These findings imply the great potential applications of TYDLs for the diagnosis of SO2-related diseases in cell biology.

Observation and Suppression of Stacking Interface States in Sandwich-Structured Quantum Dot Light-Emitting Diodes.

Interfacial quality of functional layers plays an important role in the carrier transport of sandwich-structured devices. Although the suppression of interface states is crucial to the overall device performance, our understanding on their formation and annihilation mechanism via direct characterization is still quite limited. Here, we present a thorough study on the interface states present in the electron transport layer (ETL) of blue quantum dot (QD) light-emitting diodes (QLEDs). A ZnO/ZnMgO bilayer ETL is adopted to enhance the electron injection into blue QDs. By probing the ETL band structure with photoelectron spectroscopy, we discover that substantial band bending exists at the ZnO/ZnMgO interface, elucidating the presence of a high density of interface states which hinder electron transport. By inserting a ZnO@ZMO interlayer composed of mixed ZnO and ZnMgO nanoparticles, the band bending and thus the interface states are observed to reduce significantly. We attribute this to the hybrid surface properties of ZnO@ZMO, which can annihilate the surface states of both the ZnO and ZnMgO layers. The introduction of a bridging layer has led to ∼40% enhancement in the power efficiency of blue QLEDs and noticeable performance boosts in green and red QLEDs. The findings here demonstrate a direct observation of interface states via detailed band structure studies and outline a potential pathway for eliminating these states for better performances in sandwich-structured devices.

Myotubularin-related protein 14 suppresses cardiac hypertrophy by inhibiting Akt.

Cardiac hypertrophy (CH) is an independent risk factor for many cardiovascular diseases, and is one of the primary causes of morbidity and mortality in elderly people. Pathological CH involves excessive protein synthesis, increased cardiomyocyte size, and ultimately the development of heart failure. Myotubularin-related protein 14 (MTMR14) is a member of the myotubularin (MTM)-related protein family, which is involved in apoptosis, aging, inflammation, and autophagy. However, its exact function in CH is still unclear. Herein, we investigated the roles of MTMR14 in CH. We show that MTMR14 expression was increased in hypertrophic mouse hearts. Mice deficient in heart MTMR14 exhibited an aggravated aortic-banding (AB)-induced CH phenotype. In contrast, MTMR14 overexpression prevented pressure overload-induced hypertrophy. At the molecular level, prevention of CH in the absence of MTMR14 involved elevations in Akt pathway components, which are key elements that regulate apoptosis and cell proliferation. These results demonstrate that MTMR14 is a new molecular target for the treatment of CH.

Deubiquitinase Ubiquitin-Specific Protease 10 Deficiency Regulates Sirt6 signaling and Exacerbates Cardiac Hypertrophy.

Background Cardiac hypertrophy (CH) is a physiological response that compensates for blood pressure overload. Under pathological conditions, hypertrophy can progress to heart failure as a consequence of the disorganized growth of cardiomyocytes and cardiac tissue. USP10 (ubiquitin-specific protease 10) is a member of the ubiquitin-specific protease family of cysteine proteases, which are involved in viral infection, oxidative stress, lipid drop formation, and heat shock. However, the role of USP10 in CH remains largely unclear. Here, we investigated the roles of USP10 in CH. Methods and Results Cardiac-specific USP10 knockout (USP10-CKO) mice and USP10-transgenic (USP10-TG) mice were used to examined the role of USP10 in CH following aortic banding. The specific functions of USP10 were further examined in isolated cardiomyocytes. USP10 expression was increased in murine hypertrophic hearts following aortic banding and in isolated cardiomyocytes in response to hypertrophic agonist. Mice deficient in USP10 in the heart exhibited exaggerated cardiac hypertrophy and fibrosis following pressure overload stress, which resulted in worsening of cardiac contractile function. In contrast, cardiac overexpression of USP10 protected against pressure overload-induced maladaptive CH. Mechanistically, we demonstrated that USP10 activation and interaction with Sirt6 in response to angiotensin II led to a marked increase in the ubiquitination of Sirt6 and resulted in Akt signaling downregulation and attenuation of cardiomyocyte hypertrophy. Accordingly, inactivation of USP10 reduced Sirt6 abundance and stability and diminished Sirt6-induced downstream signaling in cardiomyocytes. Conclusions USP10 functions as a Sirt6 deubiquitinase that induces cardiac myocyte hypertrophy and triggers maladaptive CH.

Study on the potential mechanism of naoshuantong capsule in treating cerebral infarction based on net-work pharmacology and molecular docking / 现代医院

Objective To explore the possible mechanism of Naoshuantong capsule in the treatment of cerebral infarction by network pharmacology and molecular docking technology.Methods The main active ingredients and targets of Naoshuantong Capsule were screened based on the TCMSP database.At the same time,the targets related to cerebral infarction were collected through GeneCards,OMIM,PharmGKB,TTD and DrugBank databases,and the intersection targets of drugs and diseases were obtained using InteractiVenn platform.Cytoscape software was used to construct the"active ingredient-disease target"network model.STRING database and Cytoscape software were used to construct protein interaction network diagrams,and core targets were screened according to the degree.GO functional analysis and KEGG pathway enrichment analysis were performed on inter-secting targets using R language.Finally,AutoDock Vina and Symol were used to molecularly dock the active components in the"active ingredient-disease target"network with protein targets.Results 23 active ingredients and 264 related potential targets of Naoshuantong Capsule were collected;2,043 targets related to cerebral infarction were also collected;149 common targets were obtained by the intersection of the two.It mainly acts on JUN,TNF,IL6,NFKBIA and so on,which mainly involve TNF signa-ling pathway,IL-17 signaling pathway,NF-kappa B signaling pathway and apoptosis pathway to play a role in the treatment of cerebral infarction.Molecular docking results showed that the active components of drugs in the network bind well to target pro-teins.Conclusion This study preliminarily revealed the potential multi-component,multi-target and multi-pathway mecha-nism of Naoshuantong Capsule for cerebral infarction by network pharmacology,molecular docking and bioinformatics analysis.

Mechanism of Fuling Guizhi Baizhu Gancao Decoction (Linggui Zhugan Decoction) against chronic heart failure based on the thought of "Four in One" with the theory of "Qi transformation in triple energizer" / 国际中医中药杂志

The "four-in-one" approach is based on the four-dimensional perspective of "property, position, tendency and syndrome", which helps to identify and analyze classical prescriptions in a multi-dimensional and three-dimensional way. The early pathogenesis of chronic heart failure (CHF) is deficiency of heart Qi and heart Yang and disorder in Qi transformation in triple energizer, while in the later stage of the disease, it progresses from deficiency to excess, with simultaneous occurrence of deficiency and excess syndromes. Fuling Guizhi Baizhu Gancao Decoction (Linggui Zhugan Decoction) plays its role in treating chronic heart failure by the four elements of "property, position, tendency and syndrome". Property—Linggui Zhugan Decoction is pungent, sweet, slight sweet and bitter in flavor, but warm in property. The sweet is able to tonify deficiency; the pungent is responsible for dispersing Yang, promoting Qi and draining water retention; the warm nourishes the spleen, raises Yang Qi and resolves phlegm; the bitter could excrete diuresis and dry dampness to guarantee the smooth operation of three energizer. Position-Linggui Zhugan Decoction acts on the heart, spleen and triple energizer. It can stimulate heart Yang, strengthen the spleen, resolve phlegm, and regulate the waterways to promote the Qi transformation in triple energizer. Tendency-The tendency of Linggui Zhugan Decoction is upward and downward in parallel, both internal and external. Warming up and promoting diuresis, raising Yang up and tonifying deficiency, it is conducive to the Yang Qi transformation in triple energizer. Syndrome-Linggui Zhugan Decoction is indicated for the syndrome of heart Yang deficiency and water-fluid retention, which begins with the upper abdomen swelling, Qi rushes against the chest. It is widely used in the treatment of water-vapor impulse heart disease. The disorder of Qi transformation in triple energizer is the main mechanism of recurrent CHF. Linggui Zhugan Decoction can not only warm the fire of Qi transformation in triple energizer, but also smooth the pathway of Qi transformation in triple energizer, which is compatible with the treatment of systemic fluid retention in chronic heart failure. Its pharmacological mechanisms include anti-inflammation, anti-platelet aggregation, regulation of cardiomyocyte cell membrane ion channels, protection against ischemia-reperfusion injury and modulation of vasodilation, etc. Deconstructing Linggui Zhugan Decoction with "four-in-one" approach and discussing its mechanism for treating CHF in combination with the theory of "Qi transformation in triple energizer", have great significance to rejuvenate the vitality of classical prescriptions and to apply them accurately and effectively.

Preliminary study on the mechanism of halofuginone inhibiting the activity of HepG2 cells / 药学学报

This study aimed to investigate halofuginone's inhibitory effect and mechanism on the activity of hepatocellular carcinoma cells. HepG2 cells were used to detect the effects of halofuginone. After treatment, cell activity, cell migration, cell cycle, and cell apoptosis were detected by CCK-8, transwell, and flow cytometry, respectively. The expression levels of growth and metabolism-related factors such as citrate synthase (CS), ketoglutarate dehydrogenase (OGDH), and isocitrate deoxygenase (IDH) were detected by real-time quantitative PCR and Western blot. Compared with the control group, the activity of HepG2 cells was significantly inhibited by halofuginone (P < 0.01), the migration rate of HepG2 cells was decreased (P < 0.01), the apoptosis of HepG2 cells was induced (P < 0.01), and the cell cycle was arrested in S phase (P < 0.01). The expression levels of tricarboxylic acid key enzymes CS, IDH3, and OGDH were up-regulated, the expression level of isocitrate dehydrogenase isoenzymes IDH1 and IDH2 were down-regulation. In conclusion, halofuginone can inhibit the proliferation and migration of HepG2 cells and promote apoptosis in a dose-dependent manner, which may be due to the promotion of the aerobic metabolism of cells.

Application of copy number variation sequencing in patients with intellectual disability/developmental delay and autistic spectrum disorder / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of copy number variation sequencing (CNV-seq) for the diagnosis of children with intellectual disability (ID), developmental delay (DD), and autistic spectrum disorder (ASD).@*METHODS@#Forty patients with ID/DD/ASD referred to Nanshan Maternity and Child Health Care Hospital from September 2018 to January 2022 were enrolled. G-banded karyotyping analysis was carried out for the patients. Genomic DNA was extracted from peripheral blood samples and subjected to CNV-Seq analysis to detect chromosome copy number variations (CNVs) in such patients. ClinVar, DECIPHER, OMIM and other database were searched for data annotation.@*RESULTS@#Among the 40 patients (including 30 males and 10 females), 16, 15 and 6 were diagnosed with ID, DD and ASD, respectively. One patient had combined symptoms of ID and DD, whilst the remaining two had combined ID and ASD. Four patients were found with abnormal karyotypes, including 47,XY,+mar, 46,XY,inv(8)(p11.2q21.2), 46,XX,del(5)(p14) and 46,XX[76]/46,X,dup(X)(p21.1q12). Chromosome polymorphism was also found in two other patients. CNV-seq analysis has detected 32 CNVs in 20 patients (50.0%, 20/40). Pathogenic CNVs were found in 10 patients (25.0%), 15 CNVs of uncertain clinical significance were found in 12 patients (30.0%), and 7 likely benign CNVs were found in 4 patients (10.0%).@*CONCLUSION@#Chromosome CNVs play an important role in the pathogenesis of ID/DD/ASD. CNV-seq can detect chromosomal abnormalities including microdeletions and microduplications, which could provide a powerful tool for revealing the genetic etiology of ID/DD/ASD patients.

Establishment and evaluation of risk prediction model for the esophageal cancer via whole transcriptome analysis / 中国胸心血管外科临床杂志

@#Objective    To establish the gene-based esophageal cancer (ESCA) risk score prediction models via whole transcriptome analysis to provide ideas and basis for improving ESCA treatment strategies and patient prognosis. Methods    RNA sequencing data of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC) and adjacent tissues were obtained from The Cancer Genome Atlas database. The edgeR method was used to screen out the differential genes between ESCA tissue and normal tissue, and the key genes affecting the survival status of ESCC and EAC patients were initially identified through univariate Cox regression analysis. The least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis were used to further screen genes and establish ESCC and EAC risk score prediction models. Results    The risk score prediction models were the independent prognostic factors for ESCA, and the risk score was significantly related to the survival status of patients. In ESCC, the risk score was related to T stage. In EAC, the risk score was related to lymph node metastasis, distant metastasis and clinical stage. The constructed nomogram based on risk score showed good predictive ability. In ESCC, the risk score was related to tumor immune cell infiltration and the expression of immune checkpoint genes. However, this feature was not obvious in EAC. Conclusion 聽 聽The ESCC and EAC risk score prediction models have shown good predictive capabilities, which provide certain inspiration and basis for optimizing the management of ESCA and improving the prognosis of patients.