Binuclear Enamino-Oxazolinate Rare-Earth Metal Complexes: Synthesis and Their Catalytic Performance in Isoprene Polymerization.

We have synthesized a series of binuclear rare-earth metal complexes bearing the newly designed enamino-oxazolinate ligands that feature bridging para-phenyl, meta-phenyl, 1,5-naphthalenyl, and 1,5-naphthalenyl moieties. NMR and X-ray diffraction analyses confirmed the binuclear structures of the obtained complexes with two enamino-oxazolinate-metal units located at a trans position against the bridged aryl plane. After activation by [Ph3C][B(C6F5)4], all the rare-earth metal complexes served as efficient catalysts for isoprene polymerization, producing polymers with high cis-1,4 regularity (up to 96.1%) and high molecular weight. The steric and electronic effects exerted on the active metal centers, as well as the radius of metal centers, were the major contributing factors for determining both the catalytic activity and cis-1,4-selectivity of the binuclear catalytic systems. Compared to its mononuclear analogue, the binuclear yttrium catalytic system with a para-phenyl bridge exhibited a higher thermostability and catalytic efficiency during polymerization, revealing a special binuclear effect in this binuclear catalytic system.

Tröger's Base-Based Cuboid Constructed by Chiral Self-Discrimination.

Cuboid, a basic geometric structure, has been widely applied in architecture and mathematics. In chemistry, the introduction of cuboid structures always provides a specific structural shape, enhances the stability of the structure and improves the performance of materials. Herein, a simple strategy exploiting self-discrimination to construct a cuboid-stacking crystal material is proposed, in which a chiral macrocycle (TBBP) based on Tröger's base (TB) and benzophenone (BP) was synthesized as the building element of the cuboid. The cuboid is designed to be transformable compared with cuboid structures in previous work. For this reason, it is considered that the cuboid-stacking structure can be transformed through external stimulation. Iodine vapor is selected as the external stimulus to transform the cuboid-stacking structure due to the favorable interaction between iodine and the cuboid. The changes in the stacking mode of TBBP is studied by single-crystal X-ray diffraction (SCXRD) and powder X-ray diffraction (PXRD). To our surprise, this Tröger's base-based cuboid shows strong iodine adsorption capacity up to 3.43 g g-1 and exhibits potential as a crystal material for iodine adsorption.

Effective Iodine Capture Behavior by a Censer-shaped Macrocycle in Vapor Phase and Aqueous Solution.

Iodine capture is of great significance for disposal of the hazardous radioactive iodine. CTX[P(O)Ph], one kind of censer-shaped macrocycle cyclotrixylohydroquinoylene (CTX) derivatives, was applied as an efficient iodine adsorbent. It showed satisfactory iodine adsorption capacity in vapor phase and could be reused without obvious adsorption capacity loss. Besides, the adsorbent could also uptake iodine in water. Fortunately, two iodine loading CTX[P(O)Ph] crystal structures were obtained under different conditions to explore the mechanism of iodine adsorption. This work provides a relatively rare example of iodine adsorption by macrocycle. It is promising that the results with crystal information might be meaningful for exploring and designing new kinds of iodine adsorbents.

The role of ferroptosis in acute lung injury.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a common disease with high morbidity and mortality, and its pathogenesis is believed to be related to oxidative stress, apoptosis, inflammation, and hypoxia. Ferroptosis is a type of nonapoptotic cell death characterized by iron-dependent lipid peroxide accumulation and is involved in many cellular physiological processes. Recent studies have confirmed that ferroptosis may be involved in the development of ALI. This review summarizes the most recent discoveries on the role of ferroptosis in ALI to provide new strategies for its prevention and treatment.

Tetradentate Pt(II) Complexes with Peripheral Hindrances for Highly Efficient Solution-Processed Blue Phosphorescent OLEDs.

Two tetradentate Pt(II) complexes with peripheral bulky-group hindrances [Pt(pzpyOczpy-B1) and Pt(pzpyOczpy-B2)] were synthesized and fully investigated for their structural and blue phosphorescent properties. Both X-ray crystallography and computational simulation revealed that bulky substituents incorporated into the C-pyrazolyl and C-pyridinyl positions lie out of the cyclometallated plane, thus alleviating the intramolecular distortions as well as reducing the intermolecular interaction in the solid state. In dichloromethane, their emission peaks at 460 nm with a narrow full width at half-maximum (FWHM) of less than 50 nm, and the photoluminescent quantum yields are over 95% with short decay lifetimes (<5 µs). Solution-processed blue devices are fabricated based on the two complexes. Device A based on Pt(pzpyOczpy-B1) shows excellent electroluminescent performances with the maximum current efficiency, power efficiency, and external quantum efficiency of 47.0 cd/A, 24.6 lm/W, and 22.9%, respectively. The understanding on inert peripheral hindrances provides an effective approach to designing Pt(II) complexes for high-quality blue phosphorescent emitters.

The performance of detecting Mycobacterium tuberculosis complex in lung biopsy tissue by metagenomic next-generation sequencing.

BACKGROUND: Tuberculosis (TB) is a chronic infectious disease caused by the Mycobacterium tuberculosis complex (MTBC), which is the leading cause of death from infectious diseases. The rapid and accurate microbiological detection of the MTBC is crucial for the diagnosis and treatment of TB. Metagenomic next-generation sequencing (mNGS) has been shown to be a promising and satisfying application of detection in infectious diseases. However, relevant research about the difference in MTBC detection by mNGS between bronchoalveolar lavage fluid (BALF) and lung biopsy tissue specimens remains scarce. METHODS: We used mNGS to detect pathogens in BALF and lung biopsy tissue obtained by CT-guide percutaneous lung puncture (CPLP) or radial endobronchial ultrasound transbronchial lung biopsy (R-EBUS-TBLB) from 443 hospitalized patients in mainland China suspected of pulmonary infections between May 1, 2019 and October 31, 2021. Aim to evaluate the diagnostic performance of mNGS for detecting MTBC and explore differences in the microbial composition in the 2 specimen types. RESULTS: Among the 443 patients, 46 patients finally were diagnosed with TB, of which 36 patients were detected as MTBC positive by mNGS (8.93%). Striking differences were noticed in the higher detection efficiency of lung biopsy tissue compared with BALF (P = 0.004). There were no significant differences between the 2 specimen types in the relative abundance among the 27 pathogens detected by mNGS from the 36 patients. CONCLUSIONS: This study demonstrates that mNGS could offer an effective detection method of MTBC in BALF or lung tissue biopsy samples in patients suspected of TB infections. When it comes to the situations that BALF samples have limited value to catch pathogens for special lesion sites or the patients have contraindications to bronchoalveolar lavage (BAL) procedures, lung biopsy tissue is an optional specimen for MTBC detection by mNGS. However, whether lung tissue-mNGS is superior to BALF-mNGS in patients with MTBC infection requires further prospective multicenter randomized controlled studies with more cases.

Genome-Wide Identification of Metal Tolerance Protein Genes in Populus trichocarpa and Their Roles in Response to Various Heavy Metal Stresses.

Metal tolerance proteins (MTPs) are plant divalent cation transporters that play important roles in plant metal tolerance and homeostasis. Poplar is an ideal candidate for the phytoremediation of heavy metals because of its numerous beneficial attributes. However, the definitive phylogeny and heavy metal transport mechanisms of the MTP family in poplar remain unknown. Here, 22 MTP genes in P. trichocarpa were identified and classified into three major clusters and seven groups according to phylogenetic relationships. An evolutionary analysis suggested that PtrMTP genes had undergone gene expansion through tandem or segmental duplication events. Moreover, all PtrMTPs were predicted to localize in the vacuole and/or cell membrane, and contained typical structural features of the MTP family, cation efflux domain. The temporal and spatial expression pattern analysis results indicated the involvement of PtrMTP genes in poplar developmental control. Under heavy metal stress, most of PtrMTP genes were induced by at least two metal ions in roots, stems or leaves. In addition, PtrMTP8.1, PtrMTP9 and PtrMTP10.4 displayed the ability of Mn transport in yeast cells, and PtrMTP6 could transport Co, Fe and Mn. These findings will provide an important foundation to elucidate the biological functions of PtrMTP genes, and especially their role in regulating heavy metal tolerance in poplar.

[Discussion on safety evaluation and risk control measures of Epimedii Folium].

Epimedii Folium,a commonly used traditional Chinese medicine,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism. However,in recent years,the number of reports on adverse reactions of Epimedii Folium and its Chinese patent medicines such as Xianling Gubao Capsules and Zhuanggu Guanjie Pills has been gradually increased,and the toxicity of Epimedii Folium has attracted more and more attention. In this article,the ancient and modern literature on Epimedii Folium was traced through a comprehensive and systematic literature analysis method. According to the 2015 edition of the Chinese Pharmacopoeia,Epimedii Folium refers to the dried leaves of Epimedii Folium brevicomu,E. sugittutum,E. pubescens or E. koreuuum. The Chinese Pharmacopoeia also includes E. wushanense of Wushan Epimedium,which is the same plant variety as Epimedium. The study showed that there were differences in the geographical distribution,composition and toxicity among five species of Epimedium. This paper also explained the toxicity mechanism as well as efficacy enhancing and toxicity reducing effects of Epimedii Folium,and reported its related adverse reaction cases. Through a retrospective comparative study on the toxicity of the modern Chinese patent medicines Xianling Gubao Capsules and Zhuanggu Guanjie Pills containing Epimedii Folium,it was believed that Epimedii Folium had cardiovascular system toxicity,neurotoxicity,hepatotoxicity,long-term toxicity,acute toxicity,genotoxicity and special toxicity; its safe medication factors included patient syndrome,doctor factors,drug factors,processing and compatibility factors. Meanwhile,strategies were proposed to improve patient safety medication awareness,standardize Epimedii Folium varieties and quality supervision,and the toxicity of Epimedii Folium was studied,hoping to draw attention from scholars to the safety of Epimedii Folium,improve the safe use of Epimedii Folium,and prevent adverse reactions.

LncRNA-DANCR contributes to lung adenocarcinoma progression by sponging miR-496 to modulate mTOR expression.

Long non-coding RNAs (lncRNAs) have emerged as new and important regulators of pathological processes including tumour development. In this study, we demonstrated that differentiation antagonizing non-protein coding RNA (DANCR) was up-regulated in lung adenocarcinoma (ADC) and that the knockdown of DANCR inhibited tumour cell proliferation, migration and invasion and restored cell apoptosis rescued; cotransfection with a miR-496 inhibitor reversed these effects. Luciferase reporter assays showed that miR-496 directly modulated DANCR; additionally, we used RNA-binding protein immunoprecipitation (RIP) and RNA pull-down assays to further confirm that the suppression of DANCR by miR-496 was RISC-dependent. Our study also indicated that mTOR was a target of miR-496 and that DANCR could modulate the expression levels of mTOR by working as a competing endogenous RNA (ceRNA). Furthermore, the knockdown of DANCR reduced tumour volumes in vivo compared with those of the control group. In conclusion, this study showed that DANCR might be an oncogenic lncRNA that regulates mTOR expression through directly binding to miR-496. DANCR may be regarded as a biomarker or therapeutic target for ADC.

miR-34b-5p inhibition attenuates lung inflammation and apoptosis in an LPS-induced acute lung injury mouse model by targeting progranulin.

Inflammation and apoptosis play important roles in the initiation and progression of acute lung injury (ALI). Our previous study has shown that progranulin (PGRN) exerts lung protective effects during LPS-induced ALI. Here, we have investigated the potential roles of PGRN-targeting microRNAs (miRNAs) in regulating inflammation and apoptosis in ALI and have highlighted the important role of PGRN. LPS-induced lung injury and the protective roles of PGRN in ALI were first confirmed. The function of miR-34b-5p in ALI was determined by transfection of a miR-34b-5p mimic or inhibitor in intro and in vivo. The PGRN level gradually increased and subsequently significantly decreased, reaching its lowest value by 24 hr; PGRN was still elevated compared to the control. The change was accompanied by a release of inflammatory mediators and accumulation of inflammatory cells in the lungs. Using bioinformatics analysis and RT-PCR, we demonstrated that, among 12 putative miRNAs, the kinetics of the miR-34b-5p levels were closely associated with PGRN expression in the lung homogenates. The gain- and loss-of-function analysis, dual-luciferase reporter assays, and rescue experiments confirmed that PGRN was the functional target of miR-34b-5p. Intravenous injection of miR-34b-5p antagomir in vivo significantly inhibited miR-34b-5p up-regulation, reduced inflammatory cytokine release, decreased alveolar epithelial cell apoptosis, attenuated lung inflammation, and improved survival by targeting PGRN during ALI. miR-34b-5p knockdown attenuates lung inflammation and apoptosis in an LPS-induced ALI mouse model by targeting PGRN. This study shows that miR-34b-5p and PGRN may be potential targets for ALI treatments.

Pillarurilarenes: Glycoluril-Expanded Pillararenes.

Glycoluril-expanded pillararenes composed of glycoluril and dialkoxybenzene units, namely, pillarurilarenes (PURA), were synthesized through a fragment coupling macrocyclization strategy. Partial replacement of dialkoxybenzene with glycoluril endows PURA with polarized equatorial methine protons for derivatization or CH-anion binding. Crystal structures of pillar[2]uril[4]arene and pillar[1]uril[4]arene containing two glycoluril units and one glycoluril unit, respectively, indicated the inward orientation of the glycoluril unit, as also suggested by 1H nuclear magnetic resonance and density functional theory calculation. This work lays a good foundation for expanding pillararenes using non-aromatic rings.

Dynasore Alleviates LPS-Induced Acute Lung Injury by Inhibiting NLRP3 Inflammasome-Mediated Pyroptosis.

Background: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are clinically severe respiratory disorders without available pharmacological therapies. Dynasore is a cell-permeable molecule that inhibits GTPase activity and exerts protective effects in several disease models. However, whether dynasore can alleviate lipopolysaccharide (LPS)-induced ALI is unknown. This study investigated the effect of dynasore on macrophage activation and explored its potential mechanisms in LPS-induced ALI in vitro and in vivo. Methods: Bone marrow-derived macrophages (BMDMs) were activated classically with LPS or subjected to NLRP3 inflammasome activation with LPS+ATP. A mouse ALI model was established by the intratracheal instillation (i.t.) of LPS. The expression of PYD domains-containing protein 3 (NLRP3), caspase-1, and gasdermin D (GSDMD) protein was detected by Western blots. Inflammatory mediators were analyzed in the cell supernatant, in serum and bronchoalveolar lavage fluid (BALF) by enzyme-linked immunosorbent assays. Morphological changes in lung tissues were evaluated by hematoxylin and eosin staining. F4/80, Caspase-1 and GSDMD distribution in lung tissue was detected by immunofluorescence. Results: Dynasore downregulated nuclear factor (NF)-κB signaling and reduced proinflammatory cytokine production in vitro and inhibited the production and release of interleukin (IL)-1ß, NLRP3 inflammasome activation, and macrophage pyroptosis through the Drp1/ROS/NLRP3 axis. Dynasore significantly reduced lung injury scores and proinflammatory cytokine levels in both BALF and serum in vivo, including IL-1ß and IL-6. Dynasore also downregulated the co-expression of F4/80, caspase-1 and GSDMD in lung tissue. Conclusion: Collectively, these findings demonstrated that dynasore could alleviate LPS-induced ALI by regulating macrophage pyroptosis, which might provide a new therapeutic strategy for ALI/ARDS.

Comparison of one-step laparoscopy and two-step endolaparoscopy in the treatment of secondary choledocholithiasis: A multicenter retrospective clinical study.

BACKGROUND: There are two minimally invasive ways of treating cholecystolithiasis combined with choledocholithiasis, but there remains some controversy regarding which technique is better, since they both have advantages and disadvantages. The one-step method involves laparoscopic cholecystectomy, laparoscopic common bile duct exploration, and primary close (LC + LCBDE + PC), while the two-step procedure consists of endoscopic retrograde cholangiopancreatography, endoscopic sphincterotomy, and laparoscopic cholecystectomy (ERCP + EST + LC). OBJECTIVE: This multicenter retrospective study aimed to analyze and compare the effects of the two techniques. METHODS: The data of patients who underwent either one-step LCBDE + LC + PC or two-step ERCP + EST + LC treatment for gallstones in the gallbladder and bile duct at the Shanghai Tenth People's Hospital, Shanghai Tongren Hospital, and Taizhou Fourth People's Hospital between January 1, 2015 and December 31, 2019 were collected, and the preoperative indicators of the two groups were compared. RESULTS: The surgical success rate of the one-step laparoscopic group was 96.23% (664/690), the transit abdominal opening rate was 2.03% (14/690), and there were 21 cases of postoperative bile leakage. The success rate of the two-step endolaparoscopic surgery was 78.95% (225/285), the transit opening rate was 2.46% (7/285), and there were 43 postoperative cases of pancreatitis and five of cholangitis. Postoperative cholangitis, pancreatitis, postoperative stone recurrence, postoperative hospitalization, and treatment costs were significantly lower (P< 0.05) in the one-step laparoscopic group than in the two-step endolaparoscopic group. However, the amount of intraoperative bleeding, the postoperative extraction time of the abdominal drainage tube, and the incidence of bile leakage were higher (P< 0.05) in the one-step laparoscopic group than in the two-step endolaparoscopic group. CONCLUSION: The two methods of treating choledocholithiasis combined with choledocholithiasis that were analyzed in this study were safe and effective, and each method had its own advantages.

Synthesis of Tröger's base-based [3]arenes for efficient iodine adsorption.

Enantiomers of Tröger's base-based [3]arenes R6N-E[3] and S6N-E[3] were synthesized successfully as two optically pure Tröger's base-based macrocycles in which three Tröger's base subunits were incorporated. Among these Tröger's base-based[3]arenes, M[3] showed high absorption of iodine up to 4.02 g g-1 in vapor.

Host-guest system of a phosphorylated macrocycle assisting structure determination of oily molecules in single-crystal form.

X-ray crystallography is the most reliable method for structure elucidation and absolute configuration determination of organic molecules based on their single-crystal forms. However, many analytes are hard to crystallize because of their low melting points (an oily state at room temperature) or conformational flexibility. Here, we report the crystallization of a macrocycle, CTX[P(O)Ph] (host), which is a cyclotrixylohydroquinoylene (CTX) derivative, with 26 oily organic molecules (guests), which is applied for the structural determination of the guest with X-ray crystallography. With the aid of the host, CTX[P(O)Ph], the guest molecules were well-ordered with full occupancy in crystal structures. In most cases, at least one guest structure without any disorder could be observed; solvent masking was not necessary for the single crystal X-ray structural analysis, and thus the structures of the guests could be successfully determined, and the absolute configuration could be assigned reliably for chiral guests with this method. The crystallization mechanism was further discussed from theoretical and experimental perspectives, suggesting that the negative electrostatic potential surface of CTX[P(O)Ph] and noncovalent interactions between the host and guest were crucial for the ordered arrangements of the guest.

Mutational spectrum for guiding the decision of adjuvant treatment in patients with resected biliary tract carcinoma.

BACKGROUND: Systemic chemotherapy or chemoradiation therapy has proven to be effective in treating advanced biliary tract carcinoma (BTC). However, its efficacy in the adjuvant setting remains controversial. Therefore, this study aimed to determine the prognostic significance of genomic biomarkers in resected BTC and their potential role in stratifying patients for adjuvant treatment. METHODS: We retrospectively reviewed 113 BTC patients who underwent curative-intent surgery and had available tumor sequencing data. Disease-free survival (DFS) was the primary outcome examined and univariate analysis was used to identify gene mutations with prognostic value. Favorable and unfavoratble gene subsets were distinguished from the selected genes through grouping, respectively. Multivariate Cox regression was used to identify independent prognostic factors of DFS. RESULTS: Our results indicated that mutations in ACVR1B, AR, CTNNB1, ERBB3, and LRP2 were favorable mutations, while mutations in ARID1A, CDKN2A, FGFR2, NF1, NF2, PBRM1, PIK3CA, and TGFBR1 were unfavorable mutations. In addition to age, sex, and node positive, favorable genes (HR = 0.15, 95% CI = 0.04-0.48, p = 0.001) and unfavorable genes (HR = 2.86, 95% CI = 1.51-5.29, p = 0.001) were identified as independent prognostic factors for DFS. Out of the 113 patients, only 35 received adjuvant treatment whereas the majority (78) did not. For patients with both favorable and unfavorable mutations undetected, adjuvant treatment showed negative effect on DFS (median DFS: S441 vs. 956 days, p = 0.010), but there was no significant difference in DFS among those in other mutational subgroups. CONCLUSIONS: Genomic testing might be useful in guiding the decisions regarding adjuvant treatment in BTC.

Anti-hyperglycemic effect of chebulagic acid from the fruits of Terminalia chebula Retz.

In the present study, we firstly compared rat intestinal α-glucosidase inhibitory activity by different ethanol-aqueous extractions from the dried fruits of Terminalia chebula Retz. The enzymatic assay showed that the 80% ethanol extract was more potent against maltase activity than both 50% and 100% ethanol extracts. By HPLC analysis, it was determined that the 80% ethanol extract had a higher content of chebulagic acid than each of 50% or 100% ethanol extract. Next, we investigated how efficiently chebulagic acid could inhibit sugar digestion by determining the glucose level on the apical side of the Caco-2 cell monolayer. The result showed that the maltose-hydrolysis activity was down-regulated by chebulagic acid, which proved to be a reversible inhibitor of maltase in Caco-2 cells. On the other hand, chebulagic acid showed a weak inhibition of sucrose-hydrolysis activity. Meanwhile, chebulagic acid did not have an obvious influence on intestinal glucose uptake and was not effective on glucose transporters. Further animal studies revealed that the oral administration of chebulagic acid (100 mg/kg body weight) significantly reduced postprandial blood glucose levels by 11.1% in maltose-loaded Sprague-Dawley (SD) rats compared with the control group, whereas the oral administration of chebulagic acid did not show a suppressive effect on postprandial hyperglycemia in sucrose- or glucose-loaded SD-rats. The results presented here suggest that chebulagic acid from T. chebula can be used to control blood glucose and manage type 2 diabetes, although clinical trials are needed.

Metagenomic Next-Generation Sequencing Is Highly Efficient in Diagnosing Pneumocystis Jirovecii Pneumonia in the Immunocompromised Patients.

Purposes: To explore the value of metagenomic next-generation sequencing (mNGS) in diagnosing pneumocystis jiroveciipneumonia (PJP) in the immunocompromised patients. Methods: Data of 122 patients with PJP in an immunosuppressed state and 67 non-PJP patients were collected. The diagnostic efficacy of mNGS was compared with the conventional methods, including Gomori methenamine silver (GMS) staining and serum (1,3)-ß-D-glucan (BDG). Changes of anti-microbial therapy for patients with PJP based on mNGS results were also reviewed. Results: The diagnostic sensitivity of mNGS to PJP was higher than that of GMS and BDG (100% vs. 15 and 74.5%, p < 0.001). The diagnostic specificity (91.%) was lower than that of GMS (100%), and similar with BDG (89.6%). In addition to P. jirovecii, mNGS revealed co-pathogens like human ß-herpesvirus 5, human γ-pesvirus 4, and some other opportunistic pathogens. The reads of mNGS were remarkably higher in BALF than in blood samples. Initial antimicrobial treatment was modified in 89.3% patients based on the mNGS results, and 74 cases (60.7%) were treated with anti-P. jirovecii therapy. Conclusion: mNGS is highly efficient in diagnosing PJP and good at identifying pathogens in mixed infections.

Overexpression of FAM83A Is Associated with Poor Prognosis of Lung Adenocarcinoma.

Family with sequence similarity 83, member A (FAM83A) plays an essential and fundamental role in the proliferation, progression, and apoptosis of many malignant tumors, including lung cancer. This study aimed to determine the expression pattern of FAM83A in lung adenocarcinoma (LUAD) and its correlation with the prognosis of cancer and the survival of the patients. Bioinformatics analysis, immunohistochemistry, and Western blotting were used to explore and detect the expression of FAM83A in LUAD cells. The mechanism of FAM83A in proliferation and migration was examined. The correlation between FAM83A expression and survival rate was assessed by the Kaplan-Meier and Cox regression. FAM83A expression was elevated in LUAD tissues and was related to shorter overall survival (P < 0.05). A significant increase in FAM83A protein was observed in the LUAD tissue (P < 0.05). Compared with patients with early-stage tumors (stage I-II), those with advanced stage tumors (stage III-IV) had significantly higher FAM83A expression levels (P < 0.05). Downregulation of FAM83A led to a reduction in cell proliferation, a decrease in migration ability, and diminished epithelial-mesenchymal transition (EMT) in the lung cancer cell lines. Overexpression of FAM83A was associated with early lymph node metastasis and poor overall survival among LUAD patients. The findings indicated that FAM83A may play a critical role in promoting the LUAD progression and thus might serve as a novel prognostic marker in LUAD.

[Effects of Zhongfeng capsule on autophagy related proteins expressions of brain tissue in rats with cerebral ischemia/reperfusion injury].

Objective: To investigate the effects of Zhongfeng capsule on the autophagy-related proteins expression in rats with cerebral ischemia/reperfusion injury (CI/ RI), and to explore its neural protection mechanisms of the decoction. Methods: Rat middle cerebral artery ischemia/reperfusion injury model (ischemia for 2 h, reperfusion for 24 h) was prepared by the improved line plug method. Sixty male SD rats were randomly divided into sham operation group, model group, butylphthalide group(0.054 g/kg), Zhongfeng capsule high-dose groups (1.08 g/kg), Zhongfeng capsule middle-dose groups (0.54 g/kg), Zhongfeng capsule low-dose groups (0.27 g/kg), with 10 rats in each group. Rats were treated with Zhongfeng capsule by gavage once a day for 10 days. The rats were sacrificed and the brain tissue was obtained after the experiment in each group. Score neurological deficit was evaluated after 24 h of the last intervention in rat of each group. The pathological changes of brain tissue were observed by HE staining. The serum levels of estradiol (E2) and follicle stimulating hormone (FSH) were determined by ELISA. The expressions of key genes and proteins of PI3K/Akt/Beclin1 signaling pathway in brain tissue were detected by qRT-PCR and Western blot respectively. Results: Compared with the sham operation group, the body weight and protein expressions of p-PI3k and p-Akt in brain tissue of rats were decreased significantly in the model group, while the brain index, neurological deficit score, gene and protein expressions of Beclin1 and LC3 were increased markedly in the model group(P＜0.05 or P＜0.01). In the model group, nerve cells of brain tissue were loosely packed, interstitial edema, triangular in shape, nuclear pyknosis and dark-blue staining were observed. Compared with the model group, the body weight of rats was increased obviously, the neurological deficit score was decreased significantly and the pathological injury of brain tissue was alleviated evidently in high-dose of Zhongfeng capsule group (P＜0.05). The brain index, the gene and protein expressions of Beclin1 and LC3 were decreased apparently in Zhongfeng capsule treatment groups(P＜0.05 or P＜0.01), while the expressions of p-PI3k and p-Akt in brain tissue were increased evidently in Zhongfeng capsule treatment groups(P＜0.05 or P＜0.01). Conclusion: Zhongfeng capsule can inhibit autophagy and improve brain neurons lesion of CIRI rats, the mechanism may be related to regulate the expression of Beclin1 and LC3 in PI3K/Akt/Beclin1 signaling pathway.