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Background China has been using inactivated coronavirus disease 2019 (COVID-19) vaccines as primary series and booster doses to protect the population from severe to fatal COVID-19. We evaluated primary and booster vaccine effectiveness (VE) against Omicron BA.2 infection outcomes. Methods This was a 13-province retrospective cohort study of quarantined close contacts of BA.2-infected individuals. Outcomes were BA.2 infection, COVID-19 pneumonia or worse, and severe/critical COVID-19. Absolute VE was estimated by comparison with an unvaccinated group. Results There were 289 427 close contacts ≥3 years old exposed to Omicron BA.2 cases; 31 831 turned nucleic acid amplification test–positive during quarantine, 97.2% with mild or asymptomatic infection, 2.6% with COVID-19 pneumonia, and 0.15% with severe/critical COVID-19. None died. Adjusted VE (aVE) against any infection was 17% for primary series and 22% when boosted. Primary series aVE in adults >18 years was 66% against COVID-19 pneumonia or worse and 91% against severe/critical COVID-19. Booster dose aVE was 74% against pneumonia or worse, and 93% against severe/critical COVID-19. Conclusions Inactivated COVID-19 vaccines provided modest protection from infection, very good protection against pneumonia, and excellent protection against severe/critical COVID-19. Booster doses are necessary to provide strongest protection.

Signal transduction pathways mediated by sensor histidine kinases and cognate response regulators control a variety of physiological processes in response to environmental conditions in most bacteria. Comparatively little is known about the mechanism(s) by which single-domain response regulators (SD-RRs), which lack a dedicated output domain but harbour a phosphoryl receiver domain, exert their various regulatory effects in bacteria. Here we have examined the role of the SD-RR proteins encoded by the phytopathogen Xanthomonas campestris pv. campestris (Xcc). We describe the identification and characterization of a SD-RR protein named McvR (motility, chemotaxis, and virulence-related response regulator) that is required for virulence and motility regulation in Xcc. Deletion of the mcvR open reading frame caused reduced motility, chemotactic movement, and virulence in Xcc. Global transcriptome analyses revealed the McvR had a broad regulatory role and that most motility and pathogenicity genes were down-regulated in the mcvR mutant. Bacterial two-hybrid and protein pull-down assays revealed that McvR did not physically interact with components of the bacterial flagellum but interacts with other SD-RR proteins (like CheY) and the subset of DNA-binding proteins involved in gene regulation. Site-directed mutagenesis and phosphor-transfer experiments revealed that the aspartyl residue at position 55 of the receiver domain is important for phosphorylation and the regulatory activity of McvR protein. Taken together, the findings describe a previously unrecognized class of SD-RR protein that contributes to the regulation of motility and virulence in Xcc.

Paraquat is one of the most widely used nonselective herbicides and has elicited the emergence of paraquat-resistant weeds. However, the molecular mechanisms of paraquat resistance are not completely understood. Here we report the Arabidopsis gain-of-function mutant pqt15-D with significantly enhanced resistance to paraquat and the corresponding gene PQT15, which encodes the Multidrug and Toxic Extrusion (MATE) transporter DTX6. A point mutation at +932 bp in DTX6 causes a G311E amino acid substitution, enhancing the paraquat resistance of pqt15-D, and overexpression of DTX6/PQT15 in the wild-type plants also results in strong paraquat resistance. Moreover, heterologous expression of DTX6 and DTX6-D in Escherichia coli significantly enhances bacterial resistance to paraquat. Importantly, overexpression of DTX6-D enables Arabidopsis plants to tolerate 4 mM paraquat, a near-commercial application level. DTX6/PQT15 is localized in the plasma membrane and endomembrane, and functions as a paraquat efflux transporter as demonstrated by paraquat efflux assays with isolated protoplasts and bacterial cells. Taken together, our results demonstrate that DTX6/PQT15 is an efflux transporter that confers paraquat resistance by exporting paraquat out of the cytosol. These findings reveal a molecular mechanism of paraquat resistance in higher plants and provide a promising candidate gene for engineering paraquat-resistant crops.

Background Coarctation of the aorta (CoA) is the most common undiagnosed congenital heart defect during prenatal screening. High false positive and false negative rates seriously affect prenatal consultation and postnatal management. The objective of the study was to assess the utility of various measurements to predict prenatal CoA and to derive a diagnostic algorithm. Methods One hundred and fifty-four fetuses with suspected CoA who presented at Fuwai Hospital between December 2017 and August 2021 were enrolled and divided into confirmed CoA cases (47) and false-positive cases (107), according to their postnatal outcomes. Fetal echocardiographic measurements included the cardiac chambers sizes, valve annular diameters, and ascending aorta and pulmonary artery dimensions. The corresponding gestational age-related Z-scores were collected. The diameter of the transverse aortic arch and the aortic isthmus were measured. The TAO-DAO angle between the transverse aortic arch and isthmus was also measured. The receiver operating characteristic curve determined the predictive capability of each diagnostic parameter, and the kappa test determined the diagnostic accuracy of the proposed model.Results Confirmed CoA cases had thinner transverse arches (1.92 ± 0.32 mm vs. 3.06 ± 0.67 mm, P = 0.0001), lower Z-scores of the isthmus (-8.97 ± 1.45 vs. -5.65 ± 1.60, P = 0.0001), smaller TAO-DAO angles (105.54 ± 11.51° vs. 125.29 ± 8.97°, P = 0.0001) and larger distance between the left subclavian artery and left common carotid artery (4.45 ± 1.75 mm vs. 2.74 ± 1.07 mm, P = 0.0001) than the false-positive cases. The area under the curve was 0.947 (95% CI 0.91–0.98) for the TAO-DAO angle, 0.942 (95% CI 0.91–0.98) for the transverse arch diameter, and 0.937 (95% CI 0.90–0.98) for the Z-score of the isthmus. Three important echocardiographic indices were combined to derive a three-step echocardiographic diagnostic model. The kappa test showed that the model’s diagnostic accuracy was consistent with postnatal outcomes (kappa value 0.936, P = 0.0001).Conclusions The three step approach included the three most useful measurements and the five additional indices with appropriate cut-off values. The algorithm optimizes the diagnosis of fetal CoA and is clinically feasible.Trial registration: retrospectively registered.

Kadsura heteroclita (Roxb) Craib stem (KHS) is a medicinal plant used for the treatment of rheumatism arthritis diseases in Tujia ethnomedicine. Thus far, the complex chemical compositions in KHS are not clear, and the levels of the major compounds in KHS are not well understood. In this study, a novel UHPLC-Q-Orbitrap HRMS method was established for the simultaneous quali-quantitative analysis of KHS. A total of 204 compounds were identified, including triterpenoids, lignans, sesquiterpenes, fatty acids, phenolic acids, and flavonoids, more than 100 of which were first discovered in KHS. Using the same method, 12 representative bioactive components were successfully quantified. The method was fully validated by linearity, LOD, LOQ, precision, stability, recovery, and matrix effects, and it was applied to quantify the 12 representative compounds in 4 batches of KHS. As this method enables retrospective data analysis and has no upper limit to the number of analytes in a single run, it can be applied to quantify more active components of KHS in the future.

Background: Huangqi Guizhi Wuwu decoction (HQGZWW) exhibits good effects when administered to treat multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Understanding the precise mechanism of this decoction is thus important. Based on the findings of our previous study, the aim of the present study was to understand the role of antigen-specific CD8+ T-cells on the pathogenesis of MS/EAE when HQGZWW is administered as treatment. Methods: Myelin oligodendrocyte glycoprotein (MOG) 35-55-induced mice were administered distilled water, prednisone, and high dose or low dose HQGZWW. After purified CD4+ and CD8+ T-cells were stimulated with the MOG35-55 peptide, proliferation and cytokine secretion assays were performed. To establish the adoptive transfer EAE model, naive mice were injected with MOG35-55 -CD8+ or CD4+ T-cells. Results: Significant improvements in EAE score and pathology were observed in the high dose HQGZWW and prednisone groups. Compared to the low dose HQGZWW and distilled water groups, lower antigen-specific responses, lower levels of interferon-gamma, and higher levels of interleukin (IL)-4 and IL-10 from CD8+ and CD4+ T cells were observed in the high dose HQGZWW and prednisone groups. Finally, the EAE score was observed to be similar between the high dose HQGZWW group and prednisone group; however, this finding was not observed in the low dose HQGZWW group. Conclusion: Our findings suggest that high dose HQGZWW has similar effects on cell proliferation, cytokine secretion, and EAE score to prednisone, while low dose HQGZWW does not have such effect. The protective role of HQGZWW against EAE might thus depend on the Th2 cytokine secretion profile induced by either MOG35-55 specific CD8+ or CD4+ T-cells.

BACKGROUND: Mitochondrial transcription elongation factor (TEFM) is an essential molecule that regulates the replication-transcription switch of mitochondrial DNA. TEFM modulates both transcription elongation and RNA processing in mitochondria. The purpose of the present study was to determine the association of TEFM with tumor progression and prognosis in hepatocellular carcinoma (HCC) patients. METHODS: The different protein expression level of TEFM among HCC cell lines was detected by Western blotting. The gene expression profiling interactive analysis (GEPIA) was used to dynamically analyze the mRNA expression of TEFM gene in different stages of HCC. The protein and mRNA expression levels of TEFM were detected by immunohistochemistry, Western blotting and qRT-PCR. The mRNA-SeqV2 expression of TEFM and clinical information of HCC patients were downloaded from the TCGA database by using R3.6.3 software. Next, the relationships between the expression level of TEFM and clinicopathological characteristics and the prognostic value of TEFM were analyzed. A Cox regression model was used for multivariate analysis of the factors that affected the prognosis of HCC. Finally, the association between the expression levels of TEFM and other mitochondrial regulatory genes and HCC biomarker genes was analyzed by GEPIA. RESULTS: TEFM is upregulated in HCC cell lines compared to noncancerous liver cell line. TEFM protein and mRNA expression levels in HCC tissues were significantly upregulated compared with those in noncancerous liver tissues. In addition, the mRNA expression level of TEFM was significantly correlated with sex, serum AFP level, and vascular invasion (P0). CONCLUSIONS: Our findings reveal that TEFM may play an important role in the progression of HCC. More importantly, the elevated expression of TEFM may potentially predict poor overall survival (OS) and disease-free survival (DFS) in patients with HCC.

With the rapid development of artificial intelligence, in order to solve the problems of many questions from trainees, poor efficiency of teachers in answering questions and high work intensity in the process of thermal power plant simulation practice, this paper proposes an intelligent training expert guidance system for thermal power plant simulation, and this paper uses Visual C++ software programming to implement an intelligent training expert guidance system with voice interaction and video presentation functions, using the speech development package Microsoft Speech SDK, in-depth study of the SAPI it provides, design and implementation of speech recognition function and speech synthesis function. The XML file is used to define the types of questions and the corresponding Q&A test statements for keyword extraction; the video presentation function is realized with the help of Windows Media Player. The test results show that, based on the successful speech recognition, the system can simulate the way of dialogue between teachers and learners and answer learners’ questions in real time. The system has an open function, users can add questions independently, expand the database in real time, jump out of the traditional limitations of space, time and geography, and increase the interest of learning.

The cytoplasmic polyadenylation element-binding (CPEB) protein family have demonstrated a crucial role for establishing synaptic plasticity and memory in model organisms. In this review, we outline evidence for CPEB3 as a crucial regulator of learning and memory, citing evidence from behavioral, electrophysiological and morphological studies. Subsequently, the regulatory role of CPEB3 is addressed in the context of the plasticity-related proteins, including AMPA and NMDA receptor subunits, actin, and the synaptic scaffolding protein PSD95. Finally, we delve into some of the more well-studied molecular mechanisms that guide the functionality of this dynamic regulator both during synaptic stimulation and in its basal state, including a variety of upstream regulators, post-translational modifications, and important structural domains that confer the unique properties of CPEB3. Collectively, this review offers a comprehensive view of the regulatory layers that allow a pathway for CPEB3’s maintenance of translational control that guides the necessary protein changes required for the establishment and maintenance of lasting synaptic plasticity and ultimately, long term learning and memory.

Objective Due to the resistance of cancer cells, chemotherapy has been severely restricted. Docosahexaenoic acid (DHA) has been broadly identified as the chemo-sensitizing agent and revertant of multidrug resistance owing to its pleiotropic characteristics; however, it has not been well interpreted. The purpose of this research was to identify the anticancer role of DHA and its combination with the chemotherapeutic agent Gefitinib in non-small cell lung cancer (NSCLC). Methods Human chemo-sensitive NSCLC PC-9 cells and the Gefitinib-resistant counterpart PC-9/GR cells were adopted to assess the effects of the integrated DHA and Gefitinib treatments in vitro and vivo, for which the combination index (CI), apoptosis rate and the epithelial growth factor receptor (EGFR) pathway were analyzed. Results Comparing with the control cells, the DHA-treated PC-9/GR cells triggered the increase of drug absorption and sensitivity, suggesting that the sensitivity of chemotherapeutic drug could be induced by DHA. Moreover, the elevation of phosphorylation levels of EGFR and the downstream extracellular signal-regulated kinase (ERK) in the cellular lysates were induced by the DHA+Gefitinib treatment. Additionally, the long-term Gefitinib stimulated PC-9 model revealed that DHA could revert the Gefitinib resistance. Conclusion This is the first research that indicated the novel biochemical effect of DHA, which can help in overcoming the resistance of EGFR-TKI in NSCLC cells and broaden the horizon of the DHA supplementation during the NSCLC therapy.

The time-velocity integral of the left ventricular outflow tract (TVIThe aim of this study was to investigate the predictive value of baseline TVIA total of 225 consecutive patients with a diagnosis of incident PAH were prospectively studied and echocardiology-derived TVIDuring a median follow-up period of 33.8 months, 44 patients died of cardiovascular events. Baseline TVIThe findings of this study suggest that noninvasive TVI

Background: The Von Hippel-Lindau ( VHL ) p.Tyr98His ( Y98H ) mutation is designated as the “Black Forest” founder mutation and has been previously reported in Western countries. This study reports the first recorded Chinese VHL family with the “Black Forest” mutation in Asia. Methods: Paired whole-exome sequencing (WES), Sanger sequencing and immunohistochemistry (IHC) were performed on samples from a large Chinese family to confirm the causative mutation and mutation carriers in the family. Clinical manifestations of the family were summarized and compared with those reported from other patients with the VHL Y98H mutation. Results: The Chinese pheochromocytoma (PCC) family was identified as a VHL type 2 family with a Y98H mutation. There were 4 VHL patients and 11 currently healthy individuals with the mutation. Copy number analysis and SDHB IHC were performed to exclude interference from other pathogenic genes of PCC or paraganglioma (PGL). Conclusions: We report the first recorded instance of a Chinese VHL type 2 family with the “Black Forest” mutation by using WES and Sanger sequencing, which widens the currently recorded presence of the “Black Forest” mutation to China and potentially elsewhere in Asia and indicates that the “Black Forest” mutation does not uniquely evolve in occidental countries. A personalized surveillance approach, which may be more appropriate for affected families, has been recommended to improve quality of life.

Alteration in cellular energy metabolism plays a critical role in the development and progression of cancer. Leptin is a hormone secreted by adipose tissue. Recent reports have shown that leptin can induce cancer cell proliferation and regulate cell energy metabolism, but the regulatory mechanism is still unclear. Here, we showed that leptin could promote cell proliferation and maintain high adenosine triphosphate levels in HCT116 and MCF-7 cells. The expression levels of carnitine palmitoyl transferase 1A (CPT1A), pyruvate dehydrogenase, succinate dehydrogenase subunit A and mitochondrial respiratory chain-associated proteins NADH dehydrogenase 1 (ND1), NADH:ubiquinone oxidoreductase subunit B8, and mitochondrial transcription factor A (TFAM) were distinctly increased in leptin-treated HCT116 and MCF-7 cells, while fatty acid synthase and lactate dehydrogenase expression were downregulated. Simultaneously, we found that c-Myc and peroxisome proliferator-activated receptor gamma co-activator 1 (PGC-1) protein expression levels were significantly increased. These results indicated that leptin boosted fatty acid β-oxidation and the tricarboxylic acid cycle, enhanced oxidative phosphorylation (OXPHOS) activity, and inhibited fatty acid synthesis and glycolysis in tumor cells. Gene transfection experiments revealed that leptin could induce the expression of c-Myc. Moreover, the expressions of PGC-1, CPT1A, and TFAM proteins were downregulated in HCT116 cells with low expression of c-Myc, and the expression levels of these proteins were increased in HCT116 cells overexpressing c-Myc. These findings suggest that leptin plays an important role in the regulation of energy metabolism in tumor cells. It may regulate fatty acid oxidation and OXPHOS of tumor cells by regulating the c-Myc/PGC-1 pathway. Targeting metabolic pathways for cancer treatment has been investigated as potential preventive or therapeutic methods. This study has important implications for the clinical therapy of tumor cell metabolism through hormone regulation.

A previous study by our research group showed that sirtuin5 (SIRT5), a member of the class III NAD＋-dependent deacetylase family, is highly expressed in colorectal cancer (CRC). The present study showed that deletion of SIRT5 induced cell cycle arrest and apoptosis as a result of continuous and irreparable DNA damage in CRC cells, a consequence of the impaired production of ribose-5-phosphate (R5P) which is essential for nucleotide synthesis. Consistently, the cell cycle arrest and apoptosis induced by SIRT5 silencing could be reversed by supplementation with four nucleotides. Moreover, metabolic profiling revealed that silencing of SIRT5 could inhibit the non-oxidative pentose phosphate pathway (PPP), which produces R5P, required for base ribosylation. Notably, SIRT5 activates transketolase (TKT), the key enzyme in the cellular non-oxidative PPP, by mediating its lysine demalonylation through the interaction between SIRT5 and TKT. Furthermore, the results demonstrated that TKT is essential for the SIRT5-induced malignant phenotypes of CRC, both in vivo and in vitro. These results therefore revealed that the increased lysine malonylation levels of TKT caused by silencing SIRT5 suppresses non-oxidative pentose phosphate metabolism, leading to a low-nucleotide pool. This in turn induces DNA damage in tumor cells and inhibits proliferation, suggesting that SIRT5 may serve as a potential anticancer target.

Paraquat is one of the most widely used non-selective herbicides and has elicited the emergence of paraquat resistant weeds. However, the molecular mechanisms of paraquat resistance are not completely understood. Here we report an Arabidopsis gain-of-function mutant pqt15-D with significantly enhanced resistance to paraquat and the corresponding PQT15 encoding the MATE transporter DTX6. A point mutation at +932 bp in DTX6 causing the G311E amino acid residue change brings about the enhanced paraquat resistance of pqt15-D. Overexpression of DTX6/PQT15 in the wild type also confers strong paraquat resistance, whereas the DTX6/PQT15 knockout mutants exhibits hypersensitive phenotype to paraquat. Moreover, heterologous expression of DTX6 and DTX6-D in E. coli significantly enhances bacterial resistance to paraquat. DTX6/PQT15 mainly localizes in the plasma membrane as shown by DTX6-GFP and functions as a paraquat efflux transporter as demonstrated by paraquat efflux assays with isolated protoplasts and bacterial cells. Taken together, our results demonstrate that DTX6/PQT15 is an efflux transporter and confers paraquat resistance by exporting paraquat out of cytosol, therefore unraveling a molecular mechanism of paraquat resistance in higher plants and providing a promising candidate of generating paraquat resistance crops.

Recent studies show that intracellular accumulation of cholesterol leads to acquired resistance to gefitinib in non-small cell lung cancer (NSCLC) cells. In this study we investigated how to regulate the cholesterol levels in gefitinib-resistant NSCLC cells. We showed that intracellular cholesterol levels in gefitinib-resistant cell lines (PC-9/GR, H1975, H1650, and A549) were significantly higher than that in gefitinib-sensitive cell line (PC-9). Treatment with gefitinib (5 μM) significantly increased intracellular cholesterol levels in PC-9/GR, H1975, and H1650 cells. Gefitinib treatment downregulated the expression of PPARα, LXRα, and ABCA1, leading to dysregulation of cholesterol efflux pathway. We found that a lipid-lowering drug fenofibrate (20, 40 μM) dose-dependently increased the expression of PPARα, LXRα, and ABCA1, decreased the intracellular cholesterol levels, and enhanced the antiproliferative effects of gefitinib in PC-9/GR, H1975, and H1650 cells. We revealed that fenofibrate increased the gefitinib-induced apoptosis via regulating the key proteins involved in the intrinsic apoptosis pathway. In PC-9/GR, H1975 and H1650 cells, fenofibrate dose-dependently increased the expression of AMPK, FoxO1, and decreased the expression of AKT, which were remarkably weakened by knockdown of PPARα. In PC-9/GR cell xenograft mice, combined administration of gefitinib (25 mg · kg(−1) · d(−1)) and fenofibrate (100 mg · kg(−1) · d(−1)) caused remarkable inhibition on tumor growth as compared to treatment with either drug alone. All the results suggest that fenofibrate relieves acquired resistance to gefitinib in NSCLC by promoting apoptosis via regulating PPARα/AMPK/AKT/FoxO1 pathway. We propose that combination of gefitinib and fenofibrate is a potential strategy for overcoming the gefitinib resistance in NSCLC.

The enrichment of Enterotoxigenic Bacteroides fragilis (ETBF) has been identified in CRC patients and associated with worse prognosis. Cancer stem cells (CSCs) play essential roles in CRC development. However, whether ETBF is involved in CSCs regulation is unknown. To clarify the role of ETBF in CSCs properties, we performed extreme limited dilution assays (ELDA) in nude mice injected with ETBF-treated or untreated CRC cells subcutaneously, tumor organoids culture in azoxymethane (AOM) mouse model after gavaging with or without ETBF, and cell sphere formation assay after incubating CRC cell lines with or without ETBF. The results indicated that ETBF increased the stemness of CRC cells in vivo and in vitro. Furthermore, ETBF enhanced the expression of core stemness transcription factors Nanog homeobox (NANOG) and sex determining region Y-box 2 (SOX2). Histone H3 Lysine 9 trimethylation (H3K9me3) is critical in regulating CSCs properties. As an epigenetic and transcriptional regulator, JmjC-domain containing histone demethylase 2B (JMJD2B) is essential for embryonic stem cell (ESC) transformation and H3K9me3 demethylation. Mechanistically, ETBF infection significantly upregulated JMJD2B levels in CRC cell lines and nude mice xenograft model. JMJD2B epigenetically upregulated NANOG expression via demethylating its promoter H3K9me3, to mediate ETBF-induced stemness of CRC cells. Subsequently, we found that the Toll-like receptor 4 (TLR4) pathway, activated by ETBF, contributed to the enhanced expression of JMJD2B via nuclear transcription factor nuclear factor of activated T cells 5 (NFAT5). Finally, in human CRC samples, the amount of ETBF positively correlated with nuclear NFAT5, JMJD2B, and NANOG expression levels. In summary, ETBF upregulated JMJD2B levels in a TLR4-NFAT5-dependent pathway, and played an important role in stemness regulation, which promoted colorectal carcinogenesis.

Drought is one of the most important environmental factors limiting plant growth and productivity. The molecular mechanisms underlying plant drought resistance are complex and not yet fully understood. Here, we show that the Arabidopsis MADS-box transcription factor AGL16 acts as a negative regulator in drought resistance by regulating stomatal density and movement. Loss-of-AGL16 mutants were more resistant to drought stress and had higher relative water content, which was attributed to lower leaf stomatal density and more sensitive stomatal closure due to higher leaf ABA levels compared with the wild type. AGL16-overexpressing lines displayed the opposite phenotypes. AGL16 is preferentially expressed in guard cells and down-regulated in response to drought stress. The expression of CYP707A3 and AAO3 in ABA metabolism and SDD1 in stomatal development was altered in agl16 and overexpression lines, making them potential targets of AGL16. Using chromatin immunoprecipitation, transient transactivation, yeast one-hybrid, and electrophoretic mobility shift assays, we demonstrated that AGL16 was able to bind the CArG motifs in the promoters of the CYP707A3, AAO3, and SDD1 and regulate their transcription, leading to altered leaf stomatal density and ABA levels. Taking our findings together, AGL16 acts as a negative regulator of drought resistance by modulating leaf stomatal density and ABA accumulation.

Major depressive disorder takes at least 3 weeks for clinical anti‐depressants, such as serotonin selective reuptake inhibitors, to take effect, and only one‐third of patients remit. Ketamine, a kind of anaesthetic, can alleviate symptoms of major depressive disorder patients in a short time and is reported to be effective to treatment‐resistant depression patients. The rapid and strong anti‐depressant‐like effects of ketamine cause wide concern. In addition to ketamine, caloric restriction and sleep deprivation also elicit similar rapid anti‐depressant‐like effects. However, mechanisms about the rapid anti‐depressant‐like effects remain unclear. Elucidating the mechanisms of rapid anti‐depressant effects is the key to finding new therapeutic targets and developing therapeutic patterns. Therefore, in this review we summarize potential molecular and cellular mechanisms of rapid anti‐depressant‐like effects based on the pre‐clinical and clinical evidence, trying to provide new insight into future therapy.

Breast cancer is the most common malignancy in women, and metastasis is the leading cause of death in breast cancer patients. Previous studies have shown that epithelial‑mesenchymal transition (EMT) is involved in the metastasis of breast cancer, but the metabolic reprogramming and regulation mechanisms involved in the EMT process are still unclear. In the present study, we successfully constructed an EMT cell model induced by transforming growth factor β1 (TGF‑β1) treatment of MCF‑7 cells at different times. The results showed that cell adhesion decreased, cell invasion increased and ATP levels increased in EMT MCF‑7 cells treated with TGF‑β1. Furthermore, the expression of fatty acid synthase (FASN) was decreased, and the expression of key fatty acid β‑oxidation enzymes (CPT1 and CD36) was elevated in treated cells compared to control cells. These results showed that the fatty acid oxidation pathway was enhanced. In addition, the expression of NADH:ubiquinone oxidoreductase subunit B8 (NDUFB8), mitochondrial transcription factor A (TFAM) and cytochrome c oxidase subunit I (COXI) increased, and the mitochondrial DNA copy number and ROS levels were also significantly increased during TGF‑β1‑induced EMT. These results indicated that mitochondrial oxidative phosphorylation (OXPHOS) activity was enhanced during EMT. In addition, we observed that the expression of p‑AMPK was increased and ACC (Acetyl‑CoA Carboxylase) was decreased during TGF‑β1‑induced EMT in MCF‑7 cells. Immunohistochemical analysis of clinical samples revealed high expression of FASN in epithelial cells that had high expression of E‑cadherin, while high expression of CPT‑1 was observed in mesenchymal cells that had high expression of vimentin. Results of the current study showed a metabolic transition in TGF‑β1‑induced EMT in MCF‑7 cells. This transition may regulate fatty acid oxidation and OXPHOS activity in EMT MCF‑7 cells through the p‑AMPK pathway. These data suggest that a metabolic transition that suppresses lipogenesis and favors energy production is an essential component of TGF‑β1‑induced EMT and metastasis in breast cancer. This study thus provides a new strategy for identifying new therapeutic targets for breast cancer.

The preparation of highly pseudocapacitive electrode materials is important for development of supercapacitors. In this work, a kind of new electrode material, namely, hydrogen molybdenum bronze (HMB) modified polymolybdate-based metal–organic complex {Cu(3-H2bptzh)(H2O)2[γ-Mo8O26]}·(3-H2bptzh)·H2O (1) (1-HMB) was prepared by electrochemical treatment (3-bptzh = 1,4-bis(5-(3-pyridyl)tetrazolyl) -hexane), aiming for promoting the pseudocapability of polymolybdates-based complexes. The carbon cloth-based electrode with 1-HMB (1-HMB/CC-0.15), which was obtained through electrochemical treatment between potential range of − 0.15 and 0.5 V (vs. SCE) achieved a high specific capacitance of 807.2F g−1 at the current density of 1 A g−1. The active sites and the mixed valence brought by the amorphous HMB layer give rise to the improved pseudocapacitance. 1-HMB/CC-0.15 can maintain 89.7% of its initial capacitance after 5000 galvanostatic charge/discharge cycles. In order to probe the effect brought by the structure of complex precursor, two new polymolybdates-based complexes {Cu(3-H2bptzpe)2[γ-Mo8O26]} (2) and {Cu2(3-bptzp)2(H2O)4[γ-Mo8O26]} (3) (3-bptzpe = 1,4-bis(5-(3-pyridyl)tetrazolyl)-pentane, 3-bptzp = 1,4-bis(5-(3-pyridyl)tetrazolyl)-butane) were synthesized and used as electrode material precursors as well. However, no HMB was produced on the surface of complexes 2 and 3 by similar electrochemical treatment. 1-HMB/CC-0.15 is taken as cathode to assemble an asymmetric supercapacitor (ASC) device, which demonstrates an ultrahigh energy density of 23.71 Wh kg−1 at the power density of 0.7 KW kg−1. After 5000 galvanostatic charge/discharge cycles, the aqueous ASC device can retain 86.8% of its capacitance, showing good cyclic stability. The effects brought by the electrochemical treatment and the structure of complexes on the pseudocapacitive behavior are discussed, respectively.

Objective To evaluate the diagnostic value of interferon-γ release assay of blood and pleural effusion for tuberculous pleurisy. Methods Fifty-six adult patients with suspected tuberculous pleurisy were enrolled in our study. The blood and pleural effusion interferon-γ release assay were measured by T-SPOT.TB test in 38 pleural tuberculosis patients and 18 non-tuberculous pleurisy controls. The diagnostic sensitivity, specificity, predictive value of T-SPOT.TB in pleural effusion mononuclear cells (PE-MC) and peripheral mononuclear cells (PBMC) were analyzed. Results The sensitivities and specificities, positive predictive values and negative predictive values, respectively, of the PE-MC and PBMC for diagnosing were as follows: 86.5%(95% confidence interval[CI] 71.2%-95.5%) and 100%(95%CI 90.5%-100%); 52.9%(95%CI 27.8%-77.0%) and 35.3%(95%CI 14.2%¬61.7%); 80.0%(95%CI 64.4%-90.9%) and 77.1%(95%CI 62.7%-88.0%); 64.3%(95%CI 35.1%-87.2%) and 100%(95%CI 54.1%¬100%). By ROC curve analysis, a cut-off value of 47SFC/2.5×105 cells in PE-MC showed a sensitivity of 89.2% and a specificity of 88.2%. Conclusion T-SPOT.TB in PE-MC could be an accurate diagnostic method for tuberculous pleurisy in TB endemic settings. Moreover, 47SFC/2.5×105 cells might be the optimal cut-off value for diagnosing tuberculous pleurisy. DOI: 10.11855/j.issn.0577-7402.2018.01.11

Heterozygous germline mutation of the MEN1 tumor suppressor gene is responsible for multiple endocrine neoplasia type 1. Parathyroid and thoracic neuroendocrine tumor specimens and DNA from two Han Chinese MEN1 family patients were analyzed using whole exome and Sanger sequencing. The proband (II-3) was sequentially diagnosed with pituitary adenoma, pancreatic tumor, adrenal cortical tumor, abdominal lipoma, and parathyroid adenoma during the 6-year follow-up. The son of the proband (III-6) was also diagnosed with a thoracic neuroendocrine tumor and a parathyroid adenoma during this period. Splice alterations were studied by RT-PCR and sequencing. The mutation impact was evaluated using bioinformatics. Sequence analysis revealed a novel splice donor mutation, MEN1 IVS9 + 1G > C, that changed the splicing mode of MEN1 to halt translation before two nuclear localization signals in the menin protein. Novel somatic mutations, MEN1 c.1402_1405delGAGG and c.286 C > T, were identified in the parathyroid adenoma of II-3 and thoracic neuroendocrine tumor of III-6, respectively, indicating a two-hit etiology of MEN1 syndrome. Our study revealed the clinical and genetic basis of MEN1 in this Han Chinese family and provides insight into MEN1 mechanisms, diagnosis, and management.

Objectives. To explore the independent associations of sedentary behavior and physical activity with telomere length among Chinese adults. Methods. Data on total time of sedentary behavior, screen-based sedentary behavior (including television watching and computer or phone use), moderate to vigorous physical activity, and dietary intake of 518 adults in Chengdu, Guizhou, and Xiamen in China (54.25% women) aged 20 to 70 years were obtained between 2013 and 2015 through questionnaires. Height, weight, and waist circumference were measured to calculate body mass index and percentage of body fat. Telomere length was measured through Southern blot technique. Results. Television watching was inversely related to adjusted telomere length (−71.75 base pair; SE = 34.40; P = .04). Furthermore, a similar trend between telomere length and television watching was found in the group aged 20 to 40 years after adjusting for all covariates. Adults aged 20 to 40 years in the highest tertile of daily time spent on watching television had 4.0% shorter telomere length than adults in the lowest tertile (P = .03). Conclusions. Although the association is modest, television watching is inversely related to telomere length among Chinese adults, warranting further investigation in large prospective studies.

Background: Colon Cancer-Associated Transcript 2 (CCAT2) has been demonstrated associated with clinical outcomes in various tumors. However, the results from each study were unfortunately insufficient and not completely consistent. Therefore, we conduct a systematic meta-analysis to evaluate the value for a feasible biomarker for metastasis and prognosis. Methods: A meta-analysis was performed using data obtained through a systematic search of PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Wanfang database and VIP database. The pooled odds ratio (OR) and hazard ratio (HR) with 95% Confidence interval (CI ) using random-effect were used to identify the relationship of CCAT2 with clinical outcome of cancer patients. Subgroup analysis and sensitivity analysis were performed. Results: A total of 867 patients from eight studies were finally included. Patients with high CCAT2 expression underwent an increased risk of lymph node metastasis (LNM) (OR=3.09, 95% CI: 1.53-6.26) and distant metastasis (DM) (OR=7.70, 95% CI: 3.26-18.17). CCAT2 was also significantly correlated with overall survival (OS) (HR=2.19, 95%CI: 1.70-2.82) and progression-free survival (PFS) (HR=2.59, 95% CI: 1.78-3.76). Moderate heterogeneity was observed in meta-analysis for LNM. However, the results remained robust in multiple sensitivity analyses. Conclusions: High expression of CCAT2 was linked with poor clinical outcome. CCAT2 can serve as a potential molecular marker for prognosis in different types of cancers.

Drought is one of the most severe environmental factors limiting plant growth and productivity. Plants respond to drought by closing stomata to reduce water loss. The molecular mechanisms underlying plant drought resistance are very complex and yet to be fully understood. While much research attention has been focused on the positive regulation of stomatal closure, less is known about its negative regulation, equally important in this reversible process. Here we show that the MADS-box transcriptional factor AGL16 acts as a negative regulator in drought resistance by regulating both stomatal density and movement. Loss-of-function mutantagl16was more resistant to drought stress with higher relative water content, which was attributed to a reduced leaf stomatal density and more sensitive stomatal closure due to a higher leaf ABA level compared with wild type, whileAGL16overexpression lines displayed the opposite phenotypes.AGL16is preferentially expressed in guard cells and down regulated in response to drought stress. The expression ofCYP707A3andAAO3in ABA metabolism andSDD1in stomatal development was altered by AGL16 as shown inagl16and overexpression lines. Chromatin immunoprecipitation, transient transactivation, and yeast-one-hybrid assays demonstrated that AGL16 bound the CArG motif in the promoter of theCYP707A3,AAO3, andSDD1to regulate their transcription, and therefore alter leaf stomatal density and ABA level. Taken together, AGL16 acts as a negative regulator of drought resistance by modulating leaf stomatal density and ABA accumulation.

Enormous technological promise of multi-walled carbon nanotubes (MWCNTs) can only be harnessed with the premise of controllable synthesis of MWCNTs, where catalyst precursor and promoter play vital roles. Herein, we have systematically investigated the effects of pre-treatment of catalyst precursor and promoter and growth conditions of MWCNTs. The highest yield of MWCNTs from thiophene-based Ni-coordination polymer is 10 times as that of our previous work. The results indicate that catalyst precursor and promoter can efficiently tune the morphology, yield and quality of MWCNTs.

Objective To investigate the epidemiology and clinical characteristics of autoimmune hepatitis (AIH). Methods Hospitalization data of 62 consenting patients with autoimmune hepatitis admitted to the First Affiliated Hospital of Ji'nan University from November 2002 to March 2014 were collected. Clinical characteristics, epidemiology, serum IgG or γ-globulin levels, liver function indices, and liver fibrosis indices in these patients were analyzed. Results ①62 patients participated in this research, including 9 males and 53 females. The male-female ratio of AIH patients was 1:5.89. The patients, age ranged from 15 to 79 years (median age 56 years), and middle aged patients accounted for 40.3% (25 patients). Fatigue (61.3%), hepatomegaly (54.8%) and loss of appetite (53.2%) were the most common clinical symptoms. Type ⅠAIH accounted for 77.42%, type Ⅱfor 3.23%, type Ⅲfor 3.23% and type Ⅳfor 16.13%. ②Different types of AIH patients showed no statistically significant difference in the gender, age, clinical manifestations and incidence of complications, serum IgG or γ-globulin levels and liver function. ③Due to the limited size of type Ⅱ, type Ⅲand type ⅣAIH patients, only type ⅠAIH patients were enrolled in a further analysis. In type ⅠAIH patients, the incidences of abdominal distension, palmar erythema, spider nevi, edema of lower extremities, upper gastrointestinal hemorrhage and spontaneous peritonitis were higher in males. Females had a higher concentration of gamma glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP), and a lower concentration of hyaluronic acid and laminin. Type ⅠAIH patients in all age groups showed no statistical ly significant difference in clinical manifestations and incidence of complications, serum IgG or γ-globulin levels and liver function. Conclusions AIH predominantly affects middle-aged women. Fatigue, hepatomegaly and reduction of appetite are the most common clinical symptoms. Type Ⅰis the most common type among the three types. Females has a higher concentration of GGT and ALP and a lower concentration of hyaluronic acid and laminin. DOI: 10.11855/j.issn.0577-7402.2016.08.13

Objective To evaluate the association between modest alcohol consumption and the risk of fatty liver disease (FLD) or nonalcoholic fatty liver disease (NAFLD). Methods PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Digital Journal Full-text Database, and database for Chinese Technical Periodicals (VIP) till Nov. 2015 were searched for the studies in evaluating the effect of alcohol consumption on FLD or NAFLD. The quality assessment of included studies was performed according to the combined evaluation for cross-sectional studies and Newcastle-Ottawa scale (NOS) for cohort studies. A meta-analysis was performed using Stata12.0 software. Results A total of 16 studies including 13 cross-sectional studies, 2 cross-sectional following longitudinal studies, and 1 cohort study with 76 967 participants were selected finally. The results of Meta-analysis were as follows. Minimal and light alcohol consumptions reduced the risk for FLD or NAFLD by 17% and 27%, respectively, and moderate alcohol consumption was marginally associated with decreased risk for FLD or NAFLD. The results of subgroup analysis by gender showed that (1) Minimal and light alcohol consumptions reduced the risk of FLD or NAFLD by 29% and 33%, respectively, but moderate alcohol consumption was not statistically significant in reducing the risk of FLD or NAFLD in females compared with controls; (2) Light alcohol consumption reduced the risk of FLD or NAFLD by 23%, but minimal and moderate alcohol consumptions were not statistically significant in reducing the risk of FLD or NAFLD in male compared with controls; (3) Light and moderate alcohol consumptions in Asian males reduced the risk of FLD or NAFLD by 29.7% and 30.3%, respectively. Conclusions Modest alcohol consumptions may not increase the risk of FLD or NAFLD. Inversely, minimal and light alcohol consumptions in female reduce the risk of FLD or NAFLD remarkably, and light to moderate alcohol consumption in males, especially in Asian males, can also significantly reduce the risk of FLD or NAFLD. DOI: 10.11855/j.issn.0577-7402.2016.07.15