Accumulated ß-catenin is associated with human atrial fibrosis and atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with increased risk of stroke and mortality. It has been reported that the process of atrial fibrosis was regulated by ß-catenin in rats with AF. However, pathophysiological mechanisms of this process in human with AF remain unclear. This study aims to investigate the possible mechanisms of ß-catenin in participating in the atrial fibrosis using human right atrial appendage (hRAA) tissues . METHODS: We compared the difference of ß-catenin expression in hRAA tissues between the patients with AF and sinus rhythm (SR). The possible function of ß-catenin in the development of AF was also explored in mice and primary cells. RESULTS: Firstly, the space between the membrane of the gap junctions of cardiomyocytes was wider in the AF group. Secondly, the expression of the gap junction function related proteins, Connexin40 and Connexin43, was decreased, while the expression of ß-catenin and its binding partner E-cadherin was increased in hRAA and cardiomyocytes of the AF group. Thirdly, ß-catenin colocalized with E-cadherin on the plasma membrane of cardiomyocytes in the SR group, while they were dissociated and accumulated intracellularly in the AF group. Furthermore, the expression of glycogen synthase kinase 3ß (GSK-3ß) and Adenomatous Polyposis Coli (APC), which participated in the degradation of ß-catenin, was decreased in hRAA tissues and cardiomyocytes of the AF group. Finally, the development of atrial fibrosis and AF were proved to be prevented after inhibiting ß-catenin expression in the AF model mice. CONCLUSIONS: Based on human atrial pathological and molecular analyses, our findings provided evidence that ß-catenin was associated with atrial fibrosis and AF progression.

Laser Writable Multifunctional van der Waals Heterostructures.

Achieving multifunctional van der Waals nanoelectronic devices on one structure is essential for the integration of 2D materials; however, it involves complex architectural designs and manufacturing processes. Herein, a facile, fast, and versatile laser direct write micro/nanoprocessing to fabricate diode, NPN (PNP) bipolar junction transistor (BJT) simultaneously based on a pre-fabricated black phosphorus/molybdenum disulfide heterostructure is demonstrated. The PN junctions exhibit good diode rectification behavior. Due to different carrier concentrations of BP and MoS2 , the NPN BJT, with a narrower base width, renders better performance than the PNP BJT. Furthermore, the current gain can be modulated efficiently through laser writing tunable base width WB , which is consistent with the theoretical results. The maximum gain for NPN and PNP is found to be ≈41 (@WB ≈600 nm) and ≈12 (@WB ≈600 nm), respectively. In addition, this laser write processing technique also can be utilized to realize multifunctional WSe2 /MoS2 heterostructure device. The current work demonstrates a novel, cost-effective, and universal method to fabricate multifunctional nanoelectronic devices. The proposed approach exhibits promise for large-scale integrated circuits based on 2D heterostructures.

[Neural mechanisms of visual selective attention].

Because of a limited capacity of information processing in the brain, the efficient processing of visual information requires selecting only a very small fraction of visual inputs at any given moment in time. Attention is the main mechanism that controls this selection process, namely selective attention. Selective attention is the mechanism by which the subset of incoming information is preferentially processed from the complex external environment. Research on selective attention has two key issues. One is what targets (inputs) are selected by attention. There are three different types of selective attention according to its selected target: space-based, feature-based, and object-based attention. Another issue is how selective attention is generated. There are two different types of selective attention according to its generating source: top-down and bottom-up attention. In this review, these two issues are introduced to systematically discuss the neural mechanism of visual selective attention.

Whole-Exome Sequencing and Experimental Validation Unveil the Roles of TMEM229A Q200del Mutation in Lung Adenocarcinoma.

INTRODUCTION: Lung adenocarcinoma (LUAD) is one of the major histopathological types of non-small cell lung cancer (NSCLC), including solid, acinar, lepidic, papillary and micropapillary subtypes. Increasing evidence has shown that micropapillary LUAD is positively associated with a higher percentage of driver gene mutations, a higher incidence of metastasis and a poorer prognosis, while lepidic LUAD has a relatively better prognosis. However, the novel genetic change and its underlying mechanism in the progression of micropapillary LUAD have not been exactly determined. METHODS: A total of 181 patients with LUAD who underwent surgery at the First Affiliated Hospital of Huzhou University from January 2020 to December 2022 were enrolled. Three predominant lepidic and three predominant micropapillary LUAD tissue samples were carried out using whole-exome sequencing. Comprehensive analysis of genomic variations and the difference between lepidic and micropapillary LUAD was performed. In addition, the TMEM229A Q200del mutation was verified using our cohort and TCGA-LUAD datasets. The correlations between the TMEM229A Q200del mutation and the clinicopathological characteristics of patients with LUAD were further analyzed. The functions and mechanisms of TMEM229A Q200del on NSCLC cell proliferation and migration were also determined. RESULTS: The frequency of genomic changes in patients with micropapillary LUAD was higher than that in patients with lepidic LUAD. Mutations in EGFR, ATXN2, C14orf180, MUC12, NOTCH1, and PKD1L2 were concomitantly detected in three predominant micropapillary and three predominant lepidic LUAD cases. The TMEM229A Q200del mutation was only mutated in lepidic LUAD. Additionally, the TMEM229A Q200del mutation had occurred in 16 (8.8%) patients, and not found TMEM229A R76H and M346T mutations in our cohort, while TMEM229A mutations (R76H, M346T, and Q200del) occurred only in 1.0% of the TCGA-LUAD cohort. Further correlation analysis between the TMEM229A Q200del mutation and clinicopathological characteristics suggested that a lower frequency of the Q200del mutation was significantly associated with positive lymph node metastasis, advanced TNM stage, positive cancer thrombus, and pathological features. Finally, overexpression of TMEM229A Q200del suppressed NSCLC cell proliferation and migration in vitro. Mechanistically, overexpression of TMEM229A and TMEM229A Q200del both reduced the expression level of phosphorylated (p)-ERK and p-AKT (Ser473), and the reduced protein level of p-ERK in the TMEM229A Q200del group was more pronounced compared to the TMEM229A group. CONCLUSION: Our results demonstrated that the TMEM229A Q200del mutant may play a protective role in the progression of LUAD via inactivating ERK pathway, providing a potential therapeutic target in LUAD.

Alkaloids isolated from the endophytic fungus Fusarium concentricum.

Endophytic fungi are an important resource for bioactive natural products. In this study, a new tryptophan derivative fusaconate A (1) and three pyridone alkaloids, including one new pyridone derivative 1'-methoxy-6'-epi-oxysporidinone (2) and two known ones (3-4), were identified from the endophytic fungus Fusarium concentricum which was isolated from the medicinal plant Anoectochilus roxburghii. Their structures were elucidated through extensive spectroscopic analysis, including HR-ESI-MS, 1 D and 2 D NMR. Compound 4 exhibited moderate cytotoxicities against HT29 and PC3 cells with IC50 values of 7.60 and 4.99 µM, respectively.

Prevalence, incidence and mortality of hypertrophic cardiomyopathy based on a population cohort of 21.9 million in China.

There are limited studies on the prevalence and incidence of clinically diagnosed hypertrophic myocardiopathy (HCM) and its mortality in the Chinese population, and the projected population burden of HCM over the next decades. We collected data on HCM and its mortality from the Beijing Municipal Health Commission Information Center (BMHCIC) database and estimated the prevalence and incidence based on the whole Beijing population. Calculation of population trends was performed using annual percentage change (APC) and average annual percentage change (AAPC). Finally, future HCM incidence was built by modelling projection of HCM to the next decades using Poisson regression analysis and Gray Model 1,1(GM [1,1]). The prevalence of HCM was 0.0069% (95%CI, 0.0065-0.0072%; N = 1343) in 2010, rising to 0.076% (95% CI, 0.074-0.077%; N = 16,616) in 2019, and the incidence of HCM was 6.85 per 100 000 person-year in 2010, rising to 11.76 per 100 000 person-year in 2019. Males had higher prevalence and incidence of HCM than females. The APPC for the rising incidence of HCM was 5.8% and the expected numbers will double increase in 2029 by assuming the same increase trend as the last decades. HCM had increased annual incidence of HF (APPC: 8.4, 4.4-12.6, p < 0.05), and relatively stable annual incidence of mortality (APPC: 1.2%, - 2.3% to 4.8%, p > 0.05) during the studied period. Males had lower mortality (2.70% vs. 4.20%, p < 0.001) than females. The calculated HCM prevalence was much lower compared to prior screening studies from 2004, although the predicted HCM incidence would double over the next decades. HCM was associated with a stable risk of mortality during the studied period.

PPDPF promotes lung adenocarcinoma progression via inhibiting apoptosis and NK cell-mediated cytotoxicity through STAT3.

Lung cancer is the most common malignancy and the leading cause of cancer death worldwide, and lung adenocarcinoma (LUAD) is the most prevalent subtype. Considering the emergence of resistance to therapies, it is urgent to develop more effective therapies to improve the prognosis. Here we reported that pancreatic progenitor cell differentiation and proliferation factor (PPDPF) deficiency inhibited LUAD development both in vitro and in vivo. Mechanistically, PPDPF induces hyperactive STAT3 by interfering STAT3-PTPN1 interaction. Activated STAT3 promoted BMPR2 transcription, which further inhibited apoptosis. Moreover, PPDPF reduced NK cell infiltration and activation to develop an immunosuppressive microenvironment, which was also mediated by STAT3. Furthermore, we identified that the expression of PPDPF was positively correlated with the malignant features of LUAD, as well as BMPR2 and p-STAT3 level in clinical samples. Therefore, our study suggests that PPDPF positively regulates BMPR2 expression and facilitates immune escape via regulating STAT3 activity, providing a potential therapy target for LUAD.

[Fluorescence spectroscopic characteristics of fulvic acid from the long-term located fertilization in black soil].

In order to investigate the effect of long-term located fertilization on soil fulvic acid (FA), in this study, four soil samples were taken from black soil with long-term located fertilization (about 30 year) in Harbin, Heilongjiang province. The fertilization treatments included control (CK), N, P and K fertilization (NPK), horse manure (OM), combination of organic manure and chemical fertilizations (MNPK). Soil FA was extracted from the samples and purified. The excitation, emission, synchronous, and three-dimensional-excitation emission matrix fluorescence spectroscopy (3DEEM) characteristics of the FA were determined. The excitation, emission and synchronous scan spectra all indicated that the main peaks of FA in the NPK treatment exhibited a significantly blue shift compared with CK, while those of MNPK, OM treatment caused a red shift to some extent. 3DEEM spectra of FA in all treatments exhibited four peaks (peak a, peak b, peak c, and peak d), compared with FA in CK, the wavelengths shift tendency of peak a, peak b, and peak c of FA 3DEEM in NPK, MNPK and OM treatments were similar to that of traditional spectra in FA. In order to provide quantitative information of FA humification degree in different treatments, we investigated the fluorescence index f450/500 (FI), area integration (A370-600 nm, A1 370-412 nm, A4 538-600 nm). Compared with CK, the f450/500, ratio of A1/A in NPK and A4/A in MNPK treatment increased by 4.62%, 6.12%, 7.22%, respectively. However, the f450/500, the ratio of A1/A in MNPK and A4/A in NPK treatment decreased by 3.86%, 15.31%, and 7.22% respectively. This indicated that NPK application gave a lower degree of FA humification, and combination of organic manure and chemical fertilizations would lead to a greater degree of FA aromatization in black soil with long-term located fertilization than CK.

Risk of prevalence of latent tuberculosis infection in health care workers-an idiographic meta-analysis from a Chinese perspective.

BACKGROUND: China is one of the countries sharing the major burden of tuberculosis (TB) in the world. Health care workers (HCWs) are subject to a high risk of occupational latent tuberculosis infection (LTBI)-an asymptomatic state of TB disease. However, the heterogenic composition of healthcare professionals in terms of nature of their work leads to the inconsistency in predicting the prevalence of LTBI amongst them. Furthermore, the global statistics do not account for the analysis conducted within the Chinese population. Our study reflects a systemic and epidemiological meta-analysis to investigate the risk of contracting LTBI by the HCWs of China. METHODS: A systematic review of the literature was performed to identify studies reporting LTBI prevalence or incidence among HCWs and a control groups in China. Risk of infection, as well as subgroup analysis was calculated by pooled effect estimates. Review Manager 5.0 was used to perform the meta-analyses. RESULTS: Twenty studies containing 9,654 HCWs met the inclusion criteria. The average prevalence of LTBI among HCWs was 51.5%, ranging from 27.9-88.8%. HCWs had a higher risk of prevalence of LTBI than the control groups [odds ratio (OR), 1.78, 95% confidence interval (CI), 1.46-2.16]. In the subgroup analysis, the prevalence of LTBI in HCWs with respect to the control groups was observed to be highest in Eastern China (OR, 2.05; 95% CI, 1.35-3.11). Furthermore, the pooled OR for LTBI was 1.90 and 1.65 separately from the results of the tuberculin skin test (TST) and the interferon-gamma release assay. Lastly, upon comparing the HCWs with the control groups from the community and the nosocomial source, it was observed that the pooled OR favored for the prevalence of LTBI, which was primarily community-sourced (3.12 and 1.54). HCWs had an increased risk of prevalence of LTBI than the control groups, both in general hospitals and TB specific hospitals (pooled OR 2.4 and 1.57). CONCLUSIONS: Risk of LTBI infection among HCWs is relatively high in China, especially in the eastern region, predisposed by the cumulative exposure to Mycobacterium tuberculosis from the community and the general hospitals. Overall, our data reflects an alarming risk posed to our HCWs, and calls for immediate reforms at the policy levels, so as to implement effective screening and treatment of affected HCWs in China.

Layer contribution to optical signals of van der Waals heterostructures.

The optical signals (such as Raman scattering, absorption, reflection) of van der Waals heterostructures (vdWHs) are very important for structural analysis and the application of optoelectronic devices. However, there is still a lack of research on the effect of each layer of two-dimensional materials on the optical signals of vdWHs. Here, we investigated the contribution from different layers to the optical signal of vdWHs by using angle-resolved polarized Raman spectroscopy (ARPRS) and angle-dependent reflection spectroscopy. A suitable theoretical model for the optical signal of vdWHs generated by different layers was developed, and vdWHs stacked by different two-dimensional (2D) materials were analyzed. The results revealed a strong dependence of the relative strengths of the optical signals of the upper and lower layers on the thicknesses of 2D materials and the SiO2 layer on the Si/SiO2 substrate. Interestingly, on the 285 nm SiO2/Si substrate, the contribution to the optical signal by the underlying 2D material was much greater than that by the upper layer. Furthermore, optical signals originating from different layers of twisted black phosphorus (BP) for different twist angles were studied. There is great significance for optical spectroscopy to study vdWHs, as well as the development of better twisted 2D materials and moiré physics.

A gate-tunable symmetric bipolar junction transistor fabricated via femtosecond laser processing.

Two-dimensional (2D) bipolar junction transistors (BJTs) with van der Waals heterostructures play an important role in the development of future nanoelectronics. Herein, a convenient method is introduced for fabricating a symmetric bipolar junction transistor (SBJT), constructed from black phosphorus and MoS2, with femtosecond laser processing. This SBJT exhibits good bidirectional current amplification owing to its symmetric structure. We placed a top gate on one side of the SBJT to change the difference in the major carrier concentration between the emitter and collector in order to further investigate the effects of electrostatic doping on the device performance. The SBJT can also act as a gate-tunable phototransistor with good photodetectivity and photocurrent gain of ß = ∼21. Scanning photocurrent images were used to determine the mechanism governing photocurrent amplification in the phototransistor. These results promote the development of the applications of multifunctional nanoelectronics based on 2D materials.

Involvement of prophenoloxidases in the suppression of Plasmodium yoelii development by Anopheles dirus.

Anopheles dirus is refractory to a rodent malaria parasite, Plasmodium yoelii, and melanized oocysts are manifested in infected mosquitoes. Prophenoloxidase (PPO) is a zymogen whose active form mediates melanotic encapsulation of invading pathogens in mosquitoes. In this study, we cloned cDNA fragments of four An. dirus PPOs, that are orthologs of Anopheles gambiae PPO2, PPO4, PPO5 and PPO6. AdPPO4 expression in hemocytes was induced in response to P. yoelii infection. RNA interference using double stranded RNA of AdPPO4 led to depletion of its mRNA and other PPO transcripts. This depletion increased P. yoelii infection prevalence and oocyst intensity, and abolished the melanization of oocysts as well. Therefore, An. dirus PPOs may play a role in the refractoriness to P. yoelii.

[Innate immune defense in anopheline mosquitoes against plasmodium infection].

On the basis of the research on interaction between plasmodium and mosquito vector, the mechanism of innate immune defense responses in anopheline mosquitoes against plasmodium infection has been studied. The innate immune defense may be applied to confine and kill malaria parasites under migration and development, to an effective control strategy on malaria vectors.

[Study on the relationship between intracellular free calcium and melanization in oocysts of Plasmodium yoelii].

OBJECTIVE: To study the change of intracellular free Ca2+ in the oocyst when it melanized and to find out the relationship between the melanized oocyst and its intracellular level of free Ca2+ in a Plasmodium-refractory strain of Anopheles dirus. METHODS: The distribution and experimental condition of the intracellular free Ca2+ in oocyst of Plasmodium yoelii was measured with Ca2+ sensitive dye Fluo-3/AM and Pluronic F-127 under confocal laser scanning microscope (CLSM) at different time. RESULTS: The best load condition was that the oocysts were incubated in 3 mumol/ml Fluo-3/AM adding 1 microliter/ml 25% Pluronic F-127 for 60 min at 37 degrees C. Fluorescent imaging of oocysts was affected by an increase or decrease of the concentration of Fluo-3/Am and incubation time. The distribution of intracellular free Ca2+ was heterogeneous in the oocysts. The mean value of Ca2+ in the mature oocysts was (137.15 +/- 7.02) nmol/L (X +/- S) but was (18.44 +/- 1.75) nmol/L in melanized oocysts with Ca2+ sedimentation in the wall of oocyst. CONCLUSION: The results suggest that the level of the intracellular free Ca2+ in oocyst decreased and excreted during its melanization in a Plasmodium-refractory anopheline mosquito species.

[cDNA cloning and location of Pagumogonimus skrj abini cysteine protease].

OBJECTIVE: To clone the cysteine protease cDNA fragment from Pagumogonimus skrjabini adults and locate the tissue of the adult worm where cysteine protease is expressed. METHODS: The cysteine protease cDNA fragment was amplified by reverse transcription-polymerase chain reaction (RT-PCR) with degenerated primers. The production was TA-cloned into the pUCm-T vector and sequenced. DNASIS program was used to analyse the nucleotide sequence and deduce the amino acid sequence, which was aligned with the correlated parasite cysteine protease afterwards. The digoxin labeled cRNA probe was synthesised by in vitro transcription with the cloned cDNA as template. The frozen sections of the adult worms were analysed by hybridization in situ to locate the gene expression. RESULTS: A 495 bp cDNA fragment was amplified by RT-PCR and sequenced. An amino acid sequence was deduced by DNASIS. Sequence analysis and alignment showed significant homologies with the correlated parasite cysteine proteinases and conservation of Cys, His and Asn residues that from a catalytic triad. In the hybridization in situ analysis, intestinal epithelium was stained positively on transverse section of adult worms. CONCLUSION: The cysteine proteinase cDNA fragment from Pagumogonimus skrjabini adults was cloned. There are some key sites which are correlated to the function of cysteine protease in the cDNA fragment. Cysteine protease is mainly expressed in intestinal epithelium of P. skrjabini.

[Endemic situation and control strategies on schistosomiasis in Armed Police Forces in marshland and lake regions].

OBJECTIVE: To investigate the prevalence of schistosomiasis in Armed Police Forces in marshland and lake regions so as to provide the evidence for policy-making of the disease control. METHODS: The different types of duty were selected by the stratified cluster random sampling method in endemic areas of marshland and lake regions, and the snail survey was conducted, and the infectious status and epidemic factors of officers and soldiers who served more than 2 years were investigated. RESULTS: The geographical features included the embankment type, island type and islet type, and the serological positive rates were 1.88%, 4.73% and 3.89% in the 3 types of endemic areas respectively and he total positive rate was 3.10%, that was lower than the national population level in 2009. The infection risk factors included fighting flood, and the contact with infested water in daily life and production. CONCLUSIONS: We should strengthen the surveillance and control of schistosomiasis in this particular group of officers and soldiers, especially in their implementation of fighting flood and other tasks.

Distribution and clinical features of Paragonimiasis skrjabini in Three Gorges Reservoir Region.

Paragonimiasis has previously been reported in the Southwest Provinces of China, including Chongqing and Sichuan. The construction of Three Gorges Dam, which was begun in 1994, has resulted in substantial changes to the depth and the flow pattern of the Yangtze River. To investigate epidemiology of the paragonimiasis, 724 people aged 2-49 years were selected and examined for Paragonimus infection by intradermal test (IDT), and enzyme-linked immunosorbent assay (ELISA). A survey of eating habits was conducted face-to-face in 5 endemic counties. Freshwater crabs were collected from seven sites in the 5 counties to determine the rate of infection with Paragonimus metacercariae. Additionally, we analyzed 213 case reports from the region dated 2006 to 2009. According to the survey results, the prevalence of Paragonimus skrjabini infection in freshwater crab was 39.65%, and the human infection rates detected by IDT and ELISA were 14.36% (104/724) and 7.46% (54/724), respectively. These results show that the Three Gorges Reservoir is still an area of high paragonimiasis endemicity. The water level of the Yangtze River has risen to 175 m, and the area of water coverage in the region has increased to 1084 km(2). These conditions will favor the growth and expansion of the freshwater crab population.