[Evaluation of the efficacy of urine-based lipoarabinomannan antigen test in the diagnosis of pulmonary tuberculosis].

Objective: To analyze the diagnostic efficacy of urinary lipoarabinomannan (LAM) antigen detection method in tuberculosis patients, and to provide an experimental basis for the clinical application of urinary LAM kit in China. Methods: From March to May 2023, 228 patients with lung diseases [134 male, 94 female, age 20-82 (44.8±16.7) years] were prospectively collected in Beijing Chest Hospital, Capital Medical University, including 143 pulmonary tuberculosis patients and 85 non-tuberculosis patients. Urine and sputum samples from patients were collected for traditional etiological detection and urinary LAM antigen detection. The screening results of each positive detection combination were analyzed, and the difference analysis and regression analysis were performed. Results: The detection sensitivity and specificity of the urinary LAM kit were 46.2% (95%CI: 37.9%-54.7%) and 96.5% (95%CI: 89.3%-99.1%), respectively, with an overall coincidence rate of 64.9%. The detection rate of LAM antigen detection and GeneXpert MTB/RIF (Xpert) combined (60.8%, 87/143) was significantly higher than that of Xpert alone (49.7%, 71/143), and the difference was statistically significant (P<0.05). The results of risk factor analysis showed that the risk of negative urinary LAM antigen test results increased significantly as the bacterial load decreased. Conclusions: Urine LAM antigen detection method has a high specificity and can be combined with traditional methods to effectively improve the detection rate. Urinary LAM antigen detection method still has limitations, such as the influence of bacterial load and the inability to distinguish nontuberculosis mycobacteria samples, which needs further experimental verification.

Molecular mechanisms of MCM3AP-AS1 targeted the regulation of miR-708-5p on cell proliferation and apoptosis in gastric cancer cells.

The article "Molecular mechanisms of MCM3AP-AS1 targeted the regulation of miR-708-5p on cell proliferation and apoptosis in gastric cancer cells, by H. Wang, T. Xu, L. Wu, H.-L. Xu, R.-M. Liu, published in Eur Rev Med Pharmacol Sci 2020; 24 (5): 2452-2461-DOI: 10.26355/eurrev_202003_20512-PMID: 32196596" has been withdrawn from the authors due to the discovery of new results. The authors decided to improve them further. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20512.

Phase transitions in the classical exchange-anisotropic Kitaev-Heisenberg model.

The Kitaev model on the honeycomb lattice has been receiving substantial attention due to the discovery of quantum spin liquid state associated with this model. Consequently, its classical partners such as the Kitaev-Heisenberg (KH) model and associated phase transitions become concerned. Specifically, an intermediate Kosterlitz-Thouless (KT) phase engaged in the transition from the high-temperature (T) disordered state to the low-T sixfold degenerate state is predicted in the isotropic KH model [Phys. Rev. Lett. 109, 187201 (2012)10.1103/PhysRevLett.109.187201], but so far no sufficient experimental proof has been reported. In this work, we consider an essential extension of this KH model on the honeycomb lattice by including the Kitaev exchange anisotropy that is non-negligible in realistic materials. The associated phase transitions are thus investigated using the Monte Carlo simulations. It is found that such an anisotropy will result in a degradation of the sixfold degeneracy of the ground state in the isotropic KH model down to the fourfold or twofold degenerate ground state, and the finite-T phase transitions will also be modified remarkably. Interestingly, the intermediate KT phase can be suppressed by this Kitaev exchange anisotropy. This work thus provides a more realistic description of the physics ingredient with the KH model and presents a possible explanation on absence of the intermediate phase in real materials where the Kitaev exchange anisotropy can be more or less available.

Molecular mechanisms of MCM3AP-AS1 targeted the regulation of miR-708-5p on cell proliferation and apoptosis in gastric cancer cells.

OBJECTIVE: Gastric cancer (GC) is a common malignancy of the digestive tract. Accumulated studies proved that long non-coding RNA MCM3AP-AS1 (MCM3AP-AS1) modified the mechanism of the progression of GC. However, the molecular mechanism is still greater elusive. Hence, we aimed to explore the molecular mechanism of MCM3AP-AS1 targeting the regulation of microRNA-708-5p on cell proliferation and apoptosis in GC cells. MATERIALS AND METHODS: The expression levels of MCM3AP-AS1 (MCM3AP antisense RNA 1) in gastric mucosal cells GES-1 and gastric cancer cell lines of MGc-803 and SGC-7901 cells were detected by qRT-PCR. Moreover, the protein levels of Cyclin D1, P21, Bax and Bcl-2 in MGc-803 and SGC-7901 cells after transfection were detected by Western blot. MTT assay was performed to detect cell proliferation and flow cytometry was carried out to determine GC cell apoptosis in vitro. In the endpoint, the targeting relationship between MCM3AP-AS1 and microRNA-708-5p was detected by Dual-Luciferase reporter assay. RESULTS: The level of MCM3AP-AS1 was significantly promoted in GC cell lines. Knockdown of MCM3AP-AS1 curbed cell proliferation and enhanced apoptosis in MGc-803 and SGC-7901 cells. Furthermore, the effect of the downregulation of MCM3AP-AS1 on cell proliferation and apoptosis was reversed by knockdown of miR-708-5p, which was targeted by MCM3AP-AS1 in vitro. CONCLUSIONS: MCM3AP-AS1 regulates the proliferation and apoptosis of gastric cancer cells by targeting the expression of microRNA-708-5p. The study may be useful to the therapy target of human GC.

Synthetic chimeric nucleases function for efficient genome editing.

CRISPR-Cas systems have revolutionized genome editing across a broad range of biotechnological endeavors. Many CRISPR-Cas nucleases have been identified and engineered for improved capabilities. Given the modular structure of such enzymes, we hypothesized that engineering chimeric sequences would generate non-natural variants that span the kinetic parameter landscape, and thus provide for the rapid selection of nucleases fit for a particular editing system. Here, we design a chimeric Cas12a-type library with approximately 560 synthetic chimeras, and select several functional variants. We demonstrate that certain nuclease domains can be recombined across distantly related nuclease templates to produce variants that function in bacteria, yeast, and human cell lines. We further characterize selected chimeric nucleases and find that they have different protospacer adjacent motif (PAM) preferences and the M44 chimera has higher specificity relative to wild-type (WT) sequences. This demonstration opens up the possibility of generating nuclease sequences with implications across biotechnology.

[Tolvaptan attenuates atrial remodeling in rats undergoing chronic intermittent hypoxia via miRNA-21].

Objective: To investigate the effects and potential mechanisms of tolvaptan on chronic intermittent hypoxia (CIH)-induced atrial remodeling in rats. Methods: A total of 45 Sprague-Dawley rats were divided into 3 groups by the random number table: control group, CIH group (6 h/d for 30 days), CIH plus tolvaptan group (8 mg·kg(-1)·d(-1) per gavage for 30 days). Echocardiography examination was performed after 30 days. Thereafter, 5 rats were randomly chosen for histology evaluation, 5 for molecular biological examinations and another 5 rats underwent isolated heart electrophysiology study in each group. Protein and mRNA expression levels of miRNA-21, Spry1, PTEN, ERK/p-ERK, MMP-9, PI3K, AKT/p-AKT were detected. Results: Compared to the rats in control group, rats in the CIH group showed higher atrial interstitial collagen deposition (P<0.001), increased atrial fibrillation inducibility (P=0.022). The results of immunohistochemistry staining showed that the mean optical density (MOD) of ERK, p-ERK and MMP-9 were significantly increased (all P<0.05), the MOD of Spry1 and PTEN were significantly decreased (both P<0.05), above changes could be significantly reversed by cotreatment with tolvaptan. No significant differences were detected in PI3K and AKT among the three groups (P>0.05). In addition, compared with rats in control group, mRNA levels of miRNA-21, MMP-9, PI3K, AKT, and protein levels of ERK, p-ERK, MMP-9 were significantly increased in CIH group(all P<0.05), whereas protein levels of Spry1, PI3K, p-AKT were significantly decreased (all P<0.05). Above changes could be significantly attenuated. Conclusions: CIH induces significant atrial remodeling in this rat model, which can be attenuated by tolvaptan possibly through modulating miRNA-21/Spry1/ERK/MMP-9 and miRNA-21/PTEN/PI3K/AKT signaling pathways.

Magnetic impurity doping induced spin-glass state and short-range zigzag order in the honeycomb iridate Na2IrO3.

Based on the modified Heisenberg-Kitaev model, the effects of magnetic substitution on the magnetic properties of the honeycomb-lattice iridate [Formula: see text] [Formula: see text] are studied using Monte Carlo simulations. It is observed that the long-range zigzag state of the original system is rather fragile and can be replaced by a spin-glass state even for small substitution, well consistent with the experimental observation in Ru-substituted samples (Mehlawat et al 2015 Phys. Rev. B 92 134412). Both the disordered Heisenberg and Kitaev interactions caused by the magnetic ion-doping are suggested to be responsible for the magnetic phase transitions in the system. More interestingly, a short-range zigzag order is suggested to survive above the freezing temperature even at high magnetic impurity doping levels.

Ashkin-Teller criticality and weak first-order behavior of the phase transition to a fourfold degenerate state in two-dimensional frustrated Ising antiferromagnets.

We study the thermal phase transition of the fourfold degenerate phases (the plaquette and single-stripe states) in the two-dimensional frustrated Ising model on the Shastry-Sutherland lattice using Monte Carlo simulations. The critical Ashkin-Teller-like behavior is identified both in the plaquette phase region and the single-stripe phase region. The four-state Potts critical end points differentiating the continuous transitions from the first-order ones are estimated based on finite-size-scaling analyses. Furthermore, a similar behavior of the transition to the fourfold single-stripe phase is also observed in the anisotropic triangular Ising model. Thus, this work clearly demonstrates that the transitions to the fourfold degenerate states of two-dimensional Ising antiferromagnets exhibit similar transition behavior.

[Chronic hypoxia increases intracellular Ca(2+) concentration and augments proliferation by enhancing store-operated Ca(2+) entry in pulmonary arterial smooth muscle cells].

OBJECTIVE: To determine whether store-operated Ca(2+) entry (SOCE) is involved in chronic hypoxia-induced alteration of intracellular Ca(2+) concentration ([Ca(2+) ]i) and proliferation in pulmonary arterial smooth muscle cells (PASMC). METHODS: Rat PASMCs were cultured and treated in normoxia (21%O2) or hypoxia (4%O2) condition. The proliferation of PASMC was detected by cell counting kit-8 (CCK-8) assay. [Ca(2+) ]i, SOCE and the effects of store-operated Ca(2+) channel (SOCC) inhibitors, SKF96365 and NiCl2, on SOCE in hypoxic PASMCs were tested by InCyte [Ca(2+) ]i measurement system. RESULTS: Hypoxia for 24-60 h augmented PASMC proliferation (1.12±0.09 vs 0.71±0.05, P<0.05) and [Ca(2+) ]i [(214.8 ± 20.4) nmol/L vs (115.2±13.2) nmol/L, P<0.05] in a time-dependent manner with the maximum effect at 60 h. Perfusion of Ca(2+) -free Krebs solution containing nifedipine (5 µmol/L), cyclopiazonic acid (CPA, 10 µmol/L) in PASMCs caused a small transient increase of [Ca(2+) ]i with peak [Ca(2+) ]i (113.3±49.3) nmol/L.Chronic hypoxia (4% O2, 60 h) enhanced [Ca(2+) ]i level with peak value of (193.2±22.7) nmol/L (P<0.05) in PASMC.After restoration of extracellular Ca(2+) , CPA caused marked increase of [Ca(2+) ]i with peak value of (328.0 ±56.7) nmol/L.Chronic hypoxia strengthened CPA-induced increase of [Ca(2+) ]i with peak value of (526.0±33.7) nmol/L (P<0.05) in PASMCs.Either SKF96365 50 µmol/L or NiCl2 500 µmol/L distinctly attenuated CPA-induced enhancement of [Ca(2+) ]i, the peak value of which dropped from (526.0±33.7) nmol/L to (170.4±26.4) nmol/L (P<0.05) or (177.4±45.9) nmol/L (P<0.05) respectively. CONCLUSION: Chronic hypoxia boosts the release of Ca(2+) from sarcoplasmic reticulum and promotes the activity of SOCC and SOCE, leading to [Ca(2+) ]i elevation and proliferation of rat PASMCs.

Isolation and characterization of atrazine-degrading strain Shewanella sp. YJY4 from cornfield soil.

UNLABELLED: Atrazine has been used worldwide for over 50 years as a chemical herbicide. A strain of bacteria, YJY4 which utilizes atrazine as its sole nitrogen source for growth was isolated from agricultural black soil in northeastern China. 16S rDNA sequencing identified YJY4 as a Shewanella sp. PCR analysis and sequencing confirmed that YJY4 contained atrazine-degrading atzA, atzB and atzC genes. These genes revealed high similarity with those in Pseudomonas sp. ADP and Arthrobacter sp. TC1. The strain YJY4 was observed to degrade atrazine (100 mg l(-1) ) to cyanuric acid completely after 36 h. To the best of our knowledge, YJY4 was the first reported Shewanella sp. to grow in pure culture with atrazine serving as a sole source of nitrogen. Therefore, YJY4 may help with atrazine biodegradation and may become an abundant resource of atrazine degradation strains. SIGNIFICANCE AND IMPACT OF STUDY: A new isolated strain, YJY4 showed high atrazine-degrading ability, being able to degrade 100 mg l(-1) atrazine completely in 36 h. Strain YJY4 was identified as Shewanella sp. and contained atrazine-degrading atzA, atzB and atzC genes. This study examined the degradation mechanism and metabolic ability of this strain and for the bioremediation of contaminated environments, provides more strain selection and determines the strain of atrazine bioremediation potential.

Role of further-neighbor interactions in modulating the critical behavior of the Ising model with frustration.

In this work, we investigate the phase transitions and critical behaviors of the frustrated J(1)-J(2)-J(3) Ising model on the square lattice using Monte Carlo simulations, and particular attention goes to the effect of the second-next-nearest-neighbor interaction J(3) on the phase transition from a disordered state to the single stripe antiferromagnetic state. A continuous Ashkin-Teller-like transition behavior in a certain range of J(3) is identified, while the four-state Potts-critical end point [J(3)/J(1)](C) is estimated based on the analytic method reported in earlier work [Jin, Sen, and Sandvik, Phys. Rev. Lett. 108, 045702 (2012)]. It is suggested that the interaction J(3) can tune the transition temperature and in turn modulate the critical behaviors of the frustrated model. Furthermore, it is revealed that an antiferromagnetic J(3) can stabilize the staggered dimer state via a phase transition of strong first-order character.

Comparison of effects of devascularization versus shunt on patients with portal hypertension: a meta-analysis.

OBJECTIVE: To systematically evaluate the effectiveness of devascularization and shunt on patients with portal hypertension. METHODS: Relevant studies compared devascularization and shunt for the treatment of portal hypertension were identified searching the PubMed, Embase, Elsevier, CNKI (China National Knowledge Infrastructure) database and Cochrane Trial Register searches until December 2013. Data of interest for devascularization and shunt including postoperative recurrent bleeding, postoperative hepatic encephalopathy,ascites, operative mortality rate, and long term survival rate were subjected to meta-analysis. RESULTS: Eleven studies were included in the study, the results of the meta-analysis showed that all eleven clinical studies demonstrated a significantly higher postoperative recurrent bleeding rate with devascularization group than with shunt group (Odds Ratio =2.14, 95% CI =(1.42, 3.21), P = 0.0003),the rate of hepatic encephalopathy in the devascularization group was significantly lower compared with the shunt group (Odds Ratio =0.56, 95% CI =(0.38, 0.82), P = 0.003); Our meta-analysis of three clinical studies revealed that the reduction of ascites in the devascularization group was significantly less than the shunt groups (Odds Ratio =0.48, 95% CI =(0.26, 0.89), P = 0.02), the operative mortality rate was not significantly different between the devascularization group than for shunt group (Odds Ratio =1.54, 95% CI = (0.91,2.63), P = 0.11). And the long-term survival rate was not significantly different between the devascularization and shunt groups (Odds=1.13, ratio, 95% CI =(0.64, 1.99), P = 0.68). CONCLUSIONS: Devascularization and shunt have different advantages and disadvantages respectively which reflected in postoperative complications and long term survival rate.

Inadequate values from an interferon-gamma release assay for smear-negative tuberculosis in a high-burden setting.

OBJECTIVE: To examine the usefulness of an interferon-gamma release assay (IGRA) for the diagnosis of smear-negative tuberculosis (TB) in China. DESIGN: A total of 624 patients with presumed pulmonary TB were enrolled prospectively and categorised as smear-negative TB, smear-positive TB or no TB. All patients were tested using T-SPOT.TB. RESULTS: Both the smear-negative and smear-positive TB groups had significantly more spot-forming cells (SFCs) than the no TB group (all P < 0.001), while the smear-negative group had fewer SFCs than the smear-positive TB group (P < 0.001). The specificity of T-SPOT.TB was 60.4% (95%CI 53.4-67.1). The sensitivities of T-SPOT.TB in the smear-negative and smear-positive TB groups were respectively 81.4% (95%CI 75.7-86.0) and 93.2% (95%CI 87.6-96.4). The sensitivity in the smear-negative TB group was much lower than that in the smear-positive TB (P < 0.05). CONCLUSIONS: The sensitivity of T-SPOT.TB was lower due the paucibacillary nature of the samples, and the specificity was lower due to the high prevalence of latent tuberculous infection in the smear-negative TB patients. The T-SPOT.TB test should only be used as a supplementary test and not as a single test to rule in or rule out smear-negative TB.

Transfer of Ser7 phosphorylated CENP-A from centromere to midbody during mitosis in MCF-7 cells.

Serine 7 of centromere protein A (CENP-A) is a very important mitosis-specific phosphorylation site. In this study, we demonstrate the subcellular distribution of Ser7 phosphorylated CENP-A during mitosis in MCF-7 cells. The Ser7 phosphorylation of CENP-A was observed beginning at prophase at centromeres. Upon progression of mitosis, the fluorescence signals emerged in the central region of the metaphase plate and were maintained until anaphase at centromeres. At late anaphase, the fluorescence signals moved to the midzone gradually and transferred from the centromere to the midbody completely at telophase. They were compacted into the centre of the midbody in a thin cylinder consisting of a sandglass-like "mitotic machine" with microtubules and condensed chromosome. We also found that Ser10 phosphorylated H3 and Thr11 phosphorylated H3 were co-localized at the midbody in two bell-like symmetrical bodies with Ser7 phosphorylated CENP-A during the terminal stage of cytokinesis. Midbody isolation and immunoblotting experiments also indicated that Ser7 phosphorylated CENP-A are components of the midbody. These findings suggest that Ser7 phosphorylated CENP-A acts as a chromosomal passenger protein and may play an important role in cytokinesis.

Trend of dissolved inorganic nitrogen at stations downstream from the Three-Gorges Dam of Yangtze River.

The TRAMO/SEATS program, combined with the Hodrick-Prescott (HP) filter, was used to detect trends and potential change points in time series of dissolved inorganic nitrogen (DIN) at three stations along the Yangtze River. The trend components were extracted, and two change points were successfully detected. The components revealed that DIN has been increasing at all the stations since the 1990s, although variations exist. Changes visible before 2002 illustrate the differences in agriculture development among regions upstream from the stations. The Three-Gorges Dam (TGD), which began to impound in 2003, led to years of different trends. The DIN concentration, which had been trending upward prior to that date, began a slightly downward trend because of NH4(+) depletion. Readings at the Yichang station revealed this trend most strongly; those at the Hankou station less so. The Datong station was far enough away from the TGD so that no obvious effects were seen.

Neurofibromatosis type-1 with retroperitoneal stromal tumour: one case report.

BACKGROUND: Neurofibromatosis with gastrointestinal stromal tumours have been reported several times, while neurofibromatosis with retroperitoneal stromal tumours are very rare. CASE DESCRIPTION: We report the case of a 44-year-old man with a long history of neurofibromatosis. He complained of severe constipation and left leg pain. The patient's examination showed prominent peripheral cutaneous neurofibromas mainly in the belly and limbs, especially a huge mass in his abdomen, no less than ten café-au-lait spots, four Lisch nodules of the iris. Computed tomography and magnetic resonance imaging revealed a round and lobular mass in the retroperitoneal space. It was a well-circumscribed, hypervascular mass with cystic necrosis. A surgical resection was performed, and pathology and immunohistochemistry findings were consistent with stromal tumour. The c-kit gene and platelet-derived growth factor receptor-α gene mutations are not observed in the specimen. CONCLUSIONS: Neurofibromatosis with retroperitoneal stromal tumour is very rare, and radiological, pathological and immunohistochemical examination may identify it. Surgical resection may be the unique method of cure for it.

Knockout of plasminogen activator inhibitor 1 gene reduces amyloid beta peptide burden in a mouse model of Alzheimer's disease.

Accumulation of amyloid beta peptide (Aß) in the brain is a pathological hallmark of Alzheimer's disease (AD); the underlying mechanism, however, is not well understood. In this study, we show that expression of plasminogen activator inhibitor 1 (PAI-1), a physiological inhibitor of tissue type and urokinase type plasminogen activators (tPA and uPA), increases with age in the brain of wild type and Aß precursor protein-presenilin 1 (APP/PS1) transgenic mice as well as in AD patients. Most importantly, we show that knocking out the PAI-1 gene dramatically reduces Aß burden in the brain of APP/PS1 mice but has no effect on the levels of full-length APP, alpha or beta C-terminal fragments. Furthermore, we show that knocking out the PAI-1 gene leads to increases in the activities of tPA and plasmin, and the plasmin activity inversely correlates with the amounts of SDS insoluble Aß40 and Aß42. Together, these data suggest that increased PAI-1 expression/activity contributes importantly to Aß accumulation during aging and in AD probably by inhibiting plasminogen activation and thus Aß degradation.

Oxidative stress and glutathione in TGF-beta-mediated fibrogenesis.

Transforming growth factor beta (TGF-beta) is the most potent and ubiquitous profibrogenic cytokine, and its expression is increased in almost all the fibrotic diseases and in experimental fibrosis models. TGF-beta increases reactive oxygen species production and decreases the concentration of glutathione (GSH), the most abundant intracellular free thiol and an important antioxidant, which mediates many of the fibrogenic effects of TGF-beta in various types of cells. A decreased GSH concentration is also observed in human fibrotic diseases and in experimental fibrosis models. Although the biological significance of GSH depletion in the development of fibrosis remains obscure, GSH and N-acetylcysteine, a precursor of GSH, have been used in clinics for the treatment of fibrotic diseases. This review summarizes recent findings in the field to address the potential mechanism whereby oxidative stress mediates fibrogenesis induced by TGF-beta and the potential therapeutic value of antioxidant treatment in fibrotic diseases.

Dynamic distribution of Thr3-phosphorylated histone H3 in CHO cells in mitosis.

The phosphorylation of histone H3 at Ser10, Ser28, Thr11 and Thr3 of the amino terminal has been proved related to mitosis of the mammalian cells. However, the function of the Thr3 phosphorylation of H3 remains unclear. In this study, indirect immunofluorescence labelling and laser confocal microscopy were used to examine the cellular dynamic distribution of Thr3-phosphorylated H3 at mitosis in CHO cells. The results showed that the Thr3 phosphorylation began at early prophase and spread throughout the chromosomes at late prophase. At metaphase, most of the Thr3-phosphorylated H3 was distributed along the entire chromosomal arms and maintained until early anaphase. During late anaphase and telophase, the fluorescent signal of Thr3-phosphorylated H3 disappeared from chromosomes. There was a precise spatial and temporal correlation between H3 phosphorylation of Thr3 and stages of chromatin condensation. The timing of Thr3 phosphorylation and dephosphorylation in mitosis were similar to that reported for Thr11 phosphorylation of H3. The Thr3-phosphorylated H3 localized along the arms of chromosomes during metaphase and early anaphase. It was different from the Ser10-phosphorylated H3, which localized at telomere regions, and Thr11-phosphorylated H3, which localized at centromeres. The results suggest that the Thr3 phosphorylation of histone H3 may play a specific role, which is different from Ser10 phosphorylation and Thr11 phosphorylation in mitosis.