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Apatite, an important mineral widely distributed in various geological environments, can be used for in situ U–Pb dating and Sr–Nd isotope analyses. The LA-ICPMS U–Pb dating and Sr–Nd isotopic determinations require suitable matrix-matched reference materials. Current apatite standards are rare and have some defects. Most natural apatite references display high and variable common Pb, which may be the most difficult issue in microbeam determination. We provided a gem-quality apatite MAP-3, subjected to detailed major- and trace element composition, U–Pb dating, and Sr–Nd isotopic analyses to assess its homogeneity of chemical composition and suitability as a reference material for microbeam U–Pb dating and Nd isotope analyses. Through comprehensive analyses, we show that the MAP-3 apatite is free of mineral inclusions and is uniform at the level of analytical precision of major- and trace element, U–Pb isotopic, and Nd isotopic ratios despite compositional zones from CL images. The MAP-3 apatite has ID-TIMS determined mean isotopic ratio values of 0.13222 ± 0.00016 for 206Pb/238U, 1.2084 ± 0.0030 for 207Pb/235U, and 0.0663 ± 0.0001 for 207Pb/206Pb and the weighted mean 206Pb/238U ages of 800.5 ± 0.9 Ma (2 s, MSWD = 1.5, n = 11). The 143Nd/144Nd isotopic results determined by (ID)-TIMS are 0.511248 ± 0.000006 (2 s, MSWD = 4.2, n = 11) with moderate Nd contents of ∼1532 ppm. U–Pb age and Nd isotopic compositions obtained by LA-(Q, SF-SC, MC)-ICPMS analysis are reproducible and agree with the values of TIMS, which indicates that MAP-3 apatite has the potential to be a primary reference material for microbeam determination of U–Pb ages and Nd isotope analyses. To validate the effectiveness of the potential, we dated some apatite reference materials of known age and two geological apatites. The results demonstrated the high-quality U–Pb dating reference materials used with MAP-3 apatite. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant extensively escape neutralizing antibodies by vaccines or infection. We assessed serum neutralizing activity in sera from Delta infection after vaccination and Delta infection only against SARS-CoV-2 Wuhan-Hu-1 (WA1), Beta, Delta, and Omicron. Sera from Delta infection only could neutralize WA1 and Delta but almost completely lost capacity to neutralize Beta and Omicron. However, Delta infection after vaccination resulted in a significant increase of serum neutralizing activity against WA1, Beta, and Omicron. This study demonstrates that breakthrough infection of Delta substantially induced high potency humoral immune response against the Omicron variant and other emerged variants. [ABSTRACT FROM AUTHOR]

aims to explore the factors influencing the renal glucose threshold (RTG) in patients with newly diagnosed type 2 diabetes mellitus (T2DM). Methods: A cross-sectional study was conducted on 1009 hospitalized patients with T2DM using stratified random sampling. Blood glucose was monitored using a dynamic blood glucose monitor to obtain the mean blood glucose (MBG), which is used to calculate the RTG. The factors influencing the RTG were then analyzed. Results: The mean RTG in patients with newly diagnosed T2DM was 203.58 ± 55.22 mg/dl. The correlation between the RTG and the various variables was analyzed, and the results demonstrated that the RTG was correlated with the patient's age (r = − 0.14539, P = 0.0001); MBG (r = − 0.35009, P = 0.0001); renal long neck (r = 0.16762, P = 0.0001); homeostatic model assessment for insulin resistance (r = − 0.38322, P = 0.0001); homeostatic model assessment for beta-cell function (r = − 0.22770, P = 0.0001); and the levels of glycated hemoglobin (HbA1c; r = 0.98994, P = 0.0001), blood urea nitrogen (r = − 0.11093, P = 0.0004), creatinine (r = − 0.26414, P = 0.0001), uric acid (r = − 0.20149, P = 0.0001), total cholesterol (r = 0.13192, P = 0.0001), low-density lipoprotein (r = 0.12466, P = 0.0001), thyroid-stimulating hormone (r = − 0.06346, P = 0.0460), beta-2 microglobulin (r = − 0.08884, P = 0.0056), and 24-hour urine glucose (r = 0.32115, P = 0.0001). Multiple linear stepwise regression analysis revealed that the HbA1c, 24-hour urine glucose, estimated glomerular filtration rate (eGFR), D-dimer, and body mass index (BMI) should be included in the final model, and HbA1c had the greatest impact on the RTG followed in descending order by the 24-hour urine glucose, eGFR, D-dimer, and BMI (P < 0.05). Conclusion: The RTG increases in most patients with newly diagnosed diabetes. The risk factors for the RTG are HbA1c, 24-hour urine glucose, eGFR, D-dimer, and BMI. [ABSTRACT FROM AUTHOR]

Data concerning the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic and paucisymptomatic patients are lacking. We report a 3-family cluster of infections involving asymptomatic and paucisymptomatic transmission. Eight of 15 (53%) members from 3 families were confirmed with SARS-CoV-2 infection. Of 8 patients, 3 were asymptomatic and 1 was paucisymptomatic. An asymptomatic mother transmitted the virus to her son, and a paucisymptomatic father transmitted the virus to his 3-month-old daughter. SARS-CoV-2 was detected in the environment of 1 household. The complete genomes of SARS-CoV-2 from the patients were > 99.9% identical and were clustered with other SARS-CoV-2 sequences reported from China and other countries. [ABSTRACT FROM AUTHOR]

We measured antibodies against H7N9 virus 2 years after infection in 14 patients who were infected during October 2016‐September 2017. Approximately 2 years after infection, antibody titers ≥10 were detectable in 13 (92.9%) patients. Three (21.4%) of 14 patients had hemagglutination inhibition titers ≥40, and their geometric mean titer (GMT) was 20 (95% CI 15.7‐28.1), whereas 10 (71.4%) and all 14 (100%) of the 14 patients had titers ≥40, and GMTs at 34.4 (95% CI 25.7‐51.2) and 73.45 (54.7‐106.7) for neuraminidase inhibition and microneutralization antibodies, respectively. Our findings suggest that H7N9 infection may induce long‐term antibody response at least 2 years after infection. [ABSTRACT FROM AUTHOR]

Background: Peripheral nerve injury (PNI) has devastating consequences. Dorsal root ganglion as a pivotal locus participates in the process of neuropathic pain and nerve regeneration. In recent years, gene sequencing technology has seen rapid rise in the biomedicine field. So, we attempt to gain insight into in the mechanism of neuropathic pain and nerve regeneration in the transcriptional level and to explore novel genes through bioinformatics analysis. Methods: The gene expression profiles of GSE96051 were downloaded from GEO database. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and protein–protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software. Results: Our results showed that both IL-6 and Jun genes and the signaling pathway of MAPK, apoptosis, P53 present their vital modulatory role in nerve regeneration and neuropathic pain. Noteworthy, 13 hub genes associated with neuropathic pain and nerve regeneration, including Ccl12, Ppp1r15a, Cdkn1a, Atf3, Nts, Dusp1, Ccl7, Csf, Gadd45a, Serpine1, Timp1 were rarely reported in PubMed database, these genes may provide us the new orientation in experimental research and clinical study. Conclusions: Our results may provide more deep insight into the mechanism and a promising therapeutic target. The next step is to put our emphasis on an experiment level and to verify the novel genes from 13 hub genes. [ABSTRACT FROM AUTHOR]

Puerarin is an active ingredient of pueraria, which has been developed for puerarin injections, used in the treatment of cardiovascular diseases including arrhythmia, myocardial ischemia and hypertension. However, the molecular mechanisms of puerarin on ischemia/reperfusion (I/R)‑induced myocardial apoptosis in diabetic rats are not fully understood. The present study aimed to investigate whether puerarin can attenuate I/R‑induced myocardial apoptosis in diabetic rats, and to investigate the underlying mechanism. A hemodynamic analyzing system was employed to analyze the left ventricular developed pressure (LVDP), the left ventricular end‑systolic interior dimension (LVIDs) and the left ventricular end diastolic interior dimension (LVIDd). ELISA kits were used to analyze malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor‑α (TNF‑α) and interleukin (IL)‑6 levels, NO production and caspase‑3 activity. Nuclear factor (NF)‑κB, ascular endothelial growth factor A (VEGFA), angiotensin (Ang)‑I, phosphorylated (p)‑endothelial nitric oxide synthase protein expression was analyzed using western blot analysis. Puerarin significantly reduced the myocardial infarct area, and increased left ventricular developed pressure in diabetic rats with myocardial I/R. Oxidative stress, inflammation and nuclear factor‑κB protein expression were significantly reduced by puerarin. Furthermore, puerarin activated the protein expression levels of VEGFA and Ang‑I, and increased nitric oxide production, phosphorylated‑endothelial nitric oxide synthase protein expression and caspase‑3 activity. These results demonstrated that the myocardial protective effect of puerarin serves to reduce myocardial I/R injury, via upregulation of VEGFA/Ang‑1 and suppression of apoptosis, in diabetic rats with myocardial I/R. [ABSTRACT FROM AUTHOR]

Long noncoding RNA taurine-upregulated gene 1 (lncRNA TUG1) has been reported to play a key role in the progression of diabetic nephropathy (DN). However, the role of lncRNA TUG1 in the regulation of diabetic nephropathy remains largely unknown. The aim of the present study is to identify the regulation of lncRNA TUG1 on extracellular matrix accumulation via mediating microRNA-377 targeting of PPARγ, and investigate the underlying mechanisms in progression of DN. Microarray was performed to screen differentially expressed miRNAs in db/db DN mice. Afterwards, computational prediction programs (TargetScan, miRanda, PicTar and miRGen) was applied to predict the target gene of miRNAs. The complementary binding of miRNA and lncRNA was assessed by luciferase assays. Protein and mRNA expression were detected by western blot and real time quantitate PCR. MiRNA-377 was screened by miRNA microarray and differentially up-regulated in db/db DN mice. PPARγ was predicted to be the target of miR-377 and the prediction was verified by luciferase assays. Expression of miR-377 was up-regulated in mesangial cell treated with high glucose (25 mM), and overexpression of miR-377 inhibited PPARγ expression and promoted PAI-1 and TGF-β1 expression. The expression of TUG1 antagonized the effect of miR-377 on the downregulation of its target PPARγ and inhibited extracellular matrix accumulation, including PAI-1, TGF-β1, fibronectin (FN) and collagen IV (Col IV), induced by high glucose. LncRNA TUG1 acts as an endogenous sponge of miR-377 and downregulates miR-377 expression levels, and thereby relieving the inhibition of its target gene PPARγ and alleviates extracellular matrix accumulation of mesangial cells, which provides a novel insight of diabetic nephropathy pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Decompressive laminectomy (DI) is a standard operation for lumbar spinal stenosis (LSS) patient with severe claudication symptoms for many years. However, patients whose symptom severity does not meet undergoing invasive surgery make therapeutic options into dilemma. Interspinous spacers (ISP) bridge the gap between surgical interventions and CC in management of LSS. In our study, we aim to systematically assess the two FDA-approved interspinous spacers for treatment of lumbar spinal stenosis: Superion versus X-STOP. Methods: Electronic databases, including PubMed, Embase, MEDLINE, Cochrane Library were searched to retrieve clinical trials concerning the comparison between Superion and X-STOP in treatment for lumbar spinal stenosis before April 2017. The following outcome measures were extracted: (1) Zurich Claudication Questionnaire (ZCQ) patient satisfaction score, (2) axial pain severity, (3) extremity pain severity, (4) back-specific functional impairment, (5) reoperation, and (6) complication. The data analysis was conducted with Review Manager 5.3. Results: Five randomized controlled trials (RCTs) with 1118 patients were included in this meta-analysis. The pooled analysis indicated that the Superion group is superior to X-STOP in axial pain severity (SMD: 0.03; 95% CI 0.15, 0.45; p < 0.0001, I2 = 41%, p = 0.16), ZCQ patient satisfaction score (SMD: 0.23; 95% CI 0.08, 0.38; p = 0.002, I2 = 0%, p = 0.61). However, Superion group showed similarity outcome in extremity pain severity (SMD: 0.18; 95% CI − 0.06, 0.43; p = 0.14, I2 = 62%, p = 0.05), back-specific functional impairment (SMD: 0.04; 95% CI − 0.10, 0.19; p = 0.56, I2 = 0%, p = 0.77), reoperation rate (RR: 1.10; 95% CI 0.82, 1.48; p = 0.51, I2 = 19%, p = 0.30), and complication (RR: 0.98; 95% CI 0.63, 1.53; p = 0.92, I2 = 0%, p = 0.83). Conclusion: Both the Superion and X-STOP interspinous spacers can relieve symptoms of LSS. In addition, the Superion spacer may represent a promising spacer for patient with LSS. As we know, the effectiveness and safety of ISP is still considered investigational and unfavor clinical results in the medical literature may continue to limit the appeal of IPS to many surgeons in the future. However, because of the advantage of IPS technique, it will win a wide place in the future degenerative lumbar microsurgery. [ABSTRACT FROM AUTHOR]

The article focuses on emergence of two variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) -B.1.1.7 in the Great Britain and B.1.351 in South Africa has aroused concern that these variants may escape immunity resulting from either previous infection or vaccination. Topics include the resistance of these variants to neutralization elicited by infection or vaccination, and the virus-based SARSCoV-2 pseudo viruses containing the spike protein of the Wuhan-1 reference strain.

Aminopeptidase H11 present in the surface of intestine microvilli in Haemonchus contortus was identified as the most effective antigen candidate. However, its recombinant forms produced in Escherichia coli , insect cells and yeast could not provide promising protection against H. contortus challenge, probably due to the inappropriate glycosylation and/or conformational folding. Herein, partial H11 containing the potential zinc-binding domain and two predicted glycosylation sites (nt 1 bp–1710 bp, Trans-HPS ) was subcloned downstream of 5′ flanking region of Caenorhabditis elegans cpr-1 gene in pPD95.77 vector, with the deletion of GFP gene. The recombinant was expressed in C. elegans and verified by blotting with anti-H11 and anti-Trans-HPS rabbit polyclonal antibodies and anti-His monoclonal antibody. Stably inherited Trans-HPS in worm descendants was achieved by integration using UV irradiation. Immunization with the crude Trans-HPS extracted from transgenic worms resulted in 37.71% reduction in faecal egg counts (FEC) ( P < 0.05) and 24.91% reduction in worm burden, but an upward curve with moderate rate of daily FEC in goats. These results suggested an apparent delay against H. contortus egg-laying in goats, which differed from that with bacteria-origin form of partial H11 (nt 670 bp–1710 bp, HPS) (26.04% reduction in FEC and 18.46% reduction in worm burden). These findings indicate the feasibility of sufficient C. elegans -expressed H11 for the immunological research and vaccine development. [ABSTRACT FROM AUTHOR]

Zoonotic parasites pose significant health risks globally. In the present study, we combined a microfluidic chip with loop-mediated isothermal amplification (on-chip LAMP) to detect five zoonotic parasites: Toxoplasma gondii , Cryptosporidium parvum , Cryptosporidium hominis , Clonorchis sinensis , and Taenia solium . This method enabled the simultaneous parallel analysis of five genetic markers from a maximum of four samples per chip. The on-chip LAMP assay was conducted in a highly automated format via the addition (by pipetting) of each sample in a single operation. The reaction was performed in volumes as low as 5 μL at a temperature of 65°C for 60 min, achieving limits of detection ranging from 10 -2 to 10 -3  pg./μL of recombinant plasmid DNA. All the time-to-positive values were less than 40 min, and almost all the coefficients of variation were less than 10%, even when using limit of detection concentrations for multiple pathogens, indicating robust reproducibility among replicates. The clinical sensitivity and specificity for detecting 135 field samples were 98.08 and 97.59%, respectively, compared with traditional biological methods, indicating good applicability in the detection of field samples. This on-chip LAMP assay allows for low reagent consumption, ease of operation, and multiple analyses of samples and genetic targets, and is applicable for on-site detection and the routine monitoring of multiple zoonotic parasites., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Lou, Duan, Zhou, Xu, Chen, Chen, Xu, Du and Chen.)

Background: The duration of humoral and T and B cell response after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear., Methods: We performed a cross-sectional study to assess the virus-specific antibody and memory T and B cell responses in coronavirus disease 2019 (COVID-19) patients up to 343 days after infection. Neutralizing antibodies and antibodies against the receptor-binding domain, spike, and nucleoprotein of SARS-CoV-2 were measured. Virus-specific memory T and B cell responses were analyzed., Results: We enrolled 59 patients with COVID-19, including 38 moderate, 16 mild, and 5 asymptomatic patients; 31 (52.5%) were men and 28 (47.5%) were women. The median age was 41 years (interquartile range, 30-55). The median day from symptom onset to enrollment was 317 days (range 257 to 343 days). We found that approximately 90% of patients still have detectable immunoglobulin (Ig)G antibodies against spike and nucleocapsid proteins and neutralizing antibodies against pseudovirus, whereas ~60% of patients had detectable IgG antibodies against receptor-binding domain and surrogate virus-neutralizing antibodies. The SARS-CoV-2-specific IgG+ memory B cell and interferon-γ-secreting T cell responses were detectable in more than 70% of patients., Conclusions: Severe acute respiratory syndrome coronavirus 2-specific immune memory response persists in most patients approximately 1 year after infection, which provides a promising sign for prevention from reinfection and vaccination strategy., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Long non-coding RNA (lncRNA) actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) functions as a competing endogenous RNA to regulate target genes expression by sponging microRNAs (miRs) to play cancer-promoting roles in cancer stem cells. However, the regulatory mechanism of AFAP1-AS1 in cervical cancer (CC) stem cells is unknown. The present study aimed to provide a new therapeutic target for the clinical treatment of CC., Methods: Hyaluronic acid receptor cluster of differentiation 44 variant exon 6 (CD44v6)(+) CC cells were isolated by flow cytometry (FCM). Small interfering RNAs of AFAP1-AS1 (siAFAP1-AS1) were transfected into the (CD44v6)(+) cells. The levels of AFAP1-AS1 were measured by quantitative real-time PCR (qRT-PCR). Sphere formation assay, cell cycle analysis, and Western blotting were used to detect the effect of siAFAP1-AS1. RNA pull-down and luciferase reporter assay were used to verify the relationship between miR-27b-3p and AFAP1-AS1 or vascular endothelial growth factor (VEGF)-C., Results: CD44v6(+) CC cells had remarkable stemness and a high level of AFAP1-AS1. However, AFAP1-AS1 knockdown with siAFAP1-AS1 suppressed the cell cycle transition of G(1)/S phase and inhibited self-renewal of CD44v6(+) CC cells, the levels of the stemness markers octamer-binding transcription factor 4 (OCT4), osteopontin (OPN), and cluster of differentiation 133 (CD133), and the epithelial-mesenchymal transition (EMT)-related proteins Twist1, matrix metalloprotease (MMP)-9, and VEGF-C. In the mechanism study, miR-27b-3p/VEGF-C signaling was demonstrated to be a key downstream of AFAP1-AS1 in the CD44v6(+) CC cells., Conclusions: LncRNA AFAP1-AS1 knockdown inhibits the CC cell stemness by upregulating miR-27b-3p to suppress VEGF-C., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Aims: Whether to perform hybrid surgery (HS) in contrast to anterior cervical discectomy and fusion (ACDF) when treating patients with multilevel cervical disc degeneration remains a controversial subject. To resolve this we have undertaken a meta-analysis comparing the outcomes from HS with ACDF in this condition., Methods: Seven databases were searched for studies of HS and ACDF from inception of the study to 1 September 2019. Both random-effects and fixed-effects models were used to evaluate the overall effect of the C2-C7 range of motion (ROM), ROM of superior/inferior adjacent levels, adjacent segment degeneration (ASD), heterotopic ossification (HO), complications, neck disability index (NDI) score, visual analogue scale (VAS) score, Japanese Orthopaedic Association (JOA) score, Odom's criteria, blood loss, and operating and hospitalization time. To obtain more credible results contour-enhanced funnel plots, Egger's and Begg's tests, meta-regression, and sensitivity analyses were performed., Results: In total, 17 studies involving 861 patients were included in the analysis. HS was found to be superior to ACDF in maintaining C2-C7 ROM and ROM of superior/inferior adjacent levels, but HS did not reduce the incidence of associated level ASD. Also, HS did not cause a higher rate of HO than ACDF. The frequency of complications was similar between the two techniques. HS failed to achieve more favourable outcomes than ACDF using the NDI, VAS, JOA, and Odom's scores. HS did not show any more advantages in operating or hospitalization time but did show reduction in blood loss., Conclusion: Although HS maintained cervical kinetics, it failed to reduce the incidence of ASD. This finding differs from previous reports. Moreover, patients did not show more benefits from HS with respect to symptom improvement, prevention of complications, and clinical outcomes. Cite this article: Bone Joint J 2020;102-B(8):981-996.