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Abstract Background Sleep regularity has been linked to a risk of arterial stiffness (AS). However, the association between sleep regularity indicators, which reflect 24-hour sleep variability, and AS has not yet been examined. Methods We analyzed data from 516 adults, aged 40–65 years (the median age of 51 years), from the ‘Follow-up Study of Sleep Characteristics and Chronic Diseases in the Middle-aged and Elderly Population in Guizhou Province’. Participants underwent assessments of AS (OMRON HBP-8000, baPWV ≥ 1400 cm/s) and sleep (wrist smart band (Honor band 5i) for ≥ 7 days). Logistic regression was utilized to evaluate the odds ratio (OR) and 95% confidence interval (CI) of the association between sleep regularity and AS. Results A total of 516 people were included in this study, of which 279 (54.07%) were in the AS group. The univariate results showed that the AS group (Median 71.18) had lower SRI compared to the No-AS group (Median 75.00) (p

Sperm head morphology is crucial for male factor infertility diagnosis and assessment of male reproductive potential. Several criteria are available to analyze sperm head morphology, but they are limited by poor methodology comparability and population applicability. This study aimed to explore comprehensive and new normal morphometric reference values for spermatozoa heads in fertile Asian males. An automated sperm morphology analysis system captured 23 152 stained spermatozoa from confirmed fertile males. Of these samples, 1856 sperm head images were annotated by three experienced laboratory technicians as “normal”. We employed 14 novel morphometric features to describe sperm head size (head length, head width, length/width ratio, and girth), shape (ellipse intersection over union, girth intersection over union, short-axis symmetry, and long-axis symmetry), area (head, acrosome, postacrosomal areas, and acrosome area ratio), and degrees of acrosome and nuclear uniformity. This straight-forward method for the morphometric analysis of sperm by accurate visual measurements is clinically applicable. The measured parameters present valuable information to establish morphometric reference intervals for normal sperm heads in fertile Asian males. The presented detailed measurement data will be valuable for interlaboratory comparisons and technician training. In vitro fertilization and andrology laboratory technicians can use these parameters to perform objective morphology evaluation when assessing male fertilization potential.

Abstract Neural networks are frequently employed to model species distribution through backpropagation methods, known as backpropagation neural networks (BPNN). However, the complex structure of BPNN introduces parameter settings challenges, such as the determination of connection weights, which can affect the accuracy of model simulation. In this paper, we integrated the Grey Wolf Optimizer (GWO) algorithm, renowned for its excellent global search capacity and rapid convergence, to enhance the performance of BPNN. Then we obtained a novel hybrid algorithm, the Grey Wolf Optimizer algorithm optimized backpropagation neural networks algorithm (GNNA), designed for predicting species’ potential distribution. We also compared the GNNA with four prevalent species distribution models (SDMs), namely the generalized boosting model (GBM), generalized linear model (GLM), maximum entropy (MaxEnt), and random forest (RF). These models were evaluated using three evaluation metrics: the area under the receiver operating characteristic curve, Cohen’s kappa, and the true skill statistic, across 23 varied species. Additionally, we examined the predictive accuracy concerning spatial distribution. The results showed that the predictive performance of GNNA was significantly improved compared to BPNN, was significantly better than that of GLM and GBM, and was even comparable to that of MaxEnt and RF in predicting species distributions with small sample sizes. Furthermore, the GNNA demonstrates exceptional powers in forecasting the potential non-native distribution of invasive plant species.

Abstract CD4+CD25+ regulatory T cells (Tregs) play an important role in maintaining immune homeostasis in multiple sclerosis (MS). Hence, we aimed to explore the therapeutic efficacy and safety of adoptive cell therapy (ACT) utilizing induced antigen-specific Tregs in an animal model of MS, that is, in an experimental autoimmune encephalomyelitis (EAE) model. B cells from EAE model that were activated with soluble CD40L were used as antigen-presenting cells (APCs) to induce the differentiation of antigen-specific Tregs from naïve CD4 precursors, and then, a stepwise isolation of CD4+CD25highCD127low Tregs was performed using a flow sorter. All EAE mice were divided into Treg-treated group (2 × 104 cells in 0.2 mL per mouse, n = 14) and sham-treated group (0.2 mL normal saline (NS), n = 20), which were observed daily for clinical assessment, and for abnormal appearance for 6 weeks. Afterward, histological analysis, immunofluorescence and real-time PCR were performed. Compared to sham-treated mice, Treg-treated mice exhibited a significant decrease in disease severity scores and reduced inflammatory infiltration and demyelination in the spinal cord. Additionally, Tregs-treated mice demonstrated higher CCN3 protein and mRNA levels than sham-treated mice. The results of this preclinical study further support the therapeutic potential of this ACT approach in the treatment of MS.

This work reported gold nanoparticles (AuNPs)-based colorimetric immunoassay with the Cu-based metal–organic framework (MOF) to load pyrroloquinoline quinone (PQQ) for the catalytic oxidation of cysteine. In this method, both Cu2+ and PQQ in the MOF could promote the oxidation of inducer cysteine by redox cycling, thus limiting the cysteine-induced aggregation of AuNPs and achieving dual signal amplification. Specifically, the recombinant carcinoembryonic antigen (CEA) targets were anchored on the MOF through the metal coordination interactions between the hexahistidine (His6) tag in CEA and the unsaturated Cu2+ sites in MOF. The CEA/PQQ-loaded MOF could be captured by the antibody-coated ELISA plate to catalyze the oxidation of cysteine. However, once the target CEA in the samples bound to the antibody immobilized on the plate surface, the attachment of CEA/PQQ-loaded MOF would be limited. Cysteine remaining in the solution would trigger the aggregation of AuNPs and cause a color change from red to blue. The target concentration was positively related to the aggregation and color change of AuNPs. The signal-on competitive plasmonic immunoassay exhibited a low detection limit with a linear range of 0.01–1 ng/mL. Note that most of the proteins in commercial ELISA kits are recombinant with a His6 tag in the N- or C-terminal, so the work could provide a sensitive plasmonic platform for the detection of biomarkers.

AIM: To evaluate the predicative factors of visual prognosis using optical coherence tomography angiography (OCTA) in ischemic branch retinal vein occlusion (BRVO) patients with macular edema (ME) after anti-vascular endothelial growth factor (VEGF) treatment. METHODS: In this retrospective analysis, data from 60 patients (60 eyes) with a definite diagnosis of ischemic BRVO with ME by fundus fluorescein angiography (FFA) were studied. The eyes with ME according to spectral domain optical coherence tomography (SD-OCT) underwent intravitreal conbercept (IVC) and 3+pro re nata (PRN) regimen. The injection times were recorded. Two weeks after injection, fundus laser photocoagulation was performed in the non-perfusion area of the retina. The patients were followed up once a month for 6mo. The best-corrected visual acuity (BCVA), foveal avascular zone (FAZ), and A-circularity index (AI), at 6mo and the baseline were compared. RESULTS: All patients showed significant improvement in BCVA from 0.82±0.32 to 0.39±0.11 logMAR (P

AIM: To investigate blood flow density within 300μm(FD-300)around the foveal avascular zone(FAZ)in optical coherence tomography angiography(OCTA)of patients with macular edema(ME)complicated with non-ischemic branch retinal vein occlusion(BRVO), and to explore and evaluate the predictive effect of this parameter on the number of intraocular drug injections.METHODS: A retrospective case study. A total of 50 patients(50 eyes)who were diagnosed as non-ischemic BRVO combined with ME and received intravitreal conbercept(IVC)in the Affiliated Eye Hospital of Nanjing Medical University from January 2021 to March 2022 were selected, and they were treated with 3+PRN regimen. The 25 cases(25 eyes)treated with intraocular injection ≤5 times were classified as group B, and 25 cases(25 eyes)treated with intraocular injection >5 times were classified as group C, and 25 fellow eyes were randomly selected as control group A. OCTA was used to scan the macular area in 3mm×3mm to collect images of retinal blood flow, the central macular thickness(CMT)and FD-300. The CMT, best-corrected visual acuity(BCVA), and FD-300 were compared between the two groups at baseline, 1, 3, 6 and 12mo after the third injection.RESULTS: The BCVA(LogMAR)of the affected eye in both groups B and C at 1, 3, 6 and 12mo after the third injection was significantly lower than baseline(all P

Abstract Background The aim of this article is to establish an external quality assessment (EQA) scheme for sperm Deoxyribonucleic acid (DNA) fragmentation (SDF) detection, and to assess the feasibility of the scheme. In addition, this article provides some case analysis of abnormal results in order to really help improve the performance of the laboratory. Results In 2021 and 2022, 10 and 28 laboratories in China volunteered to participate in the EQA program respectively. Two samples were selected for EQA each year, a large spread of results was obtained for the four samples, and the highest values were 13.7, 4.2, 8.0 and 4.0 times the lowest respectively. The coefficients of variation (CVs) were very high for the four samples, at 46.6%, 30.1%, 26.7% and 30.3%, respectively. The CVs of the samples with high SDF values were lower than those of the samples with low SDF values. There was no significant difference between the results of sperm chromatin structure assay (SCSA) and sperm chromatin dispersion (SCD). For the 10 laboratories that participated in EQA in 2021 and 2022, the CVs of low SDF value samples and high SDF value samples decreased from 46.6% and 30.1% in 2021 to 32.5% and 22.7% in 2022, respectively. Conclusion This is the first study to evaluate the EQA program on SDF, which involved a number of laboratories and was demonstrated to be feasible. It is recommended that all laboratories participate in the EQA of SDF to ensure the accuracy of the results.

Abstract Several studies have reported an association between dipeptidyl peptidase 4 inhibitor (DPP4i), a commonly prescribed second‐line oral antihyperglycemic drug, and bullous pemphigoid (BP). However, the benefits of DPP4i withdrawal in patients with BP remain controversial. This study primarily aimed to evaluate the clinical severity of DPP4i‐associated BP by comparing it to those without Type 2 diabetes mellitus (DM). The secondary objective was to determine whether cessation of DPP4i is necessary for all patients with BP. This retrospective case–control study included 83 patients. The participants were divided into three groups according to their diabetic status and the status of discontinuance or continuance of DPP4i. The 12‐month follow‐up of the monthly dosage of systemic steroids per body weight (kg) and the percentage of systemic steroid off‐therapy in these participants were recorded since the diagnosis of BP. Compared to patients with BP without DM, the 1st, 3rd, and 12th systemic prednisolone doses were significantly lower in the DPP4i group (p = 0.01684, 0.02559, and 0.009336, respectively). The 12th systemic prednisolone dose was significantly lower in patients who discontinued DPP4i (p = 0.0338). Nevertheless, several spontaneous remissions with systemic steroid off‐therapy were also noted in the DPP4i‐continuance group within 12 months of follow‐up. This article supports the favorable impact of DPP4i withdrawal in patients with BP and shows that DPP4i may incite or aggravate BP, resulting in a milder disease course.

AIM:To investigate the changes in the macular microvasculature in eyes with central retinal artery occlusion(CRAO)and paracentral acute middle maculopathy(PAMM).METHODS: Retrospective study. A total of 27 cases(27 eyes)who diagnosed with CRAO-PAMM and 29 patients(29 eyes)diagnosed as CRAO but with no PAMM were hospitalized in our hospital from January 2020 to December 2021. There were 33 normal people(33 eyes)who underwent physical examination in our hospital selected as control group. Optical coherence tomography angiography(OCTA)was used to measure retinal blood flow and thickness parameters in the 3 mm×3 mm area of the macula. The correlation among macular retinal blood flow density, retinal thickness, foveal avascular zone(FAZ)area, FAZ perimeter, acircularity index(AI), flow density in a 300-μm-wide region around the FAZ(FD-300)and lesion area, best corrected visual acuity(BCVA)in the CRAO-PAMM group was analyzed.RESULTS: Among the three groups, there were significant differences in the overall and parafoveal blood flow density of superficial capillary layer(SCP)and deep capillary layer(DCP), foveal thickness, FAZ area, FAZ perimeter, AI and FD-300(all P

This work prepared porous carbon with excellent electrochemical performance using hydrothermal and carbonization methods. Specifically, caragana was used as carbon precursor, hydrazine hydrate as nitrogen source, and nickel acetate as nickel source during this preparation process. The results showed that porous carbon carbonized at 700 °C has excellent surface area (1779 m2 g−1), moderate oxygen content (7.88 at%), and nitrogen content (1.64 at%), which are conducive to improving pseudocapacitance. The N4NiPC180-3 has specific capacitance of 427 F g−1 at 0.5 A g−1, and high capacitance retention of 74.3% even at 20 A g−1. The retention rate after 10,000 cycles is 97.4%, verifying its excellent cycling stability. In addition, the N4NiPC180-3 in the two-electrode system test can achieve an energy density of 35.8 W h kg−1 at a power density of 500.1 W kg−1. This work extends high value-added utilization of biomass derivatives in energy storage applications.

AIM: To observe the imaging characteristics of multi-modal imaging in perifoveal exudative vascular anomalous complex(PEVAC).METHODS: A retrospective case analysis. There were 11 patients(11 eyes)diagnosed as PEVAC by multi-modal imaging in our hospital included in this study from February 2021 to February 2022. All patients underwent the examinations of best corrected visual acuity(BCVA), fundus photography, fluorescein fundus angiography(FFA), spectral-domain optical coherence tomography(SD-OCT)and optical coherence tomography angiography(OCTA).RESULTS: On fundus examination, six out of eleven eyes presented as a unilateral and isolated lesion with diameter ≥150μm, five out of eleven eyes presented as multiple lesions(ranging from 2 to 4)and the diameter of each lesion

A green and effective nitrogen and nickel in-situ doping strategy was designed to prepare cellulose-based N/Ni co-doped porous carbon (PC). The co-hydrothermal pretreatment induced by hydrazine hydrate and nickel acetate effectively modifies the physico-chemical structure of PC and further improves its electrochemical performance. The efficient N-supply and unique heteroatom regulation performance of hydrazine hydrate is related to its strong reducibility. The specific surface area and total pore volume of the synthesized N4NiPC220-3 are 1383.66 m2 g−1 and 0.59 cm3 g−1, while the N and O contents are 1.35 and 10.41%, respectively. At current densities of 0.5 and 20 A g−1, N4NiPC220-3 exhibits a high specific capacitance of 415 F g−1 and a good capacitance retention of 72.22%, respectively. After 10,000 charge/discharge cycles, the retention rate is as high as 96.06%, confirming its excellent cycling stability. The two-electrode system test results further show that the energy density of N4NiPC220-3 is as high as 35.6 W h kg−1 at a power density of 500.1 W kg−1, while a high retention rate of 87.87% is still obtained after 10,000 cycles. This green and efficient synthesis method based on in-situ co-doping of hydrazine hydrate and nickel acetate is a promising alternative strategy for producing carbon-based supercapacitors.

BackgroundIncreasing evidence indicates the importance of CD8+ T cells in autoimmune attack against CNS myelin and axon in multiple sclerosis (MS). Previous research has also discovered that myelin-reactive T cells have memory phenotype functions in MS patients. However, limited evidence is available regarding the role of CD8+ memory T cell subsets in MS. This study aimed to explore potential antigen-specific memory T cell-related biomarkers and their association with disease activity.MethodsThe myelin oligodendrocyte glycoprotein (MOG)-specific CD8+ memory T cell subsets and their related cytokines (perforin, granzyme B, interferon (IFN)-γ) and negative co-stimulatory molecules (programmed cell death protein 1 (PD-1), T- cell Ig and mucin domain 3 (Tim-3)) were analyzed by flow cytometry and real-time PCR in peripheral blood of patients with relapsing-remitting MS.ResultsWe found that MS patients had elevated frequency of MOG-specific CD8+ T cells, MOG-specific central memory T cells (TCM), MOG-specific CD8+ effector memory T cells (TEM), and MOG-specific CD8+ terminally differentiated cells (TEMRA); elevated granzyme B expression on MOG-specific CD8+ TCM; and, on MOG-specific CD8+ TEM, elevated granzyme B and reduced PD-1 expression. The Expanded Disability Status Scale score (EDSS) in MS patients was correlated with the frequency of MOG-specific CD8+ TCM, granzyme B expression in CD8+ TCM, and granzyme B and perforin expression on CD8+ TEM, but with reduced PD-1 expression on CD8+ TEM.ConclusionThe dysregulation of antigen-specific CD8+ memory T cell subsets, along with the abnormal expression of their related cytokines and negative co-stimulatory molecules, may reflect an excessive or persistent inflammatory response induced during early stages of the illness. Our findings strongly suggest positive regulatory roles for memory T cell populations in MS pathogenesis, probably via molecular mimicry to trigger or promote abnormal peripheral immune responses. Furthermore, downregulated PD-1 expression may stimulate a positive feedback effect, promoting MS-related inflammatory responses via the interaction of PD-1 ligands. Therefore, these parameters are potential serological biomarkers for predicting disease development in MS.

AIM: To observe the efficacy of intravitreal anti-vascular endothelial growth factor(VEGF)injection treatment in chronic central serous chorioretinopathy(CCSC)combined with choroidal neovascularization(CNV)using multimodal imaging, to explore and evaluate the influence factors.METHODS: In this retrospective study, 30 patients(30 eyes)were diagnosed as CCSC combined with CNV. Comprehensive ophthalmologic examinations were performed, including best corrected visual acuity(BCVA), enhanced-depth imaging(EDI)spectral domain optical coherence tomography(SD-OCT), fundus fluorescein angiography(FFA), Indocyanine green angiography(ICGA), and optical coherence tomography angiography(OCTA). Patients were treated with intravitreal ranibizumab(IVR)parallel 1+PRN schem for subretinal fluid(SRF)secondary to CCSC combined with CNV. All the patients were followed up at 1wk, 1mo after treatment and 3mo after consecutive treatment. The BCVA, central macular thickness(CMT), subfoveal choroid thickness(SFCT)and CNV flow area were compared.RESULTS: All the patients were observed at baseline, 1wk, 1mo after treatment and 3mo after consecutive treatment. The difference at various time points of CMT(μm)were statistically significant(F=62.06, P

Abstract Neuropathic pain (NP) is a long‐term recurrent disease caused by somatosensory nervous system injury, with spontaneous pain, hyperalgesia, ectopic pain, and paresthesia as the main clinical manifestations. It adversely affects patients' quality of life. NP treatments often include medication, physical therapy, and invasive therapy; the first two therapies are generally ineffective for some NP patients. These patients sometimes rely on invasive therapy to alleviate pain. Spinal cord stimulation (SCS) is a very effective therapeutic method. SCS is a neuroregulatory method that involves placing the electrodes on the corresponding painful spinal cords. Pain is greatly alleviated after SCS. SCS has been proven to be an effective therapeutic method for the treatment of neurological pain. Furthermore, SCS provides a feasible approach for patients with unsuccessful drug treatment. This paper reviews the relevant literature of spinal cord electrical stimulation, focusing on the mechanism of action, clinical application, clinical efficacy and technical progress of spinal cord electrical stimulation. SCS is widely used in the treatment of NP diseases such as postherpetic neuralgia, back surgery failure syndrome, and phantom limb pain. With advancements in science and technology, tremendous progress has also been made in the spinal cord electrical stimulation method and good momentum has been maintained.

Abstract Headache is a common refractory disorder among adults, especially in females, which can lower the quality of life in patients and increase medical costs. Nearly 90% of people have been affected by headache disorders during their lifetime. The severe situation of headaches has drawn the attention of researchers in recent years. Although the mechanism of headache has not been fully understood by us, there are many effective preventive drugs and treatments available. This review is aimed to sum up the progress in clinical trials of headaches in the past 5 years.

Abstract The loss of neuronal in the substantia nigra of the elderly contributes to striatal damage and plays a critical part in the common forms of neurodegenerative diseases such as Parkinson disease (PD). The deficit of dopamine is one of the most familiar neuropathological features of PD as well as α‐Synuclein aggregation. The peripheral autonomic nervous system is also affected negatively during the course of the disease, although the subsistent of dyskinesias and else major motor characteristic deficits take significant role in the diagnostic methods during clinical practice, which is related to a number of non‐motor symptoms that might increase aggregate risks. Multiple pathways and mechanisms are involved in the molecular pathogenesis: α‐Synuclein, neuronal homeostasis, mitochondrial function, oxidative stress, as well as neuroinflammation. Investigations in the last few years for diagnostic biomarkers used neuroimaging, including single photon emission computed tomography as well as cutting‐edge magnetic resonance imaging techniques, which has been presented to facilitate discrepant diagnosis. Pharmacological treatment is also important and efficient in equal measure. In addition to reliance on striatal dopamine replacement therapy, many solutions that are used for motor or nonmotor symptoms in these patients are available.

ObjectiveThis study aimed to explore risk factors, clinical features, and prognosis of patients with hypertrophic cardiomyopathy (HCM) complicated by ischemic stroke (IS).MethodsWe conducted a retrospective analysis of all HCM patient data and a 1-year follow-up study.ResultsTotally, 506 patients with HCM, including 71 with IS, were enrolled. Older age (≥63 years) was associated with an increased risk of IS in HCM patients (OR = 1.045, 95% CI: 1.018–1.072, p = 0.001). Among 37 patients complicated by IS, 22 (59.5%, 22/37) manifested as cardioembolism (CE) subtype, and 13 (35.1%, 3/37) small artery occlusion (SAO) subtype, according to TOAST classification. In the acute phase, the IS patients presented with NIHSS 4 (interquartile range: 1, 10). Multi-infarction was more common than single infarction (72.7 vs. 27.3%), while cortical + subcortical infarction (CE group: 50%) or subcortical infarction (SAO group: 53.8%) constituted most IS cases. Additionally, the blood supply areas of anterior circulation (CE group: 45.5%; SAO group: 92.3%) or anterior + posterior circulation (CE group: 50%) were mainly involved. The 1-year survival rate of HCM patients with concomitant IS was 81.8%, and IS was associated with 1-year all-cause death in HCM patients (HR = 5.689, 95% CI: 1.784–18.144, p = 0.003).ConclusionOlder age is a risk factor for IS occurrence in HCM patients. Patients with HCM complicated by IS had mild or moderate neurologic deficits at disease onset. CE and SAO subtypes predominate in patients with concomitant IS, especially the former. Multiple cortical and subcortical infarctions are their neuroimaging characteristics, mainly involving the anterior circulation or anterior + posterior circulation. Is is a risk factor for all-cause death in HCM patients within 1 year.

Abstract Background As an autoimmune systemic disorder, rheumatoid arthritis (RA) features chronic inflammation as well as synovial infiltration of immune cells. This study was designed with the purpose of discussing the hidden mechanism of SPTBN1 and exploring favorable molecular‐targeted therapies. Methods With the application of RT‐qPCR and western blot, the expressions of SPTBN1 and PIK3R2 before or after transfection were estimated. Besides, Cell Counting Kit‐8, Edu, wound healing, transwell, enzyme‐linked immunosorbent assay, and TUNEL were adopted for the evaluation of the viability, proliferation, migration, invasion, inflammatory response, and apoptosis of fibroblast‐like synoviocyte (FLS). In addition, the interaction of SPTBN1 and PIK3R2 was testified by applying immunoprecipitation (IP) and western blot was utilized for the assessment of migration‐, apoptosis‐, and PI3K/AKT signal‐related proteins. Results It was discovered that SPTBN1 declined in RA synovial cells and its overexpression repressed the proliferation, migration, invasion, and inflammation of RA‐FLSs but promoted apoptosis. IP confirmed that SPTBN1 could bind to PIK3R2 in FLSs. To further figure out the hidden mechanism of SPTBN1 in RA, a series of functional experiments were carried out and the results demonstrated that the reduced expressions of MMP2, MMP9, IL‐8, IL‐1β, IL‐6, and Bcl2 as well as increased levels of Bax and cleaved caspase3 in SPTBN1‐overexpressed RA‐FLSs were reversed by PIK3R2 depletion, revealing that SPTBN1 repressed the migration and inflammation and promoted the apoptosis of RA‐FLSs via binding to PIK3R2. Results obtained from western blot also revealed that PIK3R2 interference ascended the contents of p‐PI3K and p‐AKT in SPTBN1‐overexpressed RA‐FLSs, implying that SPTBN1 repressed PI3K/AKT signal in RA via PIK3R2. Discussion SPTBN1 alleviated the proliferation, migration, invasion, and inflammation in RA via interacting with PIK3R2.

Background: Brain exposure to ionizing radiation during the radiotherapy of brain tumor or metastasis of peripheral cancer cells to the brain has resulted in cognitive dysfunction by reducing neurogenesis in hippocampus. The water extract of Lycium barbarum berry (Lyc), containing water-soluble Lycium barbarum polysaccharides and flavonoids, can protect the neuronal injury by reducing oxidative stress and suppressing neuroinflammation. Reseach Design: To demonstrate the long-term radioprotective effect of Lyc, we evaluated the neurobehavioral alterations and the numbers of NeuN, calbindin (CB), and parvalbumin (PV) immunopositive hippocampal neurons in BALB/c mice after acute 5.5 Gy radiation with/without oral administration of Lyc at the dosage of 10 g/kg daily for 4 weeks. Results: The results showed that Lyc could improve irradiation-induced animal weight loss, depressive behaviors, spatial memory impairment, and hippocampal neuron loss. Immunohistochemistry study demonstrated that the loss of NeuN-immunopositive neuron in the hilus of the dentate gyrus, CB-immunopositive neuron in CA1 strata radiatum, lacunosum moleculare and oriens, and PV-positive neuron in CA1 stratum pyramidum and stratum granulosum of the dentate gyrus after irradiation were significantly improved by Lyc treatment. Conclusion: The neuroprotective effect of Lyc on those hippocampal neurons may benefit the configuration of learning related neuronal networks and then improve radiation induced neurobehavioral changes such as cognitive impairment and depression. It suggests that Lycium barbarum berry may be an alternative food supplement to prevent radiation-induced neuron loss and neuropsychological disorders.

Glycolysis produces large amounts of adenosine triphosphate (ATP) in a short time. The retinal vascular endothelium feeds itself primarily through aerobic glycolysis with less ATP. But when it generates new vessels, aerobic glycolysis provides rapid and abundant ATP support for angiogenesis, and thus inhibition of glycolysis in endothelial cells can be a target for the treatment of neovascularization. Aerobic glycolysis has a protective effect on Müller cells, and it can provide with a target for visual protection and maintenance of the blood-retinal barrier. Under physiological conditions, the mitochondria of RPE can use lactic acid produced by photoreceptor cells as an energy source to provide ATP for survival. In pathological conditions, because RPE cells avoid their oxidative damage by increasing glycolysis, a large number of glycolysis products accumulate, which in turn has a toxic effect on photoreceptor cells. This shows that stabilizing the function of RPE mitochondria may become a target for the treatment of diseases such as retinal degeneration. The decrease of aerobic glycolysis leads to the decline of photoreceptor cell function and impaired vision; therefore, aerobic glycolysis of stable photoreceptor cells provides a reliable target for delaying vision loss. It is of great significance to study the role of glycolysis in various retinal cells for the targeted treatment of ocular fundus diseases.

IntroductionChimeric antigen receptor (CAR) T-cell (CAR-T) therapy followed by haploidentical hematopoietic stem cell transplantation (haplo-HSCT) markedly improves the long-term survival of patients with refractory/relapsed (R/R) B-cell acute lymphoblastic leukemia (B-ALL).MethodsWe performed a parallel comparison of transplant outcomes in 168 B-ALL patients undergoing haplo-HSCT after achieving minimal residual disease (MRD)-negative complete remission (CR) from CAR-T therapy (n = 28) or chemotherapy (n = 140) between January 2016 and August 2021. We further divided the chemotherapy group into the first CR group (chemo+CR1, n = 118) and a second or more CR group (chemo+≥CR2, n = 22).ResultsWith a median follow-up period of 31.0 months, the 2-year overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM), and relapse rates in the CAR-T and chemotherapy groups did not differ significantly (OS, 87.9% vs. 71.5 %; LFS, 72.0% vs. 66.8%; NRM, 3.9% vs. 13.7%; relapse, 24.1% vs. 19.4%). Multivariate analysis confirmed that ≥CR2 at transplantation following chemotherapy was an independent risk factor associated with poor OS (hazard ratio (HR) 4.22 [95% CI, 1.34–13.293], p = 0.014) and LFS (HR 2.57 [95% CI, 1.041–6.343], p = 0.041). The probabilities of OS and LFS at 2 years in the CAR-T group were comparable to those in the chemo+CR1 group but significantly higher than those in the chemo+≥CR2 group (OS, 87.9% vs. 37.8%, p = 0.007; LFS, 72.0% vs. 41.7%, p = 0.043). No significant differences in the incidences of NRM were noted among the three groups.ConclusionsOur results demonstrated that patients with R/R B-ALL receiving haplo-HSCT after CAR-T therapy achieved comparable outcomes to patients transplanted post-chemotherapy-based MRD-negative CR1, without increased risk of transplant-related mortality and toxicity.

The neuron loss caused by the progressive damage to the nervous system is proposed to be the main pathogenesis of neurodegenerative diseases. Ependyma is a layer of ciliated ependymal cells that participates in the formation of the brain-cerebrospinal fluid barrier (BCB). It functions to promotes the circulation of cerebrospinal fluid (CSF) and the material exchange between CSF and brain interstitial fluid. Radiation-induced brain injury (RIBI) shows obvious impairments of the blood–brain barrier (BBB). In the neuroinflammatory processes after acute brain injury, a large amount of complement proteins and infiltrated immune cells are circulated in the CSF to resist brain damage and promote substance exchange through the BCB. However, as the protective barrier lining the brain ventricles, the ependyma is extremely vulnerable to cytotoxic and cytolytic immune responses. When the ependyma is damaged, the integrity of BCB is destroyed, and the CSF flow and material exchange is affected, leading to brain microenvironment imbalance, which plays a vital role in the pathogenesis of neurodegenerative diseases. Epidermal growth factor (EGF) and other neurotrophic factors promote the differentiation and maturation of ependymal cells to maintain the integrity of the ependyma and the activity of ependymal cilia, and may have therapeutic potential in restoring the homeostasis of the brain microenvironment after RIBI or during the pathogenesis of neurodegenerative diseases.

AIM: To further explore effective drugs for dry eye treatment by isolating and culturing lacrimal gland epithelial cells in vitro, establishing a dry eye cell model and analyzing relevant inflammatory factors. METHODS: Rabbit lacrimal gland epithelial cells were in vitro isolated and cultured, and the activity and purity of primary cells were identified by cell proliferation experiment and immunofluorescence experiment. In addition, 0.5 times IC50 of lipopolysaccharide LPS and TNF-α were used respectively to stimulate rabbit lacrimal gland epithelial cells and then establish two dry eye cell models. Finally, through cell proliferation experiment, ELISA and flow cytometry, the biological characteristics of these two dry eye cell models were compared. RESULTS:After 12h of culture, the primary cells of lacrimal gland epithelial cells basically adhered to the wall of culture bottles; and 48h later, the cells stretched and almost each of them presented a shape of a long triangle. The activity of primary cells of lacrimal gland epithelium was 92%, and the positive rate of marker Pan-rkeratin was more than 90%, which accorded with the experimental requirements. The IC50 of LPS and TNF-α are 20μg/mL and 4.996ng/mL respectively. After 12h of intervention with LPS(10μg/mL)and TNF-α(2.5ng/mL), the cell activity of the two groups was significantly lower than that of control group(P

Adult hippocampal neurogenesis (AHN) is suppressed by chronic stress. The negative effect of stress is mainly attributed to increased levels of stress hormones (e.g. glucocorticoids, GCs). Exercise enhances AHN, yet it also stimulates GC secretion. To delineate the paradoxical role of GCs, we took the advantage of a unique mouse strain (L/L) which exhibits an inert response to stress-induced secretion of GCs to study the role of GCs in exercise-induced AHN. Our results showed that basal corticosterone (CORT), the main GCs in rodents, levels were similar between the L/L mice and wild-type (WT) mice. However, levels of CORT in the L/L mice were barely altered and significantly lower than those of the WT mice during treadmill running (TR). AHN was enhanced by 4 weeks of TR in the WT mice, but not L/L mice. WT mice that received daily injection of CORT to evoke serum CORT levels similar to those during exercise for 4 weeks did not affect AHN, whereas injection with large amount of CORT inhibited AHN. Taken together, our results indicated that exercise-related elevation of CORT participates in exercise-enhanced AHN. CORT alone is not sufficient to elicit AHN and may inhibit AHN if the levels are high.

Abstract Background A consensus has been reached that carbapenem-resistant Enterobacteriaceae (CRE) screening in immunosuppressed individuals can reduce the incidence of CRE bloodstream infection (BSI). Methods We retrospectively studied the clinical data of 395 consecutive HSCT patients from September 2017 to April 2019. From September 2017 to June 2018 (period 1), 200 patients received single CRE screening before transplantation. From July 2018 to April 2019 (period 2), 195 patients received continuous weekly CRE screening after admission. For patients colonized with CRE, targeted managements were received: (1) contact precautions and (2) preemptive CRE-targeted treatment if necessary. Results During period 1, 3 patients with CRE colonization were detected (1.5%). The CRE BSI rate was 2.0% (4 patients), and the related 30-day mortality was 50.0% (2 out of 4 patients). During period 2, 21 patients with CRE colonization were detected, and the detection rate was significantly higher than that in period 1 (P

As a pentacyclic triterpene, MA exhibits effective free radical scavenging capabilities. The purpose of this study was to explore the effects of MA on porcine early-stage embryonic development, oxidation resistance and mitochondrial function. Our results showed that 1 μM was the optimal concentration of MA, which resulted in dramatically increased blastocyst formation rates and improvement of blastocyst quality of in vitro-derived embryos from parthenogenetic activation (PA) and somatic cell nuclear transfer (SCNT). Further analysis indicated that MA supplementation not only significantly decreased the abundance of intracellular reactive oxygen species (ROS) and dramatically increased the abundance of intracellular reductive glutathione (GSH) in porcine early-stage embryos, but also clearly attenuated mitochondrial dysfunction and inhibited apoptosis. Moreover, Western blotting showed that MA supplementation upregulated OCT4 (p < 0.01), SOD1 (p < 0.0001) and CAT (p < 0.05) protein expression in porcine early-stage embryos. Collectively, our data reveal that MA supplementation exerts helpful effects on porcine early embryo development competence via regulation of oxidative stress (OS) and amelioration of mitochondrial function and that MA may be useful for increasing the in vitro production (IVP) efficiency of porcine early-stage embryos.

Objective: We conducted a survey to assess vaccination coverage, vaccination willingness, and variables associated with vaccination hesitancy to provide evidence on coronavirus disease (COVID-19) vaccination strategies.Methods: This anonymous questionnaire study conducted a multicenter, cross-sectional survey of outpatients and inpatients with epilepsy (PWE) registered in epilepsy clinics, in 2021, in 10 hospitals in seven cities of Shandong Province.Results: A total of 600 questionnaires were distributed, and 557 valid questionnaires were returned. A total of 130 people were vaccinated against COVID-19. Among 427 unvaccinated participants, 69.32% (296/427) were willing to receive the COVID-19 vaccine in the future, and the remaining 30.68% (131/427) were unwilling to receive vaccination. Most (89.9%) of the participants believed that the role of vaccination was crucial in response to the spread of COVID-19. A significant association was found between willingness to receive the COVID-19 vaccine and the following variables: age, marital status, level of education, occupation, residence, seizure type, and seizure control after antiepileptic drug therapy. It is noteworthy that education level, living in urban areas, and seizure freedom were significantly related to willingness to receive COVID-19 vaccination.Conclusions: Vaccination is a key measure for the prevention and control of COVID-19, and most PWE are willing to be vaccinated. Vaccine safety, effectiveness, and accessibility are essential in combatting vaccine hesitation and increasing vaccination rates.

In light of the gap in the national identity research, this study proposes, constructs, and examines the path to national identity by using a mixed-method approach. Study 1 collected 502 questionnaires from Chinese tourists, and Study 2 conducted semi-structured interviews with 15 tourists. The findings confirm that cultural and creative tourism contributes to the construction of tourists’ national identity. Tourists’ long-term implicit cultural memory and short-term explicit cultural learning are the double guarantees for forming tourists’ cultural identity. Importantly, tourists’ cultural identity plays a critical mediating role in promoting national identity. Moreover, the interactive effect of cultural experience and creative performance accelerates the construction process of tourists’ national identity. This study consolidates the sociopolitical significance of cultural and creative tourism for national identity through a rare mixed method and identifies the specific role of the cultural factors affecting national identity, thereby providing great theoretical contributions and practical value.

Nipple adenoma is a rare benign tumor of the nipple due to mammary proliferation of the lactiferous ducts. Common presentation of the tumor includes nipple erosion, erythema, scaling, and eczematous change of the overlying skin. Delayed diagnosis is common since its clinical presentation resembles that of other benign or malignant condition of the nipple, such as nipple eczema or Paget's disease. Timely identification with histopathological correlation is essential for appropriate management. We herein describe the clinical and histopathological characteristics of two cases of nipple adenoma.

Posttransplant lymphoproliferative disorder (PTLD) is a rare complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with poor prognosis. We report a patient with PTLD involved central nervous system (CNS) who treated with zanubrutinib, a second-generation Bruton tyrosine kinase (BTK) inhibitor. Our report supports the efficacy of bruton tyrosine kinase inhibitor zanubrutinib in the treatment of CNS-PTLD, which provides a new therapeutic option.

Hyperlipidemia, an important risk factor for cardiovascular and end-stage renal diseases, often aggravates renal injury and compromises kidney function. Here, histological analysis of human kidney samples revealed that high lipid levels induced the development of renal fibrosis. To elucidate the mechanism underlying lipid nephrotoxicity, we used two types of mouse models (Apoe−/− and C57BL/6 mice fed a 45 and 60% high-fat diet, respectively). Histological analysis of kidney tissues revealed high-lipid-induced renal fibrosis and inflammation; this was confirmed by examining fibrotic and inflammatory marker expression using Western blotting and real-time polymerase chain reaction. Oxidized low-density lipoprotein (OX-LDL) significantly induced the fibrotic response in HK-2 tubular epithelial cells. RNA-sequencing and Gene Ontology analysis of differentially expressed mRNAs in OX-LDL-treated HK-2 tubular epithelial cells and real-time PCR validation in Apoe−/− mice showed that the expression of thrombospondin-1 (THBS1) in the high-fat group was significantly higher than that of the other top known genes, along with significant overexpression of its receptor CD47. THBS1 knockdown cells verified its relation to OX-LDL-induced fibrosis and inflammation. Liquid chromatography tandem mass spectrometry and STRING functional protein association network analyses predicted that THBS1/CD47 modulated the interaction between γ-catenin and E-cadherin and was involved in epithelial–mesenchymal transition, which was supported by immunoprecipitation and immunohistochemistry. CD47 downregulation following transfection with small-hairpin RNA in OX-LDL-treated tubular epithelial cells and treatment with anti-CD47 antibody restored the expression of E-cadherin and attenuated renal injury, fibrosis, and inflammatory response in OX-LDL-treated cells and in type 2 diabetes mellitus. These findings indicate that CD47 may serve as a potential therapeutic target in long-term lipid-induced kidney injury.

Mitochondrial genomes (mitogenomes) are important for understanding molecular evolution and phylogenetic relationships. The complete mitogenome of Perisesarma bidens was determined, which is 15,641 bp in length. The A + T content of P. bidens mitogenome was 74.81%. The AT skew was slightly negative (−0.021). The 22 tRNAs ranged from 65 to 73 bp and were highly A + T biased. All tRNA genes had typical cloverleaf structures, except for the trnS1 gene, which lacked a dihydrouridine (DHU) arm. The gene order within the P. bidens mitogenome was identical to the pancrustacean ground pattern, except for the translocation of the trnH. Additionally, the gene order of trnI-trnQ-trnM in pancrustacean ground pattern became trnQ-trnI-trnM in P. bidens. Phylogenetic analyses supported the inclusion of P. bidens in Sesarmidae and the promotion of Sesarminae to Sesarmidae. The results will help us to better understand the status and evolutionary history of Grapsoidea crabs.

Gan-Mai-Da-Zao (GMDZ) is a well-known product in Chinese traditional medicine and includes three major plants: blighted wheat (Fu Mai), licorice (Gan Cao), and jujube (Da Zao). GMDZ is widely used as an efficacious and well-tolerated prescription for depression in clinics. The present study was designed to investigate the main plant of GMDZ for its antidepressant-like effect using the unpredictable chronic mild stress (UCMS) model on rats who received an injection with p-chlorophenylalanine (PCPA) to produce the chemical model. In rats subjected to the UCMS model, forced swim tests, open field tests, and sucrose preference tests were applied to estimate the chronic effect of GMDZ. We found that the oral administration of GMDZ for 21 days significantly alleviated the behavior in rats with depression induced by either UCMS or PCPA. The expression levels of the serotonin transporter (5-HTT) and brain-derived neurotrophic factor (BDNF) in the hippocampus of the rats with depression were markedly increased by GMDZ. Additionally, rats that received the herbal mixture without licorice showed a markedly lower response than GMDZ. These results suggest that GMDZ may alleviate the depressive-like behaviors in depressive rats, possibly via licorice (Gan Cao), to increase 5-HTT and BDNF signals in the hippocampus. The present study confirmed the antidepressant-like effects of GMDZ. Additionally, licorice (Gan Cao) may play a key role in the effectiveness of GMDZ.

Apathy is one of the common non-motor symptoms (NMS) in Parkinson's disease (PD), which can be defined as a syndrome of decreased motivation that manifests as a decrease in goal-directed behaviors. The mechanism of apathy in PD is undetermined, however, the mainstream opinion is that apathy is caused by prefrontal cortex-basal ganglia circuits damage. Prefrontal cortex-basal ganglia circuits damage in different regions lead to different subtypes of apathy, and the mechanism is associated with the anatomy and neurochemical of basal ganglia and related cortical regions. DOI: 10.3969/j.issn.1672-6731.2018.10.013

Abstract Background The pathogenesis of Kawasaki disease are still not well understood. It was designed to investigate the relationship between adipokines including chemerin, omentin-1, adiponectin and acute Kawasaki disease. Methods Enzyme-linked immunosorbent (ELISA) was used to detect serum levels of chemerin, omentin-1, adiponectin, and inflammatory cytokines IL-1β and TNF-α in 80 cases of patients diagnosed with Kawasaki disease (KD). In addition, 20 cases of children with fever and 20 cases of healthy children were selected as febrile and normal controls. Results (1) Serum levels of chemerin in KD group (87.736 ± 56.310) are higher than that of both the healthy (41.746 ± 10.824) and the febrile controls (59.683 ± 18.282) (P

The mitochondrial genome (mitogenome) provides important information for phylogenetic analysis and understanding evolutionary origins. Herein, we sequenced, annotated, and characterized the mitogenome of Metaplax longipes to better understand its molecular evolution and phylogeny. The 16,424 bp mitogenome includes 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, and one control region. The length of control region is 1036 bp. The nucleotide composition of M. longipes is A + T: 71.7%, with a strong AT bias. Phylogenetic analysis shows that M. longipes is closely related to Cyclograpsus granulosus and Helice wuana, which belong to the same family Varunidae.

Background: As a traditional Chinese medicine, Cordyceps sinensis (CS) possesses a variety of immunoregulatory properties. This study aimed to explore the therapeutic potential of CS in a mice model of multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE). Methods: Female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein35–55to induce EAE, followed by an instant intragastric feeding with a low dosage of CS (low-CS group, n = 5), high dosage of CS (high-CS group, n = 5), or the same volume of normal saline (control group, n = 5). All the mice were observed for clinical assessment. Over the 30 days of CS treatment, flow cytometry was used to detect the frequency of helper T-cell (Th) subsets, Th1 and Th17, and CD4+ CD25+ regulatory T cells in the spleen and lymph nodes. Meanwhile, pathological changes in brain were determined using both hematoxylin-eosin and luxol fast blue staining. Data were analyzed using the one-way analysis of variance (ANOVA). Results: Over the 15 and 30 days of CS treatment, the clinical assessment for EAE demonstrated that both high-CS group (2.51 ± 0.31 and 2.26 ± 0.39 scores, respectively) and low-CS group (2.99 ± 0.40 and 2.69 ± 0.46, respectively) had lower disease severity scores than those of control group (3.57 ± 0.53 and 3.29 ± 0.53, all P < 0.01, respectively). Meanwhile, after 15 and 30 days, the high-CS group (19.18 ± 1.34 g and 20.41 ± 1.56 g, respectively) and low-CS group (18.07 ± 1.18 g and 19.48 ± 1.69 g, respectively) had a lower body weight, as compared with control group (16.85 ± 1.15 g and 18.22 ± 1.63 g, all P < 0.01, respectively). At 30 days post-CS treatment, there was a lower Th1 frequency in the lymph nodes (2.85 ± 1.54% and 2.77 ± 1.07% vs. 5.35 ± 1.34%, respectively; P < 0.05) and spleens (3.96 ± 1.09% and 3.09 ± 0.84% vs. 5.07 ± 1.50%, respectively; P < 0.05) and less inflammatory infiltration and demyelination in the brain of CS-treated mice than that of control group. Conclusions: Our preliminary study demonstrated that CS efficiently alleviated EAE severity and EAE-related pathology damage and decreased the number of Th1s in the periphery, indicating its effectiveness in the treatment of murine EAE. Thus, our findings strongly support the therapeutic potential of this agent as a new traditional Chinese medicine approach in MS treatment.

Background To define benign intracerebral hemorrhage (ICH) and to investigate the association between benign ICH, hematoma expansion, and functional outcome. Methods and Results We analyzed a prospectively collected cohort of patients with ICH, who presented within 6 hours of symptom onset between July 2011 and February 2017 to a tertiary teaching hospital. Follow‐up computed tomographic scanning was performed within 36 hours after initial computed tomographic scanning. Benign ICH was operationally defined as homogeneous and regularly shaped small ICH. The presence of benign ICH was judged by 2 independent reviewers (Q.L., W.Y.) on the basis of the admission computed tomographic scan. Functional independence was defined as a modified Rankin Scale score of 0 to 2 at 3 months. The associations between benign ICH, hematoma expansion, and functional outcome were assessed by using multivariable logistic regression analyses. A total of 288 patients with ICH were included. Benign ICH was found in 48 patients (16.7%). None of the patients with benign ICH had early hematoma expansion. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of benign ICH for predicting functional independence at 3 months were 30.7%, 96.6%, 90.0%, 60.0%, and 0.637, respectively. Conclusions Patients with benign ICH are at low risk of hematoma expansion and poor outcome. These patients may be safe for less intensive monitoring and are unlikely to benefit from therapies aimed at preventing ICH expansion.

Background Previous studies showed that smoking is associated with increased multiple sclerosis (MS) susceptibility, while investigation of relation between smoking and risk of neuromyelitis optica spectrum disorders (NMOSDs) is rarely reported. Hence, this study aims to explore the association of smoking with MS and NMOSDs susceptibility and ascertain whether smoking can increase the risk of these two diseases. Methods Fifty-three MS patients, 62 NMOSDs patients and 85 healthy individuals were enrolled in this study. Standardized questionnaire or follow-up by telephone call were adopted to collect information regarding whether patients, healthy controls and their relatives have smoking behavior, and to learn circumstances of active smoking and passive smoking in these subjects. Results There were 156 subjects who finished effective questionnaires and telephone follow-up, including 39 MS patients, 43 NMOSDs patients and 74 controls. Compared with passive smoking and non-smoking subjects, the susceptibility of both MS (OR = 10.800, 95%CI: 2.202-52.975; P = 0.001) and NMOSDs (OR = 5.838, 95%CI: 1.123-30.357; P = 0.050) was significantly increased in active smoking subjects. Compared with non-smoking subjects, the susceptibility of both MS (OR = 3.444, 95% CI: 1.491-7.953; P = 0.003) and NMOSDs (OR = 2.370, 95%CI: 1.039-5.407; P = 0.038) was significantly increased in active and passive smoking subjects. In comparison with non-smoking males, smoking males were susceptible to MS (OR = 15.000, 95%CI: 2.239-100.483; P = 0.005). Conclusions Smoking is definitely the risk factor for MS, whereas it is not clear whether it is a risk factor for NMOSDs. DOI: 10.3969/j.issn.1672-6731.2016.09.009

Various methods for editing specific sites in the Escherichia coli chromosome are available, and gene-size (∼1 kb) integration into a single site or to introduce deletions, short insertions or point mutations into multiple sites can be conducted in a short period of time. However, a method for rapidly integrating multiple gene-size sequences into different sites has not been developed yet. Here, we describe a method and plasmid system that makes it possible to simultaneously insert genes into multiple specific loci of the E. coli genome without the need for chromosomal markers. The method uses a CRISPR-Cas12a system to eliminate unmodified cells by double-stranded DNA cleavage in conjunction with the phage-derived λ-Red recombinases to facilitate recombination between the chromosome and the donor DNA. We achieved the insertion of up to 3 heterologous genes in one round of recombination and selection. To demonstrate the practical application of this gene-insertion method, we constructed a recombinant E. coli producing an industrially useful chemical, 5-aminolevulinic acid (ALA), with high-yield. Moreover, a similar two-plasmid system was built to edit the genome of the extremophile Halomonas bluephagenesis.

Epidemiological studies suggest there is an association between midlife hypertension and increased risk of late-life Alzheimer’s disease (AD). However, whether hypertension accelerates the onset of AD or is a distinct disease that becomes more prevalent with age (comorbidity) remains unclear. This study aimed to test the possible relationship between hypertension and AD pathogenesis. Two animal models were used in this study. For the first model, 7-month-old Lanyu-miniature-pigs were given the abdominal aortic constriction operation to induce hypertension and their AD-related pathologies were assessed at 1, 2, and 3 months after the operation. The results showed that hypertension was detected since 1 month after the operation in the pigs. Levels of Aβ, amyloid precursor protein, RAGE, phosphorylated tau and activated GSK3β in the hippocampi increased at 3 months after the operation. For the second model, 3xTg mice at the ages of 2, 5, and 7 months were subjected to the “two-kidney-one-clip” operation to induce hypertension. One month after the operation, blood pressure was significantly increased in the 3xTg mice in any age. Aβ, amyloid plaque load, and phosphorylated tau levels increased in the operated mice. Furthermore, the operation also induced shrinkage in the dendritic arbor of hippocampal dentate gyrus granule neurons, leakage in the blood-brain barrier, activation in microglia, and impairment in the hippocampus-dependent learning and memory in the 3xTg mice. In conclusion, hypertension accelerates the onset of AD. Blood pressure control during midlife may delay the onset of AD.

Uca lactea is a crab belonging to the order Brachyura, but there is no report about its complete mitochondrial genome (mitogenome) in the literature. In this paper, the complete mitogenome of U. lactea was sequenced and the phylogenetic relationship was analyzed based on nucleotide sequences of the 13 protein-coding genes (PCGs) using the maximum likelihood (ML) method. The complete mitogenome of U. lactea is 15,659 bp (GenBank accession No. KY865330) in length and contains 22 tRNA genes, 13 protein-coding genes (PCGs), 2 rRNA genes, and a D-loop region. All PCGs were initiated by ATN codons. The nucleotide composition was also biased toward A + T nucleotides (69.48%). Phylogenetic analysis showed that U. lactea can be placed within the family Ocypodidae. This mitogenome sequence will provide a better understanding for crab evolution in the future.

The existing attribute-based encryption access control studies are mostly based on single authority,and this scheme is apt to be under attack to cause exposure of secret keys.Thus,a multi-authority access control model PRM-CSAC is proposed.Based on CP-ABE method,a multi-authority attribute-based encryption scheme is designed to improve security level.Minimized attribute grouping algorithm is designed to distribute keys to users according to needs,which can reduce unnecessary attribute key distribution and decrease the amount of re-encryption attributes.The read and write attribute are added to strengthen the control of owners.The analysis shows that the proposed scheme can meet the security requirement of access control in cloud,and it also has less response time and system cost.

Objective To investigate the clinical features of multiple sclerosis (MS) patients with positive serum aquaporin 4 (AQP4) antibody. Methods A total of 18 MS patients who had been diagnosed in accord with McDonald Criteria (2010) were enrolled and were divided into AQP4 positive group (N = 5) and AQP4 negative group (N = 13). In combination with accessory examination, clinical features and laboratory data of MS patients were correlatively studied between 2 groups in association with follow-up study in Outpatient Clinic. Results Five seropositive patients, including 2 men and 3 women, were collected. The median age of onset was 43 years and the median clinical course was 4 months. Compared with patients with negative AQP4 antibody, MS patients with positive AQP4 antibody demonstrated increased spinal cord lesions and optic nerve involvement. MRI revealed multiple abnormal long T1 and long T2 signals in brain and cervicothoracic spinal cord (3/5), and multiple abnormal long T1 and long T2 signals in cervicothoracic spinal cord (2/5) in seropositive group. Relatively more patients in seropositive group had increased cerebral spinal fluid (CSF) IgG index (4/4) and 24 h intrathecal IgG synthesis rate (3/4), and positive oligoclonal bands (OBs, 3/4). Two patients presented with positive anti-nuclear antibody (ANA) and one Sjögren's syndrome (SS) in seropositive group. Conclusions There were some differences in clinical features between AQP4 antibody positive MS and classical MS, suggesting distinctive pathogenesis may exist between these two entities, which need to be emphasized and treated accordingly from the diagnostic and therapeutic points of view. HE Yang and YANG Ting-ting contributed equally to this studyDOI: 10.3969/j.issn.1672-6731.2015.03.012