A Novel Frameshift Mutation(HBA2:C.337delC) Associated With α-Thalassemia Trait Detected by Next-Generation Sequencing in Southern China.

Here, we report a novel frameshift mutation caused by a single base deletion in exon 3 of the HBA2 gene (HBA2:c.337delC) detected by next-generation sequencing. The proband was a 26-year-old Chinese pregnant woman who originates from Hunan Province. Her mean corpuscular volume(MCV) and mean corpuscular hemoglobin (MCH) had a mild decrease. Capillary electrophoresis (CE) showed that both Hb A (97.8%) and Hb F (0.0%) values were within normal range, while the Hb A2 (2.2%) value was below normal. Sequence analysis of the α and ß-globin genes revealed a novel single base deletion at codon 112 (HBA2:c.337delC) in the heterozygous state, which resulted in a mild phenotype of α-thalassemia.

Jiawei Shengmai San herbal formula ameliorates diabetic associate cognitive decline by modulating AKT and CREB in rats.

Memory loss is a complication of diabetes which requires new approaches to its treatment. Shengmai San (SMS) is a famous traditional Chinese formula containing Panax ginseng, Ophiopogon japonicas, and Schisandra chinensis, whereas Radix puerariae has many reported pharmacological uses. In this study the combination, as Jiawei SMS (J-SMS) was screened for its ability to reverse diabetes-associated cognitive decline in rats. This was assessed behaviorally in diabetic rats (Streptozotocin, 45 mg/kg), with biochemical and western blot analysis (Akt and CREB). Diabetic rats showed fasting blood glucose (FBG) in the range of 13-15 mM throughout the study. J-SMS (0.5, 1.5, 4.5 g/kg) treatment significantly improved learning and memory deficit among diabetic rats as evidenced by preference for novel object, reduced escape latency and increased number of platform crossings (p < .05) in the NORT and MWM tests. Treatment with J-SMS also significantly improved the histopathological changes in the diabetic brain and increased the protein expression of AKT and CREB, required for proper memory function (p < .01). This study highlighted that J-SMS can reverse reference and working memory deficit among diabetic rats by modulating AKT and CREB proteins activation. Thus, J-SMS formulation might be possible candidate for further development.

Time-dependent impairments in learning and memory in Streptozotocin-induced hyperglycemic rats.

The sedentary lifestyle is responsible for the high prevalence of diabetes which also impairs cognition including learning and memory. Various studies have highlighted the learning and memory impairments in rodent models but data regarding the timeline of their development and their correlation to biochemical parameters are scarce. So, the present study was designed to investigate the type of memory which is more susceptible to hyperglycemia and its correlation with biochemical parameters such as inflammatory cytokines, cAMP response element binding (CREB) and protein kinase B (Akt) activation. Hyperglycemia was induced using streptozotocin (STZ, 45 mg/kg i.p.) and confirmed by measuring fasting blood glucose levels after 1 week of STZ injection. Learning and memory deficits were evaluated using the Novel Object Recognition Test (NORT) and Morris water maze (MWM), and correlated with biochemical parameters (TNF-α, IL-1ß, and dopamine) at 3, 6 and 9 weeks. STZ-injected rats after 3 weeks of injection demonstrated moderate hyperglycemia (blood glucose = 7.99 ± 0.62 mM) with intact learning and reference memory; however, their working memory was impaired in MWM. Severe hyperglycemia (blood glucose = 11.51 ± 0.69 mM) accompanied by impaired short, long, and working memory was evident after 6 weeks whereas learning was intact. After 9 weeks of STZ injection, hyperglycemia was more pronounced (13.69 ± 1.43 mM) and accompanied by a learning deficit in addition to short, long, and working memory impairments. The extent of hyperglycemia either in terms of duration or severity resulted in enhanced inflammation, down-regulation of the level of dopamine, protein expression of AKT and CREB, which possibly affected learning and memory negatively.

Expression, purification and characterization of the full-length SmpB protein from Mycobacterium tuberculosis.

The trans-translation system is recognized as an excellent target for developing new drugs to rapidly sterilize Mycobacterium tuberculosis (TB) infection and significantly shorten TB treatment duration. As a vital component of the trans-translation system for rescuing stalled ribosomes, the SmpB protein from Mycobacterium tuberculosis (MtbSmpB, 1-160 a. a.) mediates tmRNA binding to stalled ribosomes through forming a complex with tmRNA. So far, few works have been conducted to prepare, characterize biophysical properties and determine three-dimensional structure for the full-length MtbSmpB protein. In the present work, we successfully expressed and purified the His-tagged full-length MtbSmpB protein in Escherichia coli with a yield of 26.9 mg from 1 L of Luria Bertani medium. We also obtained MtbSmpB with a yield of 18.5 mg from 1 L of M9 minimal medium. The MtbSmpB protein showed a single band in SDS-PAGE with a molecular weight of ∼20 kDa consistent with the measurement from MALDI-TOF-mass spectrometry. The dynamic light scattering experiment indicated that MtbSmpB existed in a monomeric form. Moreover, both circular dichroism and nuclear magnetic resonance (NMR) experiments exhibited that MtbSmpB was well structured, suggesting that it could be feasible to determine its solution structure by NMR spectroscopy. NMR titration experiments showed that MtbSmpB specifically bound to tmRNA. This work lays the essential basis for further determining the solution structure and dynamics of the full-length MtbSmpB protein.

A novel NHS mutation causes Nance-Horan Syndrome in a Chinese family.

BACKGROUND: Nance-Horan Syndrome (NHS) (OMIM: 302350) is a rare X-linked developmental disorder characterized by bilateral congenital cataracts, with occasional dental anomalies, characteristic dysmorphic features, brachymetacarpia and mental retardation. Carrier females exhibit similar manifestations that are less severe than in affected males. METHODS: Here, we report a four-generation Chinese family with multiple affected individuals presenting Nance-Horan Syndrome. Whole-exome sequencing combined with RT-PCR and Sanger sequencing was used to search for a genetic cause underlying the disease phenotype. RESULTS: Whole-exome sequencing identified in all affected individuals of the family a novel donor splicing site mutation (NM_198270: c.1045 + 2T > A) in intron 4 of the gene NHS, which maps to chromosome Xp22.13. The identified mutation results in an RNA processing defect causing a 416-nucleotide addition to exon 4 of the mRNA transcript, likely producing a truncated NHS protein. CONCLUSIONS: The donor splicing site mutation NM_198270: c.1045 + 2T > A of the NHS gene is the causative mutation in this Nance-Horan Syndrome family. This research broadens the spectrum of NHS gene mutations, contributing to our understanding of the molecular genetics of NHS.

[Antidepressant effects of the extract of Dendrobium nobile Lindl on chronic unpredictable mild stress-induced depressive mice].

To investigate whether the extract of Dendrobium nobile Lindl (DNL) has an antidepressant effect on chronic unpredictable mild stress (CUMS)-induced depressive mice, 72 BALB/c male mice were randomly divided into the control group, the CUMS model group, the extract of DNL groups (50, 100 and 200 mg/kg DNL, i.g.) and the paroxetine group (10 mg/kg, i.g.). The different doses of DNL or the paroxetine was administered orally once daily to CUMS mice for 8 weeks (containing two-week preventive medication before the modeling). The same volume of distilled water was given to the control group and the CUMS group. Except for the control group, the other mice were exposed to chronic stress for 35 days. Behavioral tests were performed by using the sucrose preference test (SPT), the novelty-suppressed feeding (NSF) test, the tail suspension test (TST), and the forced swim test (FST). The levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) were measured by the liquid chromatography-mass spectrometer (LC-MS)/MS. Compared with the control group, obvious behavioral changes were observed in the CUMS group after 5-week CUMS, including a decrease in the sucrose consumption, an increase in the latency to feeding in the NSF test and a prolongation of the immobility time in the TST. Compared with the CUMS group, the application of DNL resulted in a dose-dependent increase in sucrose consumption (P < 0.01) as paroxetine (10 mg/kg) did and a significant dose-dependent decrease in the latency to feeding in the NSF test (P < 0.05). In the TST, the application of paroxetine (10 mg/kg) and the high-dose DNL (200 mg/kg) obviously decreased the immobility time when compared with the CUMS group (P < 0.05). In the FST, compared with the CUMS group, all the groups had no significant differences in the immobility time (P > 0.05). In addition, in the hippocampus and cortex, the levels of 5-HT and DA were significantly decreased in the CUMS group compared with the control group (P < 0.05). In comparison with the CUMS group, paroxetine obviously increased the DA levels in the hippocampus and the cortex and the 5-HT level in the hippocampus (P < 0.05). DNL (50 and 200 mg/kg) significantly increased the DA level in cerebral cortex of the brain, and DNL (100 and 200 mg/kg) increased the DA level in the hippocampus. The 5-HT level in the 200 mg/kg DNL group was notably increased in both two brain regions (P < 0.05), but the 5-HT level in the 100 mg/kg DNL group was significantly increased only in the hippocampus (P < 0.01). These findings indicate that the extract of DNL has an antidepressant-like effect on CUMS-induced depressive mice and its mechanism may be related to the changes in DA and 5-HT in the hippocampus and cortex.

Development of a conjugate vaccine against invasive pneumococcal disease based on capsular polysaccharides coupled with PspA/family 1 protein of Streptococcus pneumoniae.

The efforts were focused on exploring alternative pneumococcal vaccine strategies, aimed at addressing the shortcomings of existing formulations, without compromising efficacy. Our strategy involved the use of the carrier protein, pneumococcal surface protein A (PspA), conjugated with capsular polysaccharides (CPS), to provide effective and non-serotype-dependent protection. In this study, we generated a stable Escherichia coli construct expressing functional PspA from a capsular serotype 6B strain and confirmed it belonging to family 1, which was conjugated with CPS. The distribution of anti-CPS antibody response was almost completely of IgG2a subclass followed by IgG3 and low level of IgG1 subclass, but that of anti-PspA IgG subclass antibodies was almost equal IgG1 and IgG2a subclasses. Though PspA was less conspicuous on the surface of pneumococci than the capsule, the antibodies induced with CPS-rPspA conjugate possessed more accessibility to the surface of Streptococcus pneumoniae serotype 6B and 19F (the same family 1 PspA). By survival experiment, the result suggested that the level of cross-protection after immunized with the conjugate was more measurable within the same family 1. The CPS-rPspA conjugate not only induced CPS-specific protection but also provided PspA specific cross-protection.

Primer-introduced restriction analysis polymerase chain reaction method for non-invasive prenatal testing of ß-thalassemia.

We have developed a new method for non-invasive prenatal testing (NIPT) of paternally inherited fetal mutants for ß-thalassemia (ß-thal). Specially designed primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) were used to detect four major mutations [IVS-II-654, HBB: c.316-197C > T; codon 17 (A > T), HBB: c.52A > T; -28 (A > G), HBB: c.-78A > G and codons 41/42 (-TTCT), HBB: c.126_129delCTTT] causing ß-thal in China. The PIRA-PCR assay was first tested in a series of mixed DNA with different concentrations and mixed proportions. Subsequently, this assay was further tested in 10 plasma DNA samples collected from pregnant women. In the DNA mixture simulation test, the PIRA-PCR assay was able to detect 3.0% target genomic DNA (gDNA) mixed in 97.0% wild-type gDNA isolated from whole blood. For plasma DNA testing, the results detected by PIRA-PCR assay achieved 100.0% consistency with those obtained from the amniocentesis analysis. This new method could potentially be used for NIPT of paternally inherited fetal mutants for ß-thal.

Clinical effect evaluation of percutaneous vertebroplasty combined with the spinal external fixator for the treatment of osteoporotic compressive fractures with posterior vertebral defect.

PURPOSE: The purpose of this study is to report a new technique and assess clinical outcome of compressive fractures with posterior vertebral defect treated by percutaneous vertebroplasty combined with the spinal external fixator. METHOD: 80 patients (32 males and 48 females), ranging from 62 to 88 years old with the mean age of 71.5 years, underwent surgery for the compressive fractures with posterior vertebral defect by percutaneous vertebroplasty combined with the spinal external fixator. All patients were diagnosed to have fresh compressive fractures with osteoporosis and posterior vertebral defect shown on roentgenograms, computed tomography scans or magnetic resonance imaging preoperatively. They underwent spinal external fixation firstly to be fixed and restored, then to be carried out percutaneous vertebroplasty. The mean follow-up was 24 months (16-42 months). Spinal canal encroachment, spinal cobb angle and vertebral body height loss were measured to assess clinical outcome before and after surgery, at the final follow-up. The Visual Analogue Scale and Oswestry Disability Index were used for pain and functional assessment. In all cases, preoperative and postoperative radiographs and magnetic resonance imaging were obtained. RESULTS: The average time of surgery was 88 min (75-115 min). The mean blood loss was 10 ml (6-12 ml) during surgery. The anterior height loss of vertebral body decreased significantly from 79.3 ± 11% before surgery to 8.0 ± 5.2% after surgery, and 7.6 ± 6.0% at the final follow-up. The spinal canal encroachment significantly reduced from 19.9 ± 2.6 % preoperatively to 4.0 ± 0.7% postoperatively, 4.1 ± 0.7% at the final follow-up. The Cobb angle was corrected from 25.8 ± 7.9° primarily to 8.2 ± 4.1° postoperatively, 7.8 ± 3.1° at the final follow-up. There were significant differences (p < 0.05) among them before and after the surgery. Postoperative VAS and Oswestry scores were both significantly different from the preoperative and follow-up (p < 0.05). CONCLUSION: The preliminary results are encouraging, showing that the spinal external fixator combined with percutaneous vertebroplasty was a safe and effective method to treat the osteoporotic compressive fractures with posterior vertebral defect.

The impact of rural e-commerce participation on farmers' entrepreneurial behavior: Evidence based on CFPS data in China.

The "Three Rural Issues", encompass challenges related to agriculture, farmer, and rural area, which hold significant importance in driving comprehensive rural revitalization efforts in China. Farmer entrepreneurship, as a crucial means to enhance productivity, create job opportunities, and increase residents' income, has gradually become a key driving force in promoting rural revitalization in the new stage of development in China. With the rapid development of rural e-commerce, farmer entrepreneurship has encountered new opportunities. This study utilizes the 2020 China Family Panel Studies (CFPS) data and employs a structural equation model (SEM) to analyze the direct impact of rural e-commerce participation on farmer entrepreneurial behavior, considering factors such as human capital, social capital, and network infrastructure. This study further explores the indirect effects and mechanisms of e-commerce participation as a mediating variable and analyzes the impact and mechanisms on agricultural entrepreneurship behavior. The findings are as follows: (1) E-commerce participation significantly promotes farmer entrepreneurial behavior; (2) E-commerce participation as a mediating variable has a positive indirect effect on the relationship between social trust, network infrastructure, human capital, and farmer entrepreneurial behavior; (3) E-commerce participation has a significant positive influence on farmer entrepreneurship in the agricultural sector, and farmers with higher levels of network infrastructure and human capital have a higher probability of choosing agricultural entrepreneurship under the influence of e-commerce participation. Finally, this study provides policy recommendations in terms of infrastructure construction, entrepreneurial policy environment, and education level, aiming to optimize the situation of farmer entrepreneurship and contribute to the comprehensive promotion of rural revitalization.Overall, the research in this paper effectively combines theory and empirical evidence to outline the direct and indirect impact mechanisms of rural e-commerce participation on farmers' entrepreneurial behavior and agriculture-related entrepreneurial behavior and to test the effects of their impacts. First, most of the existing literature deals with farmers in individual sample areas, while the sample selected in this paper is farmers in the whole country, which is relatively more generalizable; second, most of the previous studies explore the level of e-commerce in the inter-provincial or county areas, while this paper expands the empirical study of rural e-commerce on the entrepreneurial behavior of farmers and the micro-period of agricultural entrepreneurial behavior, and focuses on the impacts of the e-commerce activities of farmers on their entrepreneurial behavior.

The adsorption and release mechanism of different aged microplastics toward Hg(II) via batch experiment and the deep learning method.

Aged microplastics are ubiquitous in the aquatic environment, which inevitably accumulate metals, and then alter their migration. Whereas, the synergistic behavior and effect of microplastics and Hg(II) were rarely reported. In this context, the adsorptive behavior of Hg(II) by pristine/aged microplastics involving polystyrene, polyethylene, polylactic acid, and tire microplastics were investigated via kinetic (pseudo-first and second-order dynamics, the internal diffusion model), Langmuir, and Freundlich isothermal models; the adsorption and desorption behavior was also explored under different conditions. Microplastics aged by ozone exhibited a rougher surface attached with abundant oxygen-containing groups to enhance hydrophilicity and negative surface charge, those promoted adsorption capacity of 4-20 times increment compared with the pristine microplastics. The process (except for aged tire microplastics) was dominated by a monolayer chemical reaction, which was significantly impacted by pH, salinity, fulvic acid, and co-existing ions. Furthermore, the adsorbed Hg(II) could be effectively eluted in 0.04% HCl, simulated gastric liquids, and seawater with a maximum desorption amount of 23.26 mg/g. An artificial neural network model was used to predict the performance of microplastics in complex media and accurately capture the main influencing factors and their contributions. This finding revealed that aged microplastics had the affinity to trap Hg(II) from freshwater, whereafter it released the Hg(II) once transported into the acidic medium, the organism's gastrointestinal system, or the estuary area. These indicated that aged microplastics could be the sink or the source of Hg(II) depending on the surrounding environment, meaning that aged microplastics could be the vital carrier to Hg(II).

A novel therapeutic strategy of combined camrelizumab and apatinib for the treatment of advanced hepatocellular carcinoma.

Methods: 83 patients with hepatocellular carcinoma (HCC) admitted to the interventional oncology department were randomly divided into two groups. Apatinib and camrelizumab were administered to 42 patients in group A, whereas sorafenib was administered to 41 patients in group B for three months. The clinical efficacy was evaluated in terms of objective response rate (ORR), and disease control rate (DCR). Certain tumor markers like alpha-fetoprotein (AFP), carbohydrate antigen 199 (CA199), carcinoembryonic antigen (CEA), hypoxia-inducible factor (HIF-1), immune function T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+) were determined before and after treatment. The serum levels of vascular endothelial growth factor (VEGF), osteopontin (OPN), aspartate aminotransferase (AST), and epidermal growth factor 7 (EGF7)] were observed. The survival time between the two groups was compared, such as progression-free survival (PFS) and median survival (MS). Finally, the toxicity and side effects data were also obtained. Results: The ORR and DCR of group A were 69.05% and 88.10%, respectively, which were significantly higher (P<0.05) than group B (ORR=53.66% and DCR=70.73%). After treatment, the AFP, CA199, CEA, and HIF-1 levels of both groups decreased significantly (P<0.05), and the respective biomarker levels of group A were lower than those of group B (P<0.05). Following treatment, CD3+, CD4+, CD4+/CD8+ index in group A significantly increased (P<0.05) while CD8+ level was significantly decreased (P<0.05). Compared to group B, a significant increase was observed in group A's CD3+, CD4+, and CD4+/CD8+ index. There were no significant changes in CD3+, CD4+, CD8+, CD4+/CD8+ indexes before and after treatment in group B (P>0.05). The serum level of VEGF, OPN, EGF-7 and AST indexes of group A&B were decreased significantly (P<0.05). Compared with group B, the VEGF, OPN, EGF7 and AST indexes of group A were significantly reduced (P<0.05). PFS and MS in group A were significantly higher than in group B (P<0.05). There was no significant difference between groups A and B in terms of toxicity and adverse effects (P>0.05). Conclusion: In treating HCC, combining apatinib and camrelizumab can reduce tumor markers, enhance the immune system and curative effect, and prolong patient survival. The underline mechanism is related to the down-regulation of VEGF, OPN and HIF-1 indexes.

One-step synthesis of thiol-functionalized metal coordination polymers: effective and superfast removal of Hg (II) in the different matrices to ppb level.

The mercury in water bodies has posed a great threat to the environment and humans, and removing mercury and purifying wastewater has become a global environmental issue. Adopting Zn(II) coordination polymers (Zn-CPs) emerged as a new approach, however, the kind of Zn-CPs, which solely consisted of amino groups, exhibited unsatisfactory performance in capturing Hg(II) at a low level and causing the subsequent leaching of Zn(II) after adsorption. In this study, we fabricated the thiol-modified Zn-based coordination polymers (Zn-CPs-SH) through a one-step solvothermal reaction to efficiently capture Hg(II) from wastewater. Its preeminent adsorption performance could be maintained across a broad range of pH (2-7), ion strength (Cl-, SO42-, and NO3- at 0-10,000 mg/L), and dissolved organic matter (0-100 mg/L). The impressive properties, including fast kinetics (k2∼1.01 × 10-4 L/min), outstanding adsorption capacity (1278.72 mg/g, 298 K), superior selectivity (Kd∼2.3 × 104 mL/g), and excellent regeneration capability (Re = 93.54% after 5 cycles), were attributed to the ultra-abundance of adsorption sites donating from thiol groups, which was revealed by XPS analysis, DFT calculations, and molecular orbital theory. Noteworthy, the high practical application potential of Zn-CPs-SH was demonstrated by its outstanding Hg(II) removal efficiency (Re ≥ 99.10%) in various Hg(II)-spiked water matrices, e.g., tap water, river water, and industrial wastewater. Importantly, the residual Hg(II) in the treated water declined to the ppb level without any Zn(II) leaching. Overall, it is highly anticipated that the incorporation of Zn-CPs-SH would facilitate the practical implementation of highly efficient Hg(II) removal in wastewater treatment owing to its exhibiting high selective affinity, superior adsorption capacity, and enhanced efficiency.

Inter- and intra-rater agreement of interpretation of functional lumen imaging probe in healthy subjects.

BACKGROUND: The functional lumen imaging probe (FLIP) evaluates esophagogastric junction (EGJ) opening and esophageal contractility. Both post hoc and real-time analyses are possible, but reproducibility and reliability of analysis remain undefined. This study assesses inter- and intra-rater agreement of normative FLIP measurements among novice and experienced users. METHODS: Eight motility experts from different institutions independently evaluated de-identified video recordings from 27 asymptomatic healthy subjects using FLIP. Interpretation methods simulating a post-procedure and a live procedure setting were tested. Novice FLIP users (n = 3) received training prior to post-procedure interpretation. Experienced FLIP users (n = 5) interpreted using both methods. Users recorded maximum EGJ and distal esophageal body diameter, distensive pressure, and EGJ distensibility index (EGJ-DI), at balloon fill volumes of 50-, 60-, and 70 ml, as well as repetitive antegrade contractions (RACs). Inter- and intra-rater agreements of diameters, distensive pressure and EGJ-DI were assessed by intra-class correlation coefficient (ICC) and Pearson's correlation coefficient (PCC). Percentage agreement evaluated inter- and intra-rater reliability for RACs. KEY RESULTS: Novice and experienced users acquired normative FLIP metrics. Good-to-excellent inter- and intra-rater reliability were achieved for all variables at 60 ml balloon fill volumes. Median parameters at 60 ml balloon fill volume were as follows: EGJ-DI 5.5 mm2 /mmHg, maximum EGJ diameter 18.6 mm, distensive pressure at maximum EGJ diameter 48.1 mmHg, and distal esophageal body diameter 19.5 mm. CONCLUSIONS AND INFERENCES: Normative FLIP parameters can be reliably extracted from FLIP videos using both real-time and post hoc analyses, with high reliability between experienced and novice users.

Degradation of 1-(2-chlorobenzoyl)-3-(4-chlorophenyl) urea by nanoscale zerovalent iron under aerobic and anaerobic conditions.

The goal of present study was to investigate the applicability of nanoscale zerovalent iron (NZVI) on the degradation of 1-(2-chlorobenzoyl)-3-(4-chlorophenyl) urea (CCU) under aerobic and anaerobic conditions, respectively. The experimental results showed that NZVI could effectively degrade CCU, but the removal efficiencies were different under these two different conditions. The best removal efficiencies for CCU were 90.2 and 75.8% under aerobic and anaerobic conditions, respectively. The highly oxidative hydroxyl radicals and reductively hydrogen would account for the rapid degradation of CCU under aerobic and anaerobic conditions, respectively. The experimental results also showed that surfactant Tween 20 significantly inhibited the degradation of CCU under aerobic conditions. However it markedly enhanced the degradation of CCU under anaerobic condition.

Normative values for esophageal functional lumen imaging probe measurements: A meta-analysis.

BACKGROUND: The functional lumen imaging probe (Endoflip™) is increasingly used for evaluation of patients with esophageal symptoms. To improve the interpretation of Endoflip™ in clinical practice, normative values with appropriate cut-off values are required. METHODS: Original clinical studies describing Endoflip™ use for measurements of esophageal motility in healthy adults were considered. Meta-analysis was performed based on published values. RESULTS: A total of 17 articles were included in the systematic review, 15 of which were included in the meta-analysis, representing 154 unique subjects. At 40 ml distention, the 5th-95th and 10th-90th percentiles for esophagogastric junction distensibility index (EGJ-DI) were 1.96-10.95 mm2 /mmHg and 2.36-8.95 mm2 /mmHg, respectively. An EGJ-DI below 2 mm2 /mmHg was found in 5.4%, and below 3 mm2 /mmHg in 20.1% of healthy subjects. At 50 ml distention, the 5th-95th and 10th-90th percentiles for EGJ-DI are 2.86-10.66 mm2 /mmHg and 3.28-9.12 mm2 /mmHg, respectively (below 2 mm2 /mmHg: 0.6%, 3 mm2 /mmHg: 6.3%). The 5th-95th and 10th-90th percentiles for EGJ-DI at 60 ml distention were 3.06-8.14 mm2 /mmHg and 3.33-7.18 mm2 /mmHg, respectively (below 2 mm2 /mmHg: 0.0%, 3 mm2 /mmHg: 7%). A clear cut-off for lower values was identified while a large spread in values was observed for upper limits of normal for EGJ-DI for all filling volumes. CONCLUSIONS: Given these observations, we recommend using a cut-off of 2 mm2 /mmHg for clinical practice, values below can be considered abnormal. Given that 5.4% of the healthy subjects will have an EGJ-DI below 2 mm2 /mmHg at 40 ml, we recommend using the 50 and 60 ml distention volumes. The clinical use of an upper limit for normality of EGJ-DI seems questionable.

Influence of Social Support Network and Perceived Social Support on the Subjective Wellbeing of Mothers of Children With Autism Spectrum Disorder.

This study explored the relations between the social support network of mothers of children with autism spectrum disorder (ASD), perceived social support, and their subjective wellbeing. The participants were mothers of children with ASD in Shanghai. Their social support network structure was explored via the nomination method. Perceived social support was measured using the Revised Social Provisions Scale for Autism (R-SPS-A), and the mothers' subjective wellbeing was assessed using the Index of Wellbeing, Index of General Affect. A significant correlation was observed between the subjective wellbeing of mothers of children with ASD and perceived social support. Meanwhile, perceived social support was significantly correlated with the effectiveness of overall social support. Finally, perceived social support was also significantly correlated with the network size of social support. Moreover, the effectiveness of social support was significantly associated with the network size of social support and was highly significantly associated with the degree of intimacy of social support. Furthermore, the network size of instrumental support has a significant influence on all perceived social support subdimensions. Overall, social support effectiveness plays an important role in the social support network mechanism on perceived social support and subjective wellbeing in China.

Influence of Rural Social Capital and Production Mode on the Subjective Well-Being of Farmers and Herdsmen: Empirical Discovery on Farmers and Herdsmen in Inner Mongolia.

Rural areas are crucial to the realization of sustainable development goals (SDGs). Rural social capital is indispensable for these areas to fulfil the SDGs. As China pursues rural revitalization, it is essential to achieve the sustainable development of rural areas within the agropastoral transition zone (APTZ) in northern China. The same applies to the SDGs' realization in other APTZs across the globe. From the micro perspective of individual farmers and herdsmen, this article collected 732 microscopic datapoints through repeated rural surveys, and adopted the multivariate ordered probit model to empirically analyze how the subjective well-being of farmers and herdsmen in northern China's APTZ was affected by the individual (person) and collective (community) layers of rural social capital. Specifically, the production mode was introduced to study the relationship between social capital and subjective well-being, and social capital was measured by a self-designed theoretical analysis framework, which covered six dimensions and two layers (person and community). It was verified that the individual social capital and collective social capital were mutually replaceable in terms of the effect on the subjective well-being of farmers and herdsmen. Additionally, this article examined the influence of different production modes on the social capital and subjective well-being of farmers and herdsmen, and discussed how the same amount of social capital contributes differently to the subjective well-being of farmers and herdsmen under different production models. The results showed that: (1) Social capital significantly promoted the subjective well-being of farmers and herdsmen, and social network was the leading contributor among the dimensions of individual social capital, while social trust was the leading contributor among the dimensions of collective social capital. By the contribution to the subjective well-being of farmers and herdsmen, the six dimensions of social capital can be ranked as social network > social trust > social participation > social standard > social fame > common vision. (2) Individual social capital and collective social capital were mutually replaceable in terms of enhancing the subjective well-being of farmers and herdsmen; when the individual social capital was insufficient, the collective social capital would exert a much greater influence on the subjective well-being of farmers and herdsmen; when the individual social capital grows, the farmers and herdsmen would depend less on collective social capital. (3) The same amount of social capital contributes differently to the subjective well-being of farmers and herdsmen under different production models; by contribution strength, the production models can be ranked as pure herdsmen (PH) > pure farmers (PF) > non-farmers/herdsmen (NFH) > farmers + herdsmen (FH). Finally, several policy suggestions were provided to improve the subjective well-being of farmers and herdsmen in APTZ. The results show that collective social capital eliminates the negative effect of individual social capital shortage on the subjective well-being of farmers and herdsmen. Thus, it is suggested to consider not only the construction of macroscopic hardware environment, but also to roll out policies and measures to improve the subjective well-being from the micro perspective of farmers and herdsmen. These suggestions are concentrated on the implementation of China's rural revitalization strategy, and the creation of relevant institutions and cultural environments, as well as the optimization of the internal hierarchy of farmers and herdsmen's social capital. The research results may help to promote the subjective well-being of farmers and herdsmen in rural areas within the APTZs of China and the world, and provide a reference and a path to realize SDGs in China and similar places across the globe.

[Expression, purification, and characterization of cell-permeable fusion antioxidant enzyme sensitive to matrix metalloproteinases-2/9].

Antioxidant enzymes fused with cell-penetrating peptides could enter cells and protect cells from irradiation damage. However, the unselective transmembrane ability of cell-penetrating peptide may also bring antioxidant enzymes into tumor cells, thus protecting tumor cells and consequently reducing the efficacy of radiotherapy. There are active matrix metalloproteinase (MMP)-2 or MMP-9 in most tumor cellular microenvironments. Therefore, a fusion protein containing an MMP-2/9 cleavable substrate peptide X, a cell-penetrating peptide R9, a glutathione S-transferase (GST), and a human Cu, Zn superoxide dismutase (SOD1), was designed and named GST-SOD1-X-R9. In the tumor microenvironment, GST-SOD1-X-R9 would lose its cell-penetrating peptide and could not enter tumor cells due to the cleavage of substrate X by active MMP-2/9, thereby achieving selected entering normal cells. The complete nucleotide sequence of SOD1-X-R9 was synthesized and inserted into the prokaryotic expression vector pGEX-4T-1. The pGEX4T-1-SOD1-X-R9 recombinant plasmid was obtained, and soluble expression of the fusion protein was achieved. GST-SOD1-X-R9 was purified by ammonium sulfate precipitation and GST affinity chromatography. The molecular weight of the fusion protein was approximately 47 kDa, consistent with the theoretical value. The SOD and GST activities were 2 954 U/mg and 328 U/mg, respectively. Stability test suggested that almost no change in either SOD activity or GST activity of GST-SOD1-X-R9 was observed under physiological conditions. The fusion protein could be partially digested by collagenase Ⅳ in solution. Subsequently, the effect of MMP-2/9 activity on transmembrane ability of the fusion protein was tested using 2D and 3D cultured HepG2 cells. Little extracellular MMP-2 activity of HepG2 cells was observed under 2D culture condition. While under the 3D culture model, the size and the MMP-2 activity of the HepG2 tumor spheroid increased daily. GST-SOD1-R9 proteins showed the same transmembrane efficiency in 2D cultured HepG2 cells, but the transmembrane efficiency of GST-SOD1-X-R9 in 3D cultured HepG2 spheres was reduced remarkably. This study provided a basis for further investigating the selectively protective effect of GST-SOD1-X-R9 against oxidative damage in normal cells.

Measurement and identification of relative poverty level of pastoral areas: an analysis based on spatial layout.

Pastoral areas are the key difficulty in China's pursuit of common prosperity and a key region for China to build the northern ecological safety barrier and to realize the Two Centenary Goals. It is of great significance to scientifically evaluate the quality of rural life (QRL), measure the relative poverty level (RPL), and identify the relatively poor areas, making it possible to dock poverty elimination with rural revitalization. Based on the socio-economic data of 18 pastoral areas in Inner Mongolia, this paper draws on spatial layout theory to evaluate QRL and measures RPL by the natural breakpoint method and then identifies the relatively poor areas in Inner Mongolia. The results show that (1) the QRLs of pastoral areas in Inner Mongolia were unbalanced and highly polarized. The mean score of QRLs was 0.2598. Eleven (61.11%) of the counties/banners had a QRL smaller than the mean score. On the spatial layout of QRLs, the western areas were stronger than the central areas. High QRL counties/banners are mainly concentrated in the western region. In the central region, the QRLs were very fragmented, falling onto all five levels. (2) The pastoral areas in Inner Mongolia differed significantly in RPL. The mean score of RPL stood at 0.3788. Nine counties/banners (50%) had an RPL greater than the mean. Contrary to the spatial layout features of QRLs, the central pastoral areas in Inner Mongolia had stronger RPLs than the eastern ones. High RPL counties/banners are mostly clustered in the central region. The spatial layout of RPLs is relatively reasonable in the central region: the RPLs decreased gradually from Dorbod Banner. (3) Nearly 45% of the pastoral areas in central and western Inner Mongolia face serious relative poverty and a high risk of returning to poverty. Eight counties/banners (45%) were identified as high composite relative poverty areas. From spatial layout, the composite relatively poor counties/banners clustered clearly, mainly in the western region. Finally, this paper establishes a warning mechanism against large-scale returning to poverty, aiming to lower composite RPL. The research results provide empirical reference and implementation path for consolidating the results of poverty eradication and facilitating rural revitalization.