Search

This study challenged the current conceptualization of social support as a static process and attempted to explore how the sources and types of social support unfolded over time during mainland Chinese immigrant women's first year of resettlement in Hong Kong. A longitudinal qualitative method was used and 15 immigrant women were recruited. In-depth interviews using a semi-structured interview guide were conducted at three-monthly intervals. Results supported our view on the 'stages within stage' assumption of the resettlement period of the migration-integration process. In the first quarter of resettlement, immigrant women mobilized a great deal of instrumental and information support from family members and kin to resolve survival issues such as finances, housing and childcare. However, the demand for instrumental support declined over time, and the need for emotional support appeared to peak at the second stage of the resettlement period. Fellow immigrant women were found to be the most significant providers of information, emotional and social companionship support to immigrant women throughout the resettlement period while the supporting roles of husbands and kin diminished. Lastly, immigrant women were less inclined to seek help from formal networks and rarely sought support from neighbors and co-workers. Socio-economic and cultural reasons were used to explain these differential support patterns during immigrants' first year of resettlement in Hong Kong, and implications for social work practices were discussed. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore whether metabolic syndrome (MetS) and its components are associated with poor outcomes in patients with acute type A aortic dissection (ATAAD) after surgery., Methods: This study included 353 patients who had undergone surgery. Demographic and clinical characteristics of the patients were collected. Subgroup, mixed-model regression, score systems, and receiver operating characteristic curve (ROC) analyses were performed., Results: Overall, 353 inpatients were assigned to the poor outcome group (n = 69) and control group (n = 284) with or without MetS. Compared to the control group, the incidence of MetS was higher in the poor outcome group. Poor outcomes were present in 0%, 4.4%, 12.3%, 47.6%, 71.4%, and 100% of the six groups who met the diagnostic criteria for MetS 0, 1, 2, 3, 4, and 5 times, respectively. For multivariable logistic regression, Body mass index (BMI) quartiles remained risk factors for poor outcomes after adjustment for other risk factors. After adjusting for potential confounding factors, the MetS was found to be an independent risk factor in several models. Assigning a score of one for each component, the AUC was 0.877 (95%CI: 0.823-0.923) in all patients, 0.864 (95%CI: 0.7945-0.935) in MetS, and 0.700 (95%CI: 0.567-0.833) in non-MetS by receiver operating characteristic., Conclusion: MetS, especially BMI, confer a greater risk of poor outcomes in ATAAD after surgery during the 3-year follow-up., Competing Interests: Declarations Ethics approval and consent to participate The study protocol was approved by the Medical Ethics Committee of the First Hospital of Hebei Medical University (Shijiazhuang, Hebei, China). Informed consent was obtained from all participants or their legal guardians. Consent for publication Yes. Methods The authors confirm that this study was conducted in accordance with the Declaration of Helsinki. All methods were performed in accordance with the relevant guidelines and regulations. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Iliac vein compression syndrome (IVCS) is a clinical condition defined as obstruction of the iliac vein caused by chronic compression imposed by various causes. Currently, the clinical role of computed tomography venography (CTV) in the diagnosis of IVCS is unclear. Accurately diagnosing IVCS using CTV may enhance the understanding of the pathological anatomy of iliac veins, which may lead to better treatment outcomes, especially for recalcitrant venous leg ulcers (VLU). We aimed to investigate diagnostic criteria, contributing clinical factors, and stenting for IVCS with VLU in this study. CTV, digital subtraction angiography (DSV), and Doppler ultrasound (DUS) data were obtained from the medical and imaging records of 62 patients. Additionally, contributing factors and stenting for IVCS were analysed. Patients (100%) had clinical, aetiological, anatomic, or pathological C6 disease. CTV reduced the procedure time and contrast medium dose and provided more information than DSV. Risk factors for IVCS with VLU included female sex (P = 0.036) and advanced age (P = 0.014). The rate of ulcer healing was lower in the IVCS group without stent implantation (P = 0.020). Significant improvements were noted in venous clinical severity scores (P < 0.001) and chronic venous insufficiency questionnaire-20 scores (P < 0.001) after stenting for IVCS with C6 ulcers. CTV provides a more accurate diagnosis than DUS and DSV and allows detection of possible causes of IVCS. Female sex and advanced age were potential contributing factors for IVCS. Satisfactory outcomes were observed with stenting in the treatment of IVCS with C6 ulcers., (© 2024. The Author(s).)

This study aimed to evaluate the long-term clinical outcomes of drug-coated drug (DCB) angioplasty for long femoropopliteal lesions in older patients with chronic limb-threatening ischemia (CLTI). In this multi-center retrospective study, we enrolled 119 patients with CLTI due to Trans-Atlantic Inter-Society Consensus (TASCII) C/D femoropopliteal lesions who underwent DCB angioplasty. A total of 119 patients with 122 limbs (TASCII C = 67, 54.9%; TASCII D = 55, 45.1%) were enrolled. At 36-month follow-up, primary patency, assisted primary patency, secondary patency, and freedom from target lesion revascularization were 47.3%, 49.8%, 59.5%, and 62.7%, respectively, and there was a significant improvement over baseline in Rutherford class (P < .001) and ankle-brachial index measurements (P < .001). Complex target lesions (P = .017) and 1 stenosis-free outflow vessel (P = .001) were risk predictors of freedom from clinically driven target lesion revascularization. Complex target lesions (P = .044), diabetes (P = .007), and 1 stenosis-free outflow vessel (P = .003) were risk predictors of restenosis. At 2 months, the ulcer healing rate was 96.3% (26/27). At 36 months, the limb salvage and survival rates were 85.8% and 83.3%, respectively. DCB angioplasty were safe and effective for older patients with CLTI attributable to femoropopliteal TASCII C/D lesions., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

We established experimental models of manganese (Mn) and iron (Fe) exposure in vitro and in vivo, and addressed the effects of manganese and iron combined exposure on the synaptic function of pheochromocytoma derived cell line 12 (PC12) cells and rat cortex, respectively. We investigated the protective effect of sodium para-aminosalicylate (PAS-Na) on manganese and iron combined neurotoxicity, providing a scientific basis for the prevention and treatment of ferromanganese combined neurotoxicity. Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to detect the expression levels of protein and mRNA related to synaptic damage. Y-maze novelty test and balance beam test were used to evaluate the motor and cognitive function of rats. Haematoxylin and eosin (H&E) and Nissl staining were performed to observe the cortical damage of rats. The results showed that the combined exposure of Mn and Fe in rats led to a synergistic effect, attenuating growth and development, and altering learning and memory as well as motor function. The combination of Mn and Fe also caused damage to the synaptic structure of PC12 cells, which is manifested as swelling of dendrites and axon terminals, and even lead to cell death. PAS-Na displayed some antagonistic effects against the Mn- and Fe-induced synaptic structural damage, growth, learning and memory impairment., (© 2024 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.)

Sodium para-aminosalicylic acid (PAS-Na) treatment for manganese (Mn) intoxication has shown efficacy in experimental and clinical studies, giving rise to additional studies on its efficacy for lead (Pb) neurotoxicity and its associated mechanisms of neuroprotection. The difference between PAS-Na and other metal complexing agents, such as edetate calcium sodium (CaNa 2 -EDTA), is firstly that PAS-Na can readily pass through the blood-brain barrier (BBB), and complex and facilitate the excretion of manganese and lead. Secondly, PAS-Na has anti-inflammatory effects. Recent studies have broadened the understanding on the mechanisms associated with efficacy of PAS-Na. The latter has been shown to modulate multifarious manganese- and lead- induced neurotoxicity, via its anti-apoptotic and anti-inflammatory effects, as well as its ability to inhibit pyroptosis, and regulate abnormal autophagic processes. These observations provide novel scientific bases and new concepts for the treatment of lead, mercury, copper, thallium, as well as other toxic encephalopathies, and implicate PAS-Na as a compound with greater prospects for clinical medical application., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The aim of study was to address the effects of manganese and iron, alone and in combination, on apoptosis of BV2 microglia cells, and to determine if combined exposure to these metals augments their individual toxicity. We used a murine microglial BV2 cell line. Cell cytotoxicity was analyzed by propidium iodide (PI) exclusion assay. Cell ROS production was analyzed by 2', 7'-dichlorofluorescin diacetate (DCFH-DA) probe staining. Pro-inflammatory cytokine production was monitored by ELISA. Cell apoptosis was analyzed by PE Annexin V/7-AAD staining. Mitochondrial membrane integrity was analyzed by flow cytometry. We used immunoblotting to analyze the effect of manganese, iron alone, or their combined exposure on the activation of caspase9, P53, Bax, and Bcl2 apoptosis signaling pathways. Caspase3 activity was determined using a Colorimetric. Manganese, iron, and their combined exposure for 24 h induced the activation of BV2 microglia cells and increased ROS production and the expression of the inflammatory cytokines, IL-1β and TNF-α. And we also found that the apoptosis rate increased, mitochondrial membrane potential decreased, apoptosis-related proteins caspase9, P53, Bax, and Bcl2 expression increased, and caspase3 activity increased. Furthermore, we found that combined manganese-iron cytotoxicity was lower than that induced by manganese exposure alone. Manganese, iron alone, or their combination exposure can induce apoptosis in glial cells. Iron can reduce the toxicity of manganese, and there is an antagonistic effect between manganese and iron., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: RigidCare is an electrolysis-based device that recently obtained approval from the US's FDA to sterilise microorganisms and remove proteins for orthokeratology (O-K) lenses. The study was conducted to investigate the device's performance in varied clinical circumstances., Methods: Trial lenses and private lenses were employed by O-K lens wearers from five hospitals for an evaluation of disinfection and sterilisation and an assessment of protein removal, respectively. Menicon multipurpose solution and protein remover were selected for use with the control group. Following the instructions, pre-cleaning lens samples, post-cleaning lens samples and residual solution samples of trial lenses of the experimental and control groups were collected for microorganism examinations by an experienced third-party testing organisation. The levels of protein deposition for these two approaches were rated by senior O-K experts. Categorical variables were analysed using statistical tests, such as the chi-squared test and Fisher's exact test., Results: The microbial positive rate detected from the pre-cleaning and post-cleaning lens samples and the residual solution of the trial lenses for the experimental and control group was 4/76 vs 1/74 (P = 0.37), 1/76 vs 0/74 (P = 1.00) and 0/76 vs 8/74 (P = 0.006), respectively. Following protein removal, the experimental group exhibited a significantly higher overall proportion of lenses rated as 'clean' or with a 'mild deposit' (96.4 %, 79/82) compared to the control group (85.7 %, 66/77), with a significant difference (P < 0.05)., Conclusion: This multi-center study demonstrated that RigidCare exhibited superior efficacy in disinfection, sterilisation and protein removal as compared to Menicon multipurpose solution and protein remover., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Neutrophils plays a crucial role in acute ischemic brain injury and have emerged as potential treatment targets to mitigate such injuries. Lysine-specific demethylase 4 A (KDM4A), a member of the histone lysine demethylase family of enzymes involved in transcriptional regulation of gene expression, is upregulated during hypoxic events. However, the exact role of KDM4A in the pathological process of ischemic stroke remains largely unexplored. Our findings reveal that there was an upregulation of KDM4A levels in reactive astrocytes within both stroke mouse models and in vitro oxygen-glucose deprivation/regeneration (OGD/R) models. Using a conditional knockout mouse, we observed that astrocytic Kdm4a knockout regulates neutrophil infiltration and alleviates brain injury following middle cerebral artery occlusion reperfusion. Furthermore, Kdm4a deficiency astrocytes displayed lower chemokine C-X-C motif ligand 1 (CXCL1) level upon OGD/R and decreased neutrophil infiltration in a transwell system. Mechanistically, KDM4A, in cooperation with nuclear factor-kappa B (NF-κB), activates Cxcl1 gene expression by demethylating histone H3 lysine 9 trimethylation at Cxcl1 gene promoters in astrocytes upon OGD/R injury. Our findings suggest that astrocyte KDM4A-mediated Cxcl1 activation contributes to neutrophil infiltration via cooperation with NF-κB, and KDM4A in astrocytes may serve as a potential therapeutic target to modulate neutrophil infiltration after stroke., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Classical Swine Fever (CSF), caused by the Classical Swine Fever Virus (CSFV), inflicts significant economic losses on the global pig industry. A key factor in the challenge of eradicating this virus is its ability to evade the host's innate immune response, leading to persistent infections. In our study, we elucidate the molecular mechanism through which CSFV exploits m6A modifications to circumvent host immune surveillance, thus facilitating its proliferation. We initially discovered that m6A modifications were elevated both in vivo and in vitro upon CSFV infection, particularly noting an increase in the expression of the methyltransferase METTL14. CSFV non-structural protein 5B was found to hijack HRD1, the E3 ubiquitin ligase for METTL14, preventing METTL14 degradation. MeRIP-seq analysis further revealed that METTL14 specifically targeted and methylated TLRs, notably TLR4. METTL14-mediated regulation of TLR4 degradation, facilitated by YTHDF2, led to the accelerated mRNA decay of TLR4. Consequently, TLR4-mediated NF-κB signaling, a crucial component of the innate immune response, is suppressed by CSFV. Collectively, these data effectively highlight the viral evasion tactics, shedding light on potential antiviral strategies targeting METTL14 to curb CSFV infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: To evaluate the relationship between amount of corneal refractive change (CRC) after wearing orthokeratology (Ortho-K) lenses and axial length (AL) growth., Methods: We retrospectively enrolled 77 patients (77 eyes) aged 8-14 years who wore Ortho-K lenses more than 12 months. We divided the patients into 2 subgroups: spherical equivalent (SE) ≤ -3.0 D and SE > -3.0 D subgroup. The sagittal and tangential curvature maps and corneal topographic data within the 8-mm diameter ring at the baseline and during follow-up visits after wearing Ortho-K lens were recorded in addition to the area, height, and volume of the CRC region. The AL data were recorded at the baseline and during follow-up visits. Multivariate linear regression was conducted to analyze associations between the area, height, and volume of the CRC region, AL elongation, and SE., Results: The average change in the CRC region was 9.77 ± 0.60 D in height, 16.66 ± 3.61 mm 2 in area, and 87.47 ± 8.96 D*mm 2 in volume on the tangential diagram after wearing Ortho-K lenses for 3 months. The AL showed a change of 0.19 ± 0.14 mm after 1 year of Ortho-K lens wear (P < 0.05). At 1 year, AL elongation was negatively correlated with the area (P = 0.019) and volume (P < 0.001) of the CRC region. At 1 year, for every 1-mm 2 increase in the area and every 1-D*mm 2 increase in the volume of the CRC region, the average AL elongation decreased by 0.01 mm and 0.002 mm, respectively, in the multivariate analysis. In patients with SE ≤ -3.0 D, AL elongation was negatively correlated with the CRC-region volume (β = -0.002, P = 0.018), and in patients with SE > -3.0 D, AL elongation was negatively correlated with the CRC-region area (β = -0.017, P = 0.016)., Conclusions: The AL elongation-control efficacy of Ortho-K lenses may be related to the area and volume of the CRC region., (© 2023. The Author(s).)

Purpose: To explore the correlation between the axial length (AL) difference (myopic and nonmyopic eye) and the refractive error in children with unilateral myopia anisometropia (UMA) and to elucidate its clinical application in the process of Ortho-K lenses review following nonstop wearing., Methods: This study retrospectively analyzed the data of 70 children with UMA (age, 8-15 years) whose myopic eyes were treated with Ortho-K lenses. The spherical equivalent refractive errors (SERE) of the myopic eye ranged from -0.75 D to -4.25 D, and astigmatism was no less than -1.50 D. In addition, SERE of nonmyopic eyes were no less than -0.50 D. AL, and the refractive data of both eyes were measured at baseline. A multivariate linear regression was used to analyze the relationship between the AL difference and refractive error, and paired t -test was used to analyze the changes in AL in both eyes., Results: Every 1 mm axial length change corresponds to -1.627 D (95% CI: -1.921 D, -1.333 D; P < 0.001) change in refractive error in children. The association between the AL change and the degree of myopia did not change with age ( P =0.751). Among the 70 subjects, 51 (72.86%) had myopia in the right eye, and the 95% confidence interval (CI) for myopia occurring in the right eye was 62.4%-83.3%. The paired t -test showed that the average AL growth was significantly slower in myopic eyes treated with Ortho-K lenses than in nonmyopic eyes ( t  = 9.805, P < 0.001)., Conclusion: Every 1 mm AL change would cause an average refractive error increase. Age did not influence the association between AL changes and the degree of myopia. The right eye is more likely to be affected in children with UMA. The Ortho-K lens treatment slowed down the growth of AL in the myopic eye in children with UMA., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2023 Lu Sun et al.)

Objective: To study the effects of early sequential enteral nutrition (ESEN) therapy and early non-sequential enteral nutrition (EN) therapy on the nutritional status, recovery, and quality of life of patients who undergo postoperative chemotherapy for esophageal cancer., Patients and Methods: The data of 90 patients who underwent postoperative chemotherapy for esophageal cancer in Gansu Provincial Cancer Hospital from January 2018 to June 2020 were analyzed retrospectively. Patients were divided the Test group and the Control group (n=45 each) based on the method of nutritional support. Patients in the Control group were treated with non-sequential early enteral nutrition and the Test group treated with sequential early enteral nutrition until the discharge. Nutritional status, recovery, and quality of life of the chemotherapy patients in the two groups were compared., Results: After the intervention, the pre-protein, albumin and hemoglobin levels were higher in the Test group than in the control group (p<0.05). Postoperative exhaustion, incision healing and length of hospital stay were significantly lower in the Test group than in the Control group (p<0.05), while the scores on all dimensions of the short-form 36 health survey scale (SF-36) and the total score were higher than in the Control group (p<0.05)., Conclusions: Sequential early enteral nutrition may be used for patients who undergo chemotherapy after esophageal cancer surgery to promote their early recovery and improve their quality of life and nutritional status.

Objective: To analyze the proper time and method for treatment of prostatic abscess (PA)., Methods: This is a retrospective study that included 18 patients diagnosed with and treated for prostatic abscess between February 2017 and July 2022. After obtaining data from the patients' medical records, we analyzed their clinical features as well as the therapeutic methods opted for and their effectiveness. Results： Of the 18 patients included, one achieved a full recovery after a spontaneous rupture of the abscess. Transrectal ultrasound (TRUS)-guided aspiration was performed in the remaining 17 patients, of whom 14 had a complete resolution after this procedure whereas 3 experienced recurrence. The recurrent cases were successfully managed with transurethral (TU) de-roofing., Conclusion: TRUS-guided aspiration is a treatment modality with a marked curative effect for simple PAs. For refractory abscesses (recurrent, multifocal, incomplete or unsuccessful drainage) or PA located near the urethra, TU de-roofing can be considered as a first choice to shorten the course of the disease and alleviate the medical treatment expenses due to recurrence.

Background: Home oxygen therapy (HOT) is indicated upon discharge in some preterm infants with severe bronchopulmonary dysplasia (BPD). There is a lack of evidence-based consensus on the indication for HOT among these infants. Because wide variation in the institutional use of HOT exists, little is known about the role of regional social-economic level in the wide variation of HOT., Methods: This was a secondary analysis of Chinese Neonatal Network (CHNN) data from January 1, 2019 to December 31, 2019. Infants at gestational ages < 32 weeks, with a birth weight < 1500 g, and with moderate or severe BPD who survived to discharge from tertiary hospitals located in 25 provinces were included in this study. Infants with major congenital anomalies and those who were discharged against medical advice were excluded., Results: Of 1768 preterm infants with BPD, 474 infants (26.8%) were discharged to home with oxygen. The proportion of HOT use in participating member hospitals varied from 0 to 89%, with five of 52 hospitals' observing proportions of HOT use that were significantly greater than expected, with 14 hospitals with observing proportions significantly less than expected, and with 33 hospitals with appropriate proportions. We noted a negative correlation between different performance groups of HOT and median GDP per capita (P = 0.04)., Conclusions: The use of HOT varied across China and was negatively correlated with the levels of provincial economic levels. A local HOT guideline is needed to address the wide variation in HOT use with respect to different regional economic levels in countries like China., (© 2022. The Author(s).)

Background: As one of the most common causes of stroke, symptomatic intracranial artery stenosis (sICAS) is a great threat to public health, and its financial burden is substantial, with annual direct high medical costs particularly in China. Currently, the long-term use of conventional dual antiplatelet therapy (DAPT) as the primary modality of treatment for sICAS decreases the risk of stroke recurrence but increases the risk of bleeding. We aimed to evaluate the efficacy and safety of low dose aspirin plus clopidogrel for the treatment of sICAS in the elderly population., Methods: This randomized, controlled study included 181 older patients with transient ischemic attack (TIA) or ischemic stroke (IS) attributed to sICAS, who were recruited between April 2015 and November 2020. The 90 patients assigned to the low dose therapy group included aspirin, 75 mg, plus clopidogrel, 50 mg, daily for 90 and 91 patients assigned to the conventional group included aspirin, 100 mg, plus clopidogrel, 75 mg, daily for 90 days (aspirin or clopidogrel alone daily thereafter) were included in this intention-to-treat analysis. Efficacy and safety analyses were done in this trial., Results: One hundred eighty-one eligible elderly patients with sICAS were enrolled in this trial. The median age was 70 years ranged 60-83 years. Seventy-five participants were with TIA and 106 with IS. The median time of follow-up was 30 months ranged 1-36 months. Ninety patients were assigned randomly to the low dose group and 91 patients to the conventional group. The rate of primary, secondary and composite efficacy were not significantly different between the low dose and conventional group ( P > 0.05). The rate of composite safety outcome was 7.8% (7/90) in the low dose group, which was lower than 17.6% (16/91) in the conventional group (χ 2 = 3.921, P = 0.048). At the time of last follow-up, 17 (9.4%) of 181 patients developed GI injuries, which occurred in four (4.4%) of 90 patients in the low dose group and in 13 (14.3%) of 91 patients in the conventional group (χ 2 = 4.058, P = 0.044). The primary efficacy outcome occurred in six (18.2%) of 33 patients with severe sICAS and in 22 (38.6%) of 57 patients with moderate sICAS (χ 2 = 4.064, P = 0.044) in the low dose group., Conclusion: In this study, the safety of low dose aspirin combined with clopidogrel proved to be equally efficient and significantly safer than those of conventional dose within 24 months in elderly patients with sICAS. However, the small size of this study limits the validity of the results. Further larger longitudinal and randomized controlled trials are necessary to evaluate the role of low dose DAPT in the patients with sICAS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Song, Zhang, Liu, Shi, Wang, Lu, Yao and Chen.)

Background: Combined exposure to lead and cadmium is common in occupational environments. However, the effects of co-exposure to Pb-Cd on neurotoxicity have not been fully clarified. Sodium para-aminosalicylic acid (PAS-Na) has previously been shown to protect neurons from Pb-induced toxicity. This study aimed to investigate the beneficial effect of PAS-Na against co-exposure to Pb-Cd-induced neurodegeneration in SH-SY5Y cells., Methods: The MTT assay was used to detect the effects of Pb and Cd alone, or in combination, on SH-SY5Y cell survival. The effects of Pb and Cd alone or in combination on oxidative stress were assessed by reactive oxygen species (ROS) level. Nrf2, the master switch for antioxidant responses, was detected by immunofluorescence. Protein expression levels of PI3K, Akt, p-Akt, Nrf2 and HO-1 were determined by Western blot analysis., Results: MTT assay results established that the survival rate of SH-SY5Y cells was not significantly affected by exposure to 1 μmol/L lead, 0.25 μmol/L cadmium, and 1-fold Pb-Cd mixture (1 μmol/L Pb + 0.25 μmol/L Cd), while 10-fold Pb-Cd combined exposure (10 μmol/L Pb + 2.5 μmol/L Cd) significantly reduced the survival rate of SH-SY5Y cells. Combined Pb-Cd exposure significantly increased intracellular ROS levels, and N-Acetyl-L-cysteine (NAC) treatment in the 10 μmol/L Pb + 2.5 μmol/L Cd group significantly decreased ROS expression levels, attenuating the levels of oxidative stress. Protein expression of PI3K and p-Akt significantly decreased in the 10 μmol/L Pb + 2.5 μmol/L Cd group, while the expression of PI3K and p-Akt protein increased after PAS-Na intervention. Immunofluorescence analysis showed that levels of Nrf2 in the nucleus increased in the 10 μmol/L Pb + 2.5 μmol/L Cd group, along with Nrf2 protein levels, suggesting that Nrf2 was translocated from the cytoplasm into the nucleus upon combined Pb-Cd exposure. In addition, HO-1 protein expression level, a downstream gene product of Nrf2, was increased. In response to NAC intervention, HO-1 protein expression levels significantly decreased. PAS-Na had the same intervention effect as NAC., Conclusion: Combined exposure to Pb-Cd induced oxidative stress and cytotoxicity in SH-SY5Y cells. PAS-Na displayed antagonistic effects on neurodegenerative changes induced by combined Pb-Cd exposure; hence, it may afford a novel treatment modality for exposure to these metals.

Lead (Pb) is a developmental neurotoxin that can disrupt brain development and damage the brain regions responsible for executive function, behavioral regulation and fine motor control. Sodium para-aminosalicylic acid (PAS-Na) is a non-steroidal anti-inflammatory drug that can cross the blood-brain barrier. The purpose of this study was to examine the effects of juvenile rat Pb exposure on behavioral changes and brain inflammation, and the efficacy of PAS-Na in ameliorating these effects. The results showed that Pb exposure during the juvenile period (from weaning to adult period) delayed rats' growth development and impaired their motor learning. Pb exposure not only increased Pb concentrations in several brain regions (including hippocampus, striatum and substantia nigra), but also disrupted metal-homeostasis in the brain, as higher levels of iron (Fe) and calcium (Ca) were observed in the substantia nigra. Moreover, Pb activated the MAPK pathway and increased levels of inflammatory factors such as IL-1β, TNF-α and IL-6 in the hippocampus, striatum and substantia nigra. Furthermore, Pb increased the levels of alpha-synuclein (α-syn) in these brain sites. PAS-Na improved the motor deficits and brain inflammation in the Pb-exposed rats. Moreover, the elevated Pb, Fe and Ca concentrations in the brain were significantly reduced by PAS-Na, which contains amino, carboxyl and hydroxyl functional groups, suggesting that it may act as a chelator of brain metals. In addition, PAS-Na inhibited the Pb-induced MAPK pathway activation and α-syn accumulation in the same brain regions. Taken together, our novel study suggest that PAS-Na shows efficacy in improving the Pb-induced behavioral changes in rats by inhibiting MAPK-dependent inflammatory pathways and reducing α-syn accumulation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The invasive insect pest, Frankliniella occidentalis, is a well-known vector that transmits a variety of ornamental and vegetable viruses. The mechanistic basis of sex determination in F. occidentalis is not well understood, and this hinders our ability to deploy sterile insect technology as an integrated pest management strategy. In this study, six cDNA libraries from female and male adults of F. occidentalis (three biological replicates each) were constructed and transcriptomes were sequenced. A total of 6000 differentially-expressed genes were identified in the two sexes including 2355 up- and 3645 down-regulated genes. A total of 149 sex-related genes were identified based on GO enrichment data and included transformer-2 (tra2), fruitless (fru), male-specific lethal (msl) and sex lethal (sxl); several of these exhibited sex-specific and/or sex-biased expression in F. occidentalis. This study contributes to our understanding of the sex-determined cascade in F. occidentalis and other members of the Thysanoptera., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The antiknock additive methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese(Mn) compound. Mn neurotoxicity caused by occupational Mn exposure (mostly inorganic MnCl 2 ) is associated with motor and cognitive disturbances, referred to as Manganism. However, the impact of environmentally relevant Mn exposure on MMT-induced Manganism is poorly understood. In this investigation, we studied the effects of MMT on motor function and brain structure, and compared its effects with those of inorganic MnCl 2 . After adaptive feeding for 7 days, male and female Sprague-Dawley (SD) rats in the MMT-treated groups and positive control group were treated for 8 weeks with MMT (1, 2 and 4 mg/kg/i.g.) or MnCl 2 ·4H 2 O (200 mg/kg/i.g.). Mn content in blood, liver, spleen and distinct brain regions was determined by inductively coupled plasma-mass spectrometer (ICP-MS). We found that MMT and MnCl 2 exposure led to slower body-weight-gain in female rats, impaired motor and balance function and spatial learning and memory both in male and female rats. HE staining showed that MMT and MnCl 2 led to altered structure of the substantia nigra pars compacta (SNpc), and Nissl staining corroborated MMT's propensity to damage the SNpc both in male and female rat. In addition, Immunostaining of the SNpc showed decreased TH-positive neurons in MMT- and MnCl 2 -treated rats, concomitant with Iba1 activation in microglia. Moreover, no statistically significant difference was noted between the rats in the H-MMT and MnCl 2 groups. In summary, these findings suggest that MMT and MnCl 2 exposure cause ultrastructural changes in the SNpc neurons culminating in altered motor behavior and cognition, suggesting that altered SNpc structure and function may underline the motor and cognitive deficits inherent to Manganism, and accounting for MMT and MnCl 2 's manifestations of atypical parkinsonism., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Small heat shock proteins (sHSPs) help prevent the irreversible aggregation of denatured proteins that occurs in response to organismal stress. In this study, we identified two intron-free genes encoding sHSPs from Frankliniella occidentalis; these were designated FoHSP11.6 and FoHSP28.0 and belonged to an atypical and typical sHSP family, respectively. Both FoHSPs were transcribed in all developmental stages of F. occidentalis with the highest expression levels in pupae and adults and greater expression in males than females. Although the FoHSPs had different temperature-induced expression profiles, they were generally induced by both low and high temperatures and reached maximal expression levels after 0.5-1 h of temperature stress. The FoHSPs expression levels in pupae were induced by drought and high humidity, and higher expression levels were correlated with lower survival rates. The thermotolerance of F. occidentalis decreased when theFoHSPs were silenced by RNA interference. Our results show that FoHSP11.6 and FoHSP28.0 are involved in the response to temperature and drought and may also function in growth and development of F. occidentalis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a multisystem autoimmune disease with small-vessel involvement. In AAV, microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are major clinicopathologic variants. In addition, myeloperoxidase (MPO) and proteinase 3 (PR3) are major target antigens. The objective of the study was to explore the predictive factors for long-term survival in AAV patients., Materials and Methods: A multicenter retrospective study was carried out on 407 patients between 2005 and 2020. Clinical parameters were obtained from laboratory tests including the ANCA types, antinuclear antibody (ANA), extractable nuclear antigen (ENA), anti-streptolysin O (ASO), glomerular filtration rate (GFR), and the laboratory examinations for the blood routine, liver function, renal function, and immunity, etc. The data for clinical parameters were collected from electronic medical records (EMRs), and the data for patient survival were acquired through regular follow-up. The association of clinical parameters with overall survival (OS) along with 3-year and 5-year survival rates was analyzed, and the nomogram as a predictive model was established according to the analysis results., Results: In the present study, 336 (82.6%) patients and 46 (11.3%) patients were diagnosed with MPA and GPA, respectively. The mean and median OS for all the patients were 2,285 and 2,290 days, respectively. The 1-year, 3-year, 5-year, and 10-year cumulative survival rates for all the patients were 84.2%, 76.3%, 57.2%, and 32.4%, respectively. Univariate and multivariate survival analyses indicated that the independent prognostic factors included age, pathological categories (MPA, GPA, and other types), serum ANCA types (negative or positive for MPO and/or PR3), ANA, ASO, GFR, lymphocyte, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP), and these clinical parameters except for ASO were used to construct a nomogram. The nomogram for 3-year and 5-year survival rates had a C-index of 0.721 (95% CI 0.676-0.766). The calibration curves showed that the predicted values of the nomogram for 3-year and 5-year survival rates were generally consistent with practical observed values, and decision curve analysis (DCA) further demonstrated the practicability and accuracy of the predictive model., Conclusion: Laboratory tests at diagnosis have great significance in the prediction of long-term survival in AAV patients., Competing Interests: Author K-WZ was employed by Guangzhou Baiyunshan Pharmaceutical Holding Co., Ltd., Baiyunshan Pharmaceutical General Factory, Guangzhou, China. Author WZ was employed by Yangquan Coal Industry (Group) General Hospital, Yangquan, China. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liao, Ren, Zhu, Qin, Mo, Cong, Wu, Wang, Cui, Xu, Guo, Zhang, Song, Zhang, Yang, Tang, Li, Xie, Li, Wang, Zhou, Wei, Chen and Shi.)

Wine colour is an essential organoleptic property considered by consumers. In this paper, the potential effects on colour characteristics and the content of main phenolic compounds in red wine under microwave irradiation were investigated during wine storage. The results showed that the changing trend of colour characteristics of microwave-treated and untreated wines was very similar. Moreover, total phenolic compounds, total monomeric anthocyanins, main anthocyanins, main flavonoids, and main phenolic acids (gallic acid; caffeic acid; syringic acid; (+)-catechin; Cy-3-glu; Mv-3-glu) also showed similar change trends during storage. In other words, microwave irradiation had a long-term effect on the colour properties and main phenolic compounds of red wine, changes that require long-time aging in traditional processing. In terms of the studied parameters, the changes in microwave-treated wine were faster than those in untreated wine. These results showed that microwave technology, as a promising artificial aging technology, could in a short time produce red wine of similar quality to traditional aging.

Hypertonic dextrose prolotherapy (HDP) is an injection of a concentrated dextrose solution for the purpose of local treatment of musculoskeletal pain and possible enhancement of repair mechanisms. This systematic review and meta-analysis examines the clinical utility of HDP injection for treatment of knee osteoarthritis (OA). Randomized controlled trials (RCTs) utilizing HDP to treat knee OA were retrieved from MEDLINE, EMBASE, and Cochrane Library (CENTRAL). Identification and inclusion of RCTs utilizing intra-articular and extra-articular administration of HDP vs administration of other injectate or physical therapy as control for knee OA were included. Primary clinical outcomes were changes in knee WOMAC, pain and function score. Secondary outcomes were adverse events related to HDP. For continuous outcomes with same or different measurements, we calculated, respectively the weighted mean difference (WMD) or the standardized mean difference (SMD), respectively. Results were pooled using DerSimonian and Laird random effect models across the included studies and heterogeneity between studies was estimated using the I 2 index. Five studies comprising a total of 319 treated patients met inclusion criteria and were included in the final analysis. At a mean of 22.8 weeks follow-up, HDP treatment significantly improved total WOMAC score (WMD = 13.77, 95% CI: 6.75-20.78; p < 0.001; I 2  = 90%), pain (SMD = 1.33, 95% CI: 0.49-2.17; p < 0.001; I 2  = 91%) and knee function (SMD = 1.30, 95% CI: 0.45-2.14; p < 0.001; I 2  = 91%) compared with control group. There were no severe adverse events related to dextrose injection reported in all the included studies. HDP is a promising treatment for knee OA with a reasonable safety profile. Further research in mechanism of HDP activity and long-term follow-up study will be needed for exploring this novel therapy modality., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: This study aimed to compare the changes in the axial length (AL) in myopic children that wear centered and decentered orthokeratology (Ortho-K)., Methods: This retrospective study included 217 subjects who were treated with an Ortho-K lens for >12 months. The subjects were divided into three groups based on the magnitude of the Ortho-K lens treatment zone decentration: mildly, moderately, and severely decentered groups. Distance and direction of treatment zone decentration were calculated using software that was developed in-house. The AL changes in different groups were compared., Results: Based on the distance of the treatment zone decentration, 65 children (65 eyes) were included in the mildly decentered group, 114 children (114 eyes) in the moderately decentered group, and 38 children (38 eyes) in the severely decentered group. The mean decentration distance in the three groups was 0.35 ± 0.11 mm, 0.71 ± 0.13 mm, and 1.21 ± 0.22 mm, respectively. The mean AL increase in the three groups after 12 months of Ortho-K lens wear was 0.24 ± 0.21 mm, 0.23 ± 0.18 mm, and 0.19 ± 0.20 mm, respectively. There were no significant differences in AL changes among the three groups., Conclusions: Ortho-K lens decentration is common in clinical practice. The AL change after Ortho-K lens wear was not significantly different in subjects with different magnitudes of Ortho-K lens decentration. Fitting the Ortho-K lens in the properly centered zone is recommended to ensure the safety of Ortho-K lens wear and to maintain visual quality., (© 2022. The Author(s).)

TP53 is the most frequently mutated gene in cancer, yet these mutations remain therapeutically non-actionable. Major challenges in drugging p53 mutations include heterogeneous mechanisms of inactivation and the absence of broadly applicable allosteric sites. Here we report the identification of small molecules, including arsenic trioxide (ATO), an established agent in treating acute promyelocytic leukemia, as cysteine-reactive compounds that rescue structural p53 mutations. Crystal structures of arsenic-bound p53 mutants reveal a cryptic allosteric site involving three arsenic-coordinating cysteines within the DNA-binding domain, distal to the zinc-binding site. Arsenic binding stabilizes the DNA-binding loop-sheet-helix motif alongside the overall β-sandwich fold, endowing p53 mutants with thermostability and transcriptional activity. In cellular and mouse xenograft models, ATO reactivates mutant p53 for tumor suppression. Investigation of the 25 most frequent p53 mutations informs patient stratification for clinical exploration. Our results provide a mechanistic basis for repurposing ATO to target p53 mutations for widely applicable yet personalized cancer therapies., Competing Interests: Declaration of Interests M.L., J.-L.W., and H.-X.S. are co-authors of the pending patents “PANDA as a novel therapeutic” (PCT/CN2018/085190) and “mp53 rescue compounds and methods of treating a p53 disorder” (PCT/CN2019/070117). The authors declare no other competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A convenient method for deoxyfluorination of aromatic and aliphatic carboxylic acids with CF 3 SO 2 OCF 3 in the presence of a suitable base at room temperature has been developed. The reaction allows a straightforward access to a variety of acyl fluorides and proves that CF 3 SO 2 OCF 3 is an effective deoxyfluorination reagent for carboxylic acids. The method features simplicity, expeditiousness, high efficiency, ease of handling, good functional group tolerance, a wide range of substrates, excellent yields of products, compatibility of many amine initiators, use of environmentally friendly reagents, and effortless removal of byproducts. This reaction represents the first utilization of trifluoromethyl trifluoromethanesulfonate as a fluorination reagent., (© 2020 Wiley-VCH GmbH.)

Background: Heart failure (HF) is the terminal stage of all cardiovascular events. Although implantable cardioverter defibrillator (ICD) therapies have reduced mortality among the high-risk HF population, it is necessary to determine whether certain factors can predict mortality even after cardiac device implantation. Growth stimulation expressed gene 2 (ST2) is an emerging biomarker for HF patient stratification in different clinical settings., Aims: This study aimed to investigate the relationship between baseline soluble ST2 (sST2) levels in serum and the clinical outcomes of high-risk HF patients with device implantation., Methods: Between January 2017 and August 2018, we prospectively recruited consecutive patients implanted with an ICD for heart failure, with LVEF ≤35% as recommended, and analyzed the basic characteristics, baseline serum sST2, and NT-proBNP levels, with at least 1-year follow-up. All-cause mortality was the primary endpoint., Results: During a 643-day follow-up, all-cause mortality occurred in 16 of 150 patients (10.67%). Incidence of all-cause mortality increased significantly in patients with sST2 levels above 34.98846 ng/ml (16.00% vs . 5.33%, P = 0.034). After adjusting the model (age, gender, device implantation, prevention of sudden death, LVEDD, LVEF, WBC and CLBBB, hsTNT, etiology, and eGFR) and the model combined with NT-proBNP, the risk of all-cause death was increased by 2.5% and 1.9%, respectively, per ng/ml of sST2. The best sST2 cutoff for predicting all-cause death was 43.42671 ng/ml (area under the curve: 0.72, sensitive: 0.69, and specificity: 0.69). Compared to patients with sST2 levels below 43.42671 ng/ml, the risk of all-cause mortality was higher in those with values above the threshold (5.1% vs. 21.2%, P = 0.002). ST2 level ≥43.42671 ng/ml was an independent predictor of all-cause mortality (HR: 3.30 [95% CI 1.02-10.67]). Age (HR: 1.06 [95% CI: 1.01-1.12]) and increased NT-proBNP per 100 (HR: 1.02 [95% CI: 1.01-1.03]) were also associated with all-cause mortality in ICD patients., Conclusions: sST2 level was associated with risk of all-cause mortality, and a threshold of 43.43 ng/ml showed good distinguishing performance to predict all-cause mortality in patients with severe heart failure, recommended for ICD implantation. Patients with sST2 levels more than 43.42671 ng/ml even after ICD implantation should therefore be monitored carefully., Competing Interests: All authors report no relationships that could be construed as conflicts of interest., (Copyright © 2020 Zhi-wei Hou et al.)

Vagus nerve stimulation (VNS) restores autonomic balance, suppresses inflammation action and minimizes cardiomyocyte injury. However, little knowledge is known about the VNS' role in cardiomyocyte phenotype, sarcomere organization, and energy metabolism of infarcted hearts. VNS in vivo and acetylcholine (ACh) in vitro optimized the levels of α/β-MHC and α-Actinin positive sarcomere organization in cardiomyocytes while reducing F-actin assembly of cardiomyocytes. Consistently, ACh improved glucose uptake while decreasing lipid deposition in myocytes, correlating both with the increase of Glut4 and CPT1α and the decrease of PDK4 in infarcted hearts in vivo and myocytes in vitro, attributing to improvement in both glycolysis by VEGF-A and lipid uptake by VEGF-B in response to Ach. This led to increased ATP levels accompanied by the repaired mitochondrial function and the decreased oxygen consumption. Functionally, VNS improved the left ventricular performance. In contrast, ACh-m/nAChR inhibitor or knockdown of VEGF-A/B by shRNA powerfully abrogated these effects mediated by VNS. On mechanism, ACh decreased the levels of nuclear translocation of FoxO3A in myocytes due to phosphorylation of FoxO3A by activating AKT. FoxO3A overexpression or knockdown could reverse the specific effects of ACh on the expression of VEGF-A/B, α/β-MHC, Glut4, and CPT1α, sarcomere organization, glucose uptake and ATP production. Taken together, VNS optimized cardiomyocytes sarcomere organization and energy metabolism to improve heart function of the infarcted heart during the process of delaying and/or blocking the switch from compensated hypertrophy to decompensated heart failure, which were associated with activation of both P13K/AKT-FoxO3A-VEGF-A/B signaling cascade.

Improving crop nitrogen (N) limitation adaptation (NLA) is a core approach to enhance N use efficiency (NUE) and reduce N fertilizer application. Rapeseed has a high demand for N nutrients for optimal plant growth and seed production, but it exhibits low NUE. Epigenetic modification, such as DNA methylation and modification from small RNAs, is key to plant adaptive responses to various stresses. However, epigenetic regulatory mechanisms underlying NLA and NUE remain elusive in allotetraploid B. napus . In this study, we identified overaccumulated carbohydrate, and improved primary and lateral roots in rapeseed plants under N limitation, which resulted in decreased plant nitrate concentrations, enhanced root-to-shoot N translocation, and increased NUE. Transcriptomics and RT-qPCR assays revealed that N limitation induced the expression of NRT1.1 , NRT1.5 , NRT1.7 , NRT2.1/NAR2.1 , and Gln1;1 , and repressed the transcriptional levels of CLCa , NRT1.8 , and NIA1 . High-resolution whole genome bisulfite sequencing characterized 5094 differentially methylated genes involving ubiquitin-mediated proteolysis, N recycling, and phytohormone metabolism under N limitation. Hypermethylation/hypomethylation in promoter regions or gene bodies of some key N-metabolism genes might be involved in their transcriptional regulation by N limitation. Genome-wide miRNA sequencing identified 224 N limitation-responsive differentially expressed miRNAs regulating leaf development, amino acid metabolism, and plant hormone signal transduction. Furthermore, degradome sequencing and RT-qPCR assays revealed the miR827-NLA pathway regulating limited N-induced leaf senescence as well as the miR171- SCL6 and miR160- ARF17 pathways regulating root growth under N deficiency. Our study provides a comprehensive insight into the epigenetic regulatory mechanisms underlying rapeseed NLA, and it will be helpful for genetic engineering of NUE in crop species through epigenetic modification of some N metabolism-associated genes.

Progress in the transition-metal-catalyzed or -free fluoroalkylation of diazo compounds with different types of fluoroalkyl (R fn ) transfer reagents is summarized in this review. Special attention is focused on the straightforward trifluoromethylation, gem-difluoroolefination, trifluoromethoxylation, fluoroalkylthiolation, and trifluoromethylselenolation of diazo substrates. The mechanistic insights and the application of some of the products are also discussed in this article. We believe that this review will inspire both young and experienced chemists to further study the direct fluoroalkylation of diazo compounds as an efficient and convenient way to build complex fluorine-containing molecules., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Nitrogen (N) is essential for plant growth and crop productivity. Organic N is a major form of remobilized N in plants' response to N limitation. It is necessary to understand the regulatory role of N limitation adaption (NLA) in organic N remobilization for this adaptive response. Transcriptional and proteomic analyses were integrated to investigate differential responses of wild-type (WT) and nla mutant plants to N limitation and to identify the core organic N transporters targeted by NLA. Under N limitation, the nla mutant presented an early senescence with faster chlorophyll loss and less anthocyanin accumulation than the WT, and more N was transported out of the aging leaves in the form of amino acids. High-throughput transcriptomic and proteomic analyses revealed that N limitation repressed genes involved in photosynthesis and protein synthesis, and promoted proteolysis; these changes were higher in the nla mutant than in the WT. Both transcriptional and proteomic profiling demonstrated that LHT1, responsible for amino acid remobilization, were only significantly upregulated in the nla mutant under N limitation. These findings indicate that NLA might target LHT1 and regulate organic N remobilization, thereby improving our understanding of the regulatory role of NLA on N remobilization under N limitation.

Background: Human cellular repressor of E1A-stimulated genes (CREG) is a secreted glycoprotein that attenuates angiotensin II-induced hypertension, alleviates myocardial fibrosis, and improves heart function. However, the role of CREG in high-salt (HS) diet-induced hypertensive nephropathy is unclear., Methods: To determine the effects and molecular mechanisms of CREG in HS diet-induced hypertensive nephropathy, we established a hypertensive nephropathy animal model in Dahl salt-sensitive (SS) rats fed a HS diet (8% NaCl, n = 20) for 8 weeks. At week 4 of HS loading, these rats were administered recombinant CREG (reCREG; 35 µg/kg·day, n = 5) and saline (n = 5) via subcutaneously implanted pumps and were also administered the vasodilator hydralazine (20 mg/kg·day, n = 5) in drinking water. We used hematoxylin and eosin staining, Masson's trichrome staining, immunohistochemical labeling, western blotting, RT-PCR, and Tunel staining to determine the signaling pathways of CREG in HS diet-induced hypertensive nephropathy., Results: After 8 weeks of HS intake, the Dahl SS rats developed renal dysfunction and severe renal fibrosis associated with reductions of 78 and 67% in CREG expression, respectively, at both mRNA and protein levels in the kidney. Administration of reCREG improved renal function and relieved renal fibrosis. Administration of CREG also inhibited monocyte infiltration and reduced apoptosis in the kidney cells. CREG overexpression upregulated forkhead box P1 expression and inhibited the transforming growth factor-β1 signaling pathway., Conclusion: Our study shows that CREG protected the kidney against HS-diet-induced renal damage and provides new insights into the mechanisms underlying kidney injury., (© 2020 S. Karger AG, Basel.)

Hemiplegic shoulder pain (HSP), which occurs in most patients with hemiplegia, causes considerable distress and worsens outcomes in rehabilitation. Although they have received the treatments such as anti-inflammatory drugs or physical therapy, many of the individuals remain suffering from shoulder pain 6 months after acute stroke event. In this retrospective study, we evaluated the effectiveness of ultrasound guided subacromial-subdeltoid (SASD) bursa injections with botulinum toxin type A (BoNT/A) compared to steroids for refractory HSP.The data were collected retrospectively by reviewing the patient's medical records and pain questionnaires in our rehabilitation center. In total, 38 patients who received ultrasound guided SASD bursa injection (BoNT/A group, n = 18; corticosteroid group, n = 20) were included. The pain visual analog scale (VAS) score at rest and during arm passive abduction, Fugl-Meyer score of upper limbs (F-M score) were evaluated before, 2, 4, 8, and 12 weeks after injection.Both 2 groups obtained a significant improvement of VAS score at rest or during arms passive abduction compared to baseline score (within group compare, P < .05). There were no significant differences of pain score improvement between two groups at week 2, 4, 8, and 12 after injection either at rest or during passive arm abduction (between 2 groups compare, P > .05). There were also no differences in results of the post treatment F-M score between 2 groups (between 2 groups compare, P > .05). Similarly, during the follow-up period no collateral effects were reported after BoNT/A injection.SASD bursa BoNT/A injection can substantially reduce the pain as corticosteroid in patients with HSP. BoNT/A injection could be a useful strategy for replacing steroids as a treatment for refractory HSP especially in the patients who cannot tolerate the steroids injection.

Background: The benefits of volatile anesthetics in coronary artery bypass grafting (CABG) patients remain controversial. We aimed to conduct an updated meta-analysis to assess whether the use of volatile anesthetics during CABG could reduce mortality and other outcomes., Methods: We searched eight databases from inception to June 2019 and included randomized controlled trials (RCTs) comparing the effects of volatile anesthetics versus total intravenous anesthesia (TIVA) in CABG patients. The primary outcomes were operative mortality and one-year mortality. The secondary outcomes included the length of stay in the intensive care unit (ICU) and hospital and postoperative safety outcomes (myocardial infarction, heart failure, arrhythmia, stroke, delirium, postoperative cognitive impairment, acute kidney injury, and the use of intra-aortic balloon pump (IABP) or other mechanical circulatory support). Trial sequential analysis (TSA) was performed to control for random errors., Results: A total of 89 RCTs comprising 14,387 patients were included. There were no significant differences between the volatile anesthetics and TIVA groups in operative mortality (relative risk (RR) = 0.92, 95% confidence interval (CI): 0.68-1.24, p = 0.59, I2 = 0%), one-year mortality (RR = 0.64, 95% CI: 0.32-1.26, p = 0.19, I2 = 51%), or any of the postoperative safety outcomes. The lengths of stay in the ICU and hospital were shorter in the volatile anesthetics group than in the TIVA group. TSA revealed that the results for operative mortality, one-year mortality, length of stay in the ICU, heart failure, stroke, and the use of IABP were inconclusive., Conclusions: Conventional meta-analysis suggests that the use of volatile anesthetics during CABG is not associated with reduced risk of mortality or other postoperative safety outcomes when compared with TIVA. TSA shows that the current evidence is insufficient and inconclusive. Thus, future large RCTs are required to clarify this issue., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Physiologically-based pharmacokinetic (PBPK) modeling offers a unique modality to predict age-specific pharmacokinetics. The objective of this study was to assess the ability of PBPK model to predict plasma exposure of oxycodone, a widely used opioid for pain management, in adults and children., Methods: A full PBPK model of oxycodone following intravenous and oral administration was developed using a 'bottom-up' and 'top-down' combined strategy. The model was then extrapolated to pediatrics through a reasonable scaling method. The adult and pediatric model was evaluated using data from 17 clinical PK studies by testing predicted/observed goodness of fit. The mean fold error for PK parameters was calculated. Finally, we used the validated PBPK model to visualize adult-children dose conversion for oxycodone., Results: The developed PBPK model successfully predicted the oxycodone disposition in adults, wherein the predicted versus observed AUC, C max, and t max were within 0.90 to 1.20-fold difference. After scaling anatomy/physiology, protein binding, and clearance, the model showed satisfactory prediction performance for pediatric populations as predicted AUC were within the 1.50-fold range of the observed values. According to the application of PBPK model, we found that different intravenous doses should be given in children of different ages compared to a standard 0.1 mg/kg in adults, while a progressive increasing dose with age growth following oral administration is recommended for children., Conclusions: The current example provides the opportunity for using the PBPK model to guide dose adjustment of oxycodone in the design of future pediatric clinical studies.

Oilseed rape (Brassica napus) has great potential for phytoremediation of cadmium (Cd)-polluted soils due to its large plant biomass production and strong metal accumulation. Enhanced plant Cd resistance (PCR) is a crucial prerequisite for phytoremediation through hyper-accumulation of excess Cd. However, the complexity of the allotetraploid genome of rapeseed hinders our understanding of PCR. To explore rapeseed Cd-resistance mechanisms, we examined two genotypes, 'ZS11' (Cd-resistant) and 'W10' (Cd-sensitive), that exhibit contrasting PCR while having similar tissue Cd concentrations, and characterized their different fingerprints in terms of plant morphophysiology (electron microscopy), ion abundance (inductively coupled plasma mass spectrometry), DNA variation (whole-genome resequencing), transcriptomics (high-throughput mRNA sequencing), and metabolomics (ultra-high performance liquid chromatography-mass spectrometry). Fine isolation of cell components combined with ionomics revealed that more Cd accumulated in the shoot vacuoles and root pectins of the resistant genotype than in the sensitive one. Genome and transcriptome sequencing identified numerous DNA variants and differentially expressed genes involved in pectin modification, ion binding, and compartmentalization. Transcriptomics-assisted gene co-expression networks characterized BnaCn.ABCC3 and BnaA8.PME3 as the central members involved in the determination of rapeseed PCR. High-resolution metabolic profiles revealed greater accumulation of shoot Cd chelates, and stronger biosynthesis and higher demethylation of root pectins in the resistant genotype than in the sensitive one. Our comprehensive examination using a multiomics approach has greatly improved our understanding of the role of subcellular reallocation of Cd in the determination of PCR., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Trifluoromethyl trifluoromethanesulfonate has proved to be an excellent reservoir of difluorophosgene and a promising click ligation for amines in the preparation of urea derivatives, heterocycles, and carbamoyl fluorides under metal- and additive-free conditions. The reactions are rapid, efficient, selective, and versatile, and can be performed in benign solvents, giving products in excellent yields with minimal efforts for purification. The characteristics of the reactions meet the requirements of a click reaction. The use of trifluoromethyl trifluoromethanesulfonate as a click reagent is advantageous over other "CO" sources (e.g., TsOCF 3 , PhCO 2 CF 3 , CsOCF 3 , AgOCF 3 , and triphosgene) because this reagent is readily accessible; easy to scale up; and highly reactive, even under metal- and additive-free conditions. It is anticipated that CF 3 SO 3 CF 3 will be increasingly as important as SO 2 F 2 as a click agent in future drug design and development., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The transmembrane transport of NO 3 - and Cd 2+ into plant cell vacuoles relies on the energy from their tonoplast proton pumps, V-ATPase and V-PPase. If the activity of these pumps is reduced, it results in less NO 3 - and Cd 2+ being transported into the vacuoles, which contributes to better nitrogen use efficiency (NUE) and lower Cd 2+ tolerance in plants. The physiological mechanisms that regulate the balance between NUE and Cd 2+ tolerance remain unknown. In our study, two Brassica napus genotypes with differential NUEs, xiangyou 15 and 814, and Atclca-2 mutant and AtCAX4 over-expression line (AtCAX4-OE) of Arabidopsis thaliana, were used to investigate Cd 2+ stress responses. We found that the Brassica napus genotype, with higher NUE, was more sensitive to Cd 2+ stress. The AtCAX4-OE mutant, with higher Cd 2+ vacuolar sequestration capacity (VSC), limited NO 3 - sequestration into root vacuoles and promoted NUE. Atclca-2 mutants, with decreased NO 3 - VSC, enhanced Cd 2+ sequestration into root vacuoles and conferred greater Cd 2+ tolerance than the WT. This may be due to the competition between Cd 2+ andNO 3 - in the vacuoles for the energy provided by V-ATPase and V-PPase. Regulating the balance between Cd 2+ and NO 3 - vacuolar accumulation by inhibiting the activity of CLCa transporter and increasing the activity of CAX4 transporter will simultaneously enhance both the NUE and Cd 2+ tolerance of Brassica napus, essential for improving its Cd 2+ phytoremediation potential., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The Chloride Channel (CLC) gene family is reported to be involved in vacuolar nitrate (NO3-) transport. Nitrate distribution to the cytoplasm is beneficial for enhancing NO3- assimilation and plays an important role in the regulation of nitrogen (N) use efficiency (NUE). In this study, genomic information, high-throughput transcriptional profiles, and gene co-expression analysis were integrated to identify the CLCs (BnaCLCs) in Brassica napus. The decreased NO3- concentration in the clca-2 mutant up-regulated the activities of nitrate reductase and glutamine synthetase, contributing to increase N assimilation and higher NUE in Arabidopsis thaliana. The genome-wide identification of 22BnaCLC genes experienced strong purifying selection. Segmental duplication was the major driving force in the expansion of the BnaCLC gene family. The most abundant cis-acting regulatory elements in the gene promoters, including DNA-binding One Zinc Finger, W-box, MYB, and GATA-box, might be involved in the transcriptional regulation of BnaCLCs expression. High-throughput transcriptional profiles and quantitative real-time PCR results showed that BnaCLCs responded differentially to distinct NO3- regimes. Transcriptomics-assisted gene co-expression network analysis identified BnaA7.CLCa-3 as the core member of the BnaCLC family, and this gene might play a central role in vacuolar NO3- transport in crops. The BnaCLC members also showed distinct expression patterns under phosphate depletion and cadmium toxicity. Taken together, our results provide comprehensive insights into the vacuolar BnaCLCs and establish baseline information for future studies on BnaCLCs-mediated vacuolar NO3- storage and its effect on NUE., Competing Interests: The authors have declared that no competing interests exist.

Background: Nitrogen (N) is a macronutrient that is essential for optimal plant growth and seed yield. Allotetraploid rapeseed (A n A n C n C n , 2n = 4x = 38) has a higher requirement for N fertilizers whereas exhibiting a lower N use efficiency (NUE) than cereal crops. N limitation adaptation (NLA) is pivotal for enhancing crop NUE and reducing N fertilizer use in yield production. Therefore, revealing the genetic and molecular mechanisms underlying NLA is urgent for the genetic improvement of NUE in rapeseed and other crop species with complex genomes., Results: In this study, we integrated physiologic, genomic and transcriptomic analyses to comprehensively characterize the adaptive strategies of oilseed rape to N limitation stresses. Under N limitations, we detected accumulated anthocyanin, reduced nitrate (NO 3 - ) and total N concentrations, and enhanced glutamine synthetase activity in the N-starved rapeseed plants. High-throughput transcriptomics revealed that the pathways associated with N metabolism and carbon fixation were highly over-represented. The expression of the genes that were involved in efficient N uptake, translocation, remobilization and assimilation was significantly altered. Genome-wide identification and molecular characterization of the microR827-NLA1-NRT1.7 regulatory circuit indicated the crucial role of the ubiquitin-mediated post-translational pathway in the regulation of rapeseed NLA. Transcriptional analysis of the module genes revealed their significant functional divergence in response to N limitations between allotetraploid rapeseed and the model Arabidopsis. Association analysis in a rapeseed panel comprising 102 genotypes revealed that BnaC5.NLA1 expression was closely correlated with the rapeseed low-N tolerance., Conclusions: We identified the physiologic and genome-wide transcriptional responses of oilseed rape to N limitation stresses, and characterized the global members of the BnamiR827-BnaNLA1s-BnaNRT1.7s regulatory circuit. The transcriptomics-assisted gene co-expression network analysis accelerates the rapid identification of central members within large gene families of plant species with complex genomes. These findings would enhance our comprehensive understanding of the physiologic responses, genomic adaptation and transcriptomic alterations of oilseed rape to N limitations and provide central gene resources for the genetic improvement of crop NLA and NUE.

Four unprecedented decanuclear heterometallic [Ln2CoII4CoIII4] clusters based on a diethanolamine ligand (H2dea), namely [Eu2CoII4CoIII4(dea)8(HCOO)4(OH)2(Cl)2(CH3OH)2]Cl2·4CH3OH·2H2O (1), [Gd2CoII4CoIII4(dea)8(HCOO)4(OH)2(Cl)2(CH3OH)2]Cl2·4CH3OH·2H2O (2), [Tb2CoII4CoIII4(dea)8(HCOO)4(OH)2(Cl)2(CH3OH)2]Cl2·2CH3OH·4H2O (3) and [Dy2CoII4CoIII4(dea)8(HCOO)4(OH)2(Cl)2(CH3OH)2]Cl2·2CH3OH·4H2O (4) were synthesized through a facile solution method. Single-crystal X-ray diffraction analyses reveal that complexes 1-4 consist of a [Ln2CoII4CoIII4] core, which is constructed by bridging a quasi-double cuboidal [Ln2CoII2CoIII2] core with two [CoIICoIII] units. Electrospray ionization mass spectrometry (ESI-MS) using methanol solution reveals that complexes 1-4 are stable in the solution, and the clusters undergo three different substitution reactions (Cl- replaced by OH-, OH- replaced by CH3O- and HCOO- replaced by OH-/CH3O-) at the same time in the ionization state. Magnetic susceptibilities reveal ferromagnetic couplings within complexes 3 and 4, and the magnetocaloric effect (MCE) for 2 was also evaluated and the maximum entropy change (-ΔSm) value reaches 16.3 J kg-1 K-1 at about 3 K and 5 T.