Synthesis of 1,3-Enynes by Iron-Catalyzed Propargylic C-H Functionalization: An Alkyne Analogue for the Eschenmoser Methenylation.

A two-step protocol for the conversion of alkyl-substituted alkynes to 1,3-enynes is reported. In this α-methenylation process, an iron-catalyzed propargylic C-H functionalization delivers tetramethylpiperidine-derived homopropargylic amines which undergo facile Cope elimination upon N-oxidation to afford the enyne products. A range of aryl alkyl and dialkyl acetylenes were found to be suitable substrates for this process, which constitutes an alkyne analogue for the Eschenmoser methenylation of carbonyl derivatives. In addition, a new bench-stable precatalyst for iron-catalyzed propargylic C-H functionalization is reported.

GLP-1 in hypothalamic paraventricular nucleus promotes sympathetic activation and hypertension.

Glucagon-like peptide-1 (GLP-1) and its analogs are widely used for treatment of diabetes. Paraventricular nucleus (PVN) is crucial for regulating cardiovascular activity. This study aims to determine the roles of GLP-1 and its receptors (GLP-1R) in PVN in regulating sympathetic outflow and blood pressure. Experiments were carried out in male normotensive rats and spontaneously hypertensive rats (SHR). Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. GLP-1 and GLP-1R expression was present in the PVN. PVN microinjection of GLP-1R agonist recombinant human GLP-1 (rhGLP-1) or EX-4 increased RSNA and MAP, which were prevented by GLP-1R antagonist EX9-39 or GLP-1R antagonist 1, superoxide scavenger tempol, antioxidant N-acetylcysteine, NADPH oxidase inhibitor apocynin, adenylyl cyclase inhibitor SQ22536 or protein kinase A (PKA) inhibitor H89. PVN microinjection of rhGLP-1 increased superoxide production, NADPH oxidase activity, cAMP level, adenylyl cyclase and PKA activity, which were prevented by SQ22536 or H89. GLP-1 and GLP-1R were upregulated in the PVN of SHR. PVN microinjection of GLP-1 agonist increased RSNA and MAP in both WKY and SHR, but GLP-1 antagonists caused greater effects in reducing RSNA and MAP in SHR than in WKY. The increased superoxide production and NADPH oxidase activity in the PVN of SHR were augmented by GLP-1R agonists, but attenuated by GLP-1R antagonists. These results indicate that activation of GLP-1R in PVN increased sympathetic outflow and blood pressure via cAMP-PKA-mediated NADPH oxidase activation and subsequent superoxide production. GLP-1 and GLP-1R upregulation in the PVN partially contribute to sympathetic overactivity and hypertension.Significance Statement Activation of GLP-1 receptors in paraventricular nucleus (PVN) increases sympathetic activity and blood pressure, which are mediated by cAMP-PKA-NADPH oxidase-superoxide production. Intervention of GLP-1 receptors in the PVN may play beneficial roles in attenuating sympathetic overactivity and hypertension. The central effects may have a major impact during GLP-1 receptor agonist therapy in patients with hypertension.

The association of metabolic syndrome scores trajectory patterns with risk of all cancer types.

BACKGROUND: Metabolic syndrome (MetS) elevates cancer risk. However, a single MetS assessment does not fully reveal the long-term association with cancer. Inflammation, alongside MetS, could synergistically expedite both the onset and advancement of cancer. This study aims to investigate MetS score trajectories and cancer risk in a large, prospective cohort study. METHODS: The authors prospectively examined the relationship between MetS score trajectory patterns and new-onset cancer in 44,115 participants. Latent mixture modeling was used to identify the MetS score trajectories. Cox proportional hazards regression models were used to evaluate the association between MetS score trajectory patterns and the risk of overall and site-specific cancers. RESULTS: Four MetS score trajectory patterns were identified: low-stable (n = 4657), moderate-low (n = 18,018), moderate-high (n = 18,288), and elevated-increasing (n = 3152). Compared to participants with a low-stable trajectory pattern, the elevated-increasing trajectory pattern was associated with an elevated risk of overall (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.04-1.55), breast (HR, 2.11; 95% CI, 1.04-4.34), endometrial (HR, 3.33; 95% CI, 1.16-6.77), kidney (HR, 4.52; 95% CI, 1.17-10.48), colorectal (HR, 2.54; 95% CI, 1.27-5.09), and liver (HR, 1.61; 95% CI, 1.09-4.57) cancers. Among participants with chronic inflammation (C-reactive protein levels ≥3 mg/L), the elevated-increasing trajectory pattern was significantly associated with subsequent breast, endometrial, colorectal, and liver cancers. CONCLUSIONS: Trajectories of MetS scores are associated with the occurrence of cancers, especially breast, endometrial, kidney, colorectal, and liver cancers, emphasizing the importance of long-term monitoring and evaluation of MetS. PLAIN LANGUAGE SUMMARY: The association between long-term elevated metabolic syndrome (MetS) scores and a heightened risk of various cancers is a pivotal finding of our study. Our research further indicates that individuals with MetS, particularly when coupled with chronic inflammation, are at an increased risk of cancer. We propose that sustained monitoring and management of MetS could be beneficial in reducing cancer risk.

Enantioselective and Regiodivergent Synthesis of Propargyl- and Allenylsilanes through Catalytic Propargylic C-H Deprotonation.

We report a highly enantioselective intermolecular C-H bond silylation catalyzed by a phosphoramidite-ligated iridium catalyst. Under reagent-controlled protocols, propargylsilanes resulting from C(sp3)-H functionalization, as well the regioisomeric and synthetically versatile allenylsilanes, could be obtained with excellent levels of enantioselectivity and good to excellent control of propargyl/allenyl selectivity. In the case of unsymmetrical dialkyl acetylenes, good to excellent selectivity for functionalization at the less-hindered site was also observed. A variety of electrophilic silyl sources (R3SiOTf and R3SiNTf2), either commercial or in situ-generated, were used as the silylation reagents, and a broad range of simple and functionalized alkynes, including aryl alkyl acetylenes, dialkyl acetylenes, 1,3-enynes, and drug derivatives were successfully employed as substrates. Detailed mechanistic experiments and DFT calculations suggest that an η3-propargyl/allenyl Ir intermediate is generated upon π-complexation-assisted deprotonation and undergoes outer-sphere attack by the electrophilic silylating reagent to give propargylic silanes, with the latter step identified as the enantiodetermining step.

A Smartphone Application-Based Remote Rehabilitation System for Post-Total Knee Arthroplasty Rehabilitation: A Randomized Controlled Trial.

BACKGROUND: Remote rehabilitation after total knee arthroplasty has gradually gained popularity in recent years. This study aimed to determine whether smartphone application-based remote rehabilitation could outperform home-based rehabilitation and outpatient guidance in terms of 12-week outcomes following primary unilateral total knee arthroplasty. METHODS: Patients who underwent primary unilateral total knee arthroplasty were recruited and randomly divided into a telerehabilitation group and a control group. A total of 100 patients were examined, with 50 each assigned to the telerehabilitation and control groups. In the telerehabilitation group, a telerehabilitation application was installed on the smartphones of the participants to allow postdischarge guidance. The primary outcomes were knee range of motion (ROM) at 12 weeks postoperatively. Secondary outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index, Knee Society Score, The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), Five Times Sit-to-Stand Test (5xSST), Single-Leg Stance Test (SLST), satisfaction, rehabilitation costs, complication rate, and 90-day readmission rate. All outcomes were collected at 2, 6, and 12 weeks after surgery. RESULTS: At 12 weeks postoperatively, the telerehabilitation patients significantly outperformed the controls in terms of knee ROM (124 ± 8.7 versus 119 ± 5.5 P = .01), SF-36 (physiological function) (61.5 ± 20.3 versus 45.5 ± 18.1 P = .000), SF-36 (role-physical) (49.3 ± 41.5 versus 27.7 ± 28.9 P = .012), SLST (13.0 ± 9.1 versus 9.1 ± 5.9 P = .026), and 5xSST (17.7 ± 4.3 versus 19.4 ± 3.5 P = .043). No significant differences were found between groups in the Western Ontario and McMaster Universities Osteoarthritis Index score, Knee Society Score, rehabilitation costs, 90-day readmission rate, or incidence of adverse events. CONCLUSION: Our study showed that smartphone app-based remote rehabilitation worked better than home-based rehabilitation with outpatient guidance in terms of short-term results in ROM, SLST, and 5xSST.

Effectiveness of Acupoint Application in Patients with Pharyngeal Pain: Evidence from CHUNBO, A Prospective Real-World Study.

OBJECTIVE: To assess the outcomes after acupoint application in patients with pharyngeal pain in a real-world settings, and analyze the characteristics of effective population and prescription characteristics of acupoint application. METHODS: Based on CHUNBO platform, patients with pharyngeal pain who were candidates for acupoint application on the basis of physician-evaluation, were enrolled in a nationwide, prospective, 69-week multicenter observational study from August 2020 to February 2022. Propensity score matching (PSM) was used to match the confounding factors and the association rules were used to analyze the characteristics of effective population and prescription characteristics of acupoint application. Outcome assessments included the disappearance rate of pharyngeal pain (within 3, 7, and 14 days), disappearance time of pharyngeal pain, as well as adverse events. RESULTS: Of 7,699 enrolled participants, 6,693 (86.9%) received acupoint application and 1,450 (21.7%) with non-acupoint application. After PSM, there were 1,004 patients each in the application group (AG) and non-application group (NAG). The disappearance rate of pharyngeal pain in the AG at 3, 7, and 14 days were all higher than those in the NAG (P<0.05). The disappearance time of pharyngeal pain in the AG were shorter than that in the NAG (logrank P<0.001, hazard ratio=1.51, 95% confidence interval: 1.41-1.63). The median age of effective cases was 4 years, mainly 3-6 years old (40.21%). The disappearance rate of pharyngeal pain in the application group with tonsil diseases was 2.19 times higher than that in the NAG (P<0.05). The commonly used acupoints for the effective cases were Tiantu (RN 22), Shenque (RN 8) and Dazhui (DU 14). The commonly used herbs for the effective cases were Natrii sulfas, Radix et Rhizoma Rhei, and Herba Ephedrae. Among them, Natrii sulfas was applied to RN 8 most frequently (support 84.39%). A total of 1,324 (17.2%) patients experienced AEs, and mainly occurred in the AG, with significant difference in the incidence of AEs between goups (P<0.05). All AEs reported were the first grade, and the average regression days of AEs was 2.8 days. CONCLUSIONS: Acupoint application in patients with pharyngeal pain resulted in improved effective rate and shortened duration, especially children aged 3-6 years old, and those with tonsil diseases. Acupoint of RN 22, RN 8 and DU 14, Natrii sulfas, Radix et Rhizoma Rhei, and Herba Ephedrae were the most commonly used herbs in the treatment of pharyngeal pain.

Association of the age of onset of metabolic syndrome with the risk of all cancer types.

BACKGROUND: The association between the age at onset of metabolic syndrome and cancer risk remains unknown. This study explored the association between age at metabolic syndrome onset and the risk of overall and site-specific cancer incidence. METHODS: This study included 31,688 participants with new-onset metabolic syndrome and 31,688 participants matched according to sex, age (±1 y), and examination year among the 179,328 participants who underwent Kailuan health examinations from 2006 to 2017 in Tangshan, China. Weighted Cox regression was used to calculate the hazard ratios and 95% confidence intervals of new-onset metabolic syndrome for overall and site-specific cancer incidence across age groups. Population-attributable risk proportions were used to estimate the number of cases that could be prevented by eliminating the risk factors from the population. RESULTS: During an average follow-up period of 10.22 y, we identified 2,710 cases of cancer and 4,218 deaths that occurred before the diagnosis of cancer. With an increase in metabolic syndrome onset age, the hazards of overall cancer incidence were gradually attenuated. The average hazard ratios (95% confidence intervals) of overall cancer were 1.94 (1.25-2.99) for metabolic syndrome onset age <45 year old, 1.41 (1.15-1.71) for age 45-54 years old, 1.38 (1.11-1.73) for age 55-64 years old, and 1.07 (0.89-1.28) for age ≥65 years old, respectively (p for interaction = 0.005). Similar results were obtained for colorectal, liver, and breast cancers in the site-specific analysis. CONCLUSIONS: New-onset metabolic syndrome was associated with a higher risk of overall cancer and incidence of several types of cancer, and the associations were stronger with a younger age of onset. TRIAL REGISTRATION: Kailuan Study, ChiCTR2000029767 (Registered February 12, 2020, https://www.chictr.org.cn/showprojEN.html?proj=48316).

Template Synthesis to Solve the Unreachable Ortho C-H Functionalization Reaction of Aryl Iodide.

This report describes the use of a simple Pd/NBE catalytic system to achieve ortho C-H oxylation and phosphonylation and other functionalizations of aryl iodide through templated conversion reactions. Dimethylamine is introduced in the ortho-site of aryl iodide through C-H amination, and aryl dimethylamine is quickly converted to methyl quaternary ammonium salt precipitation. Methyl quaternary ammonium salt avoids Hofmann elimination in subsequent functionalization. This method solves various ortho functionalization reactions of aryl iodide that have not been achieved for a long time in the field of Pd/NBE chemistry indirectly.

Flexible Block Copolymer Metamaterials Featuring Hollow Ordered Nanonetworks with Ultra-High Porosity and Surface-To-Volume Ratio.

By utilizing bicontinuous and nanoporous ordered nanonetworks, such as double gyroid (DG) and double diamond (DD), metamaterials with exceptional optical and mechanical properties can be fabricated through the templating synthesis of functional materials. However, the volume fraction range of DG in block copolymers is significantly narrow, making it unable to vary its porosity and surface-to-volume ratio. Here, the theoretically limited structural volume of the DG phase in coil-coil copolymers is overcome by enlarging the conformational asymmetry through the association of mesogens, providing fast access to achieving flexible structured materials of ultra-high porosities. The new materials design, dual-extractable nanocomposite, is created by incorporating a photodegradable block with a solvent-extractable mesogen (m) into an accepting block, resulting in a new hollow gyroid (HG) with the largely increased surface-to-volume ratio and porosity of 77 vol%. The lightweight HG exhibits a low refractive index of 1.11 and a very high specific reduced modulus, almost two times that of the typical negative gyroid (porosity≈53%) and three times that of the positive gyroid (porosity≈24%). This novel concept can significantly extend the DG phase window of block copolymers and the corresponding surface-to-volume ratio, being applicable for nanotemplate-synthesized nanomaterials with a great gain of mechanical, catalytic, and optoelectronic properties.

Connectivity Analysis of Adsorption Sites in Metal-Organic Frameworks for Facilitated Water Adsorption.

Metal-organic frameworks (MOFs) have recently drawn considerable attention as promising adsorbents to harvest atmospheric water. To achieve an efficient harvesting process, seeking MOFs that demonstrate sharp condensation behavior is the key. Given that the clustering of water molecules in MOFs should be driven by not only MOF-water interactions but also water-water interactions, the spatial arrangement of water adsorption sites in a MOF is therefore crucial. Specifically, this study demonstrates the critical role of continuous adsorption channels (CACs) in MOFs. Such CACs will enable water molecules to stay in proximity and in a continuous manner, thus promoting the formation of hydrogen bonds and, consequently, the clustering of water molecules. We have developed an automatic algorithm to detect CACs based on the energy grid of host-guest interactions and applied the algorithm to more than 2000 diverse structures. The results show that more than 80% of the studied MOFs displaying water condensation at 298 K and 20% relative humidity predicted by Monte Carlo simulations indeed have CACs. The developments herein are anticipated to largely facilitate the future discovery of optimal adsorbents for water harvesting or water-adsorption-related applications in general. A Python-based code for detecting CACs in porous materials is also provided along with this article to employ this approach.

Stem Cells from Human Exfoliated Deciduous Teeth Alleviate High-Altitude Cerebral Oedema by Shifting Microglial M1/M2 Polarisation.

OBJECTIVE: To explore the high-efficiency and low-risk prevention and treatment strategies for stem cells from human exfoliated deciduous teeth (SHED) for high-altitude cerebral oedema. METHODS: A low-pressure and low-oxygen tank mimicking high-altitude conditions was used to establish the high-altitude cerebral oedema animal model. The preventive effects of SHED for cerebral oedema were then evaluated by haematoxylin and eosin (H&E) and histological staining. In vitro, SHED was co-cultured with BV-2 to analyse the effects of SHED by western blot and immunofluorescence staining. RESULTS: SHED can prevent and treat cerebral oedema in a high altitude rat animal model. Mechanistically, SHED treatment can protect brain cells from apoptosis induced by high altitude condition. Moreover, SHED treatment can inhibit M1-type polarisation and promote M2-type polarisation of microglia cells via the suppression of hypoxia inducible factor (HIF)- 1α-mediated extracellular signal-regulated kinase (ERK) signalling activated in high altitude condition. CONCLUSION: SHED treatment can relieve high-altitude cerebral oedema via inhibiting HIF- 1α-mediated ERK signalling, which indicates that SHED is a promising alternative strategy to prevent and treat high-altitude cerebral oedema.

Thin jets underlie the solar wind.

Solar Orbiter images reveal widespread magnetic plasma jets at the roots of the solar wind.

THz enantiomers of drugs recognized by the polarization enhancement of gold nanoparticles on an asymmetric metasurface.

Chirality plays an important role in biological processes, and enantiomers often possess similar physical properties and different physiological functions. Thus, chiral detection of enantiomers has become a hot topic in recent years, and methods to enhance chiral molecular recognition are in urgent demand. In this work, a polarization detection method was used for different chiral drugs based on a specially designed metasurface composed of asymmetric double-opened rings and the surface enhancement effect of gold nanoparticles (GNPs). The experiment results show that the frequency shifts caused by the nearfield interaction of the metasurface and biomolecules have been significantly improved by GNPs, and both the limit of detection and detection precision of the metasurface can reach the 10-5 g ml-1 level. Moreover, the polarization sensing characterized by right circular polarization (RCP), the polarization elliptical angle (PEA), and the polarization rotation angle (PRA) shows that the enantiomers of three drugs can be distinguished, especially using the PEA spectrum; the maximum difference between enantiomers is over 30° with a precision of 6.6 × 10-7 g mL-1. Our THz polarization sensing and the GNP enhancement method inspire an efficient strategy for the highly sensitive detection of enantiomers.

Post-extubation use of high-flow nasal oxygenation induces upper airway leak and intrathoracic sepsis after successful Bentall procedure: A case report.

RATIONALE: In recent few years, high-flow nasal oxygenation (HFNO) has been widely used for management of acute hypoxemic respiratory failure and during postextubation periods, including after endotracheal intubation general anesthesia (ETGA). However, HFNO generates positive pressure in the injured airway following removal of endotracheal tube may cause airway leaks. This is the first case report of severe airway leak syndrome following postextubation use of HFNO in surgical patients. PATIENT CONCERNS: This case report describes a 75-year-old female with critical aortic stenosis who underwent an emergency Bentall procedure. HFNO (flow rate of 45 L/min) was applied after weaning from mechanical ventilation and removal of the endotracheal tube. DIAGNOSES: At 6 hours after HFNO application, subcutaneous emphysema in the neck bilaterally and face was noted, and the emphysema extended into the supraclavicular regions. INTERVENTIONS: The HFNO cannula was removed soon after and the patient was re-intubated with an endotracheal tube the following day due to progressive respiratory insufficiency. Unfortunately, the patient general condition deteriorated, as the subcutaneous air collections progressed into deep tissue infections of the neck, mediastinal abscesses, and left-sided empyema. Patient received surgical interventions repeatedly to drain the mediastinal abscess and empiric antimicrobial therapy was given. OUTCOMES: The patient passed away about 2 months later due to uncontrollable sepsis. LESSONS: Air leaks in the upper airway can occur during the use of post-extubation HFNO use, and the resulting subcutaneous emphysema can progress to severe intrathoracic infections in surgical patients who have a sternotomy wound. Therefore, HFNO-induced subcutaneous emphysema should be treated more aggressively in open thoracic or sternotomy surgeries to prevent the development of intrathoracic sepsis.

[Network Meta-analysis of oral Chinese patent medicine in adjuvant treatment of rotavirus gastroenteritis in children].

This study aimed to evaluate the efficacy and safety of various oral Chinese patent medicines in the adjuvant treatment of rotavirus gastroenteritis(RVGE) in children based on network Meta-analysis. Randomized controlled trial(RCT) of oral Chinese patent medicine in the adjuvant treatment of RVGE in children was retrieved from the databases such as CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science from database inception to October 22, 2022. The quality of the included RCT was evaluated according to the Cochrane risk-of-bias tool, and the data were analyzed by RevMan 5.4 and Stata 16 software. Sixty-three RCTs were included, with 11 oral Chinese patent medicines involved, including Xingpi Yanger Granules, Weichang'an Pills, Qiuxieling Mixture, Erxieting Granules, and Changyanning Granules/Syrup. The results of the network Meta-analysis showed that in terms of clinical total effective rate, the top 3 optimal interventions were Changyanning Granules/Syrup, Xiaoer Guangpo Zhixie Oral Liquid, and Xiaoer Shuangjie Zhixie Granules combined with conventional western medicine. In terms of the anti-diarrheal time, the top 3 optimal interventions were Shenling Baizhu Granules, Qiuxieling Mixture, and Shuangling Zhixie Oral Liquid combined with conventional western medicine. In terms of the antiemetic time, the top 3 optimal interventions were Changyanning Granules/Syrup, Xingpi Yanger Granules, and Xiaoer Shuangjie Zhixie Granules combined with conventional western medicine. In terms of the antipyretic time, the top 3 optimal interventions were Shenling Baizhu Granules, Xiaoer Shuangjie Zhixie Granules, and Qiuxieling Mixture combined with conventional western medicine. In terms of the negative conversion rate of rotavirus, the top 3 optimal interventions were Xingpi Yanger Granules, Erxieting Granules, and Cangling Zhixie Oral Liquid combined with conventional western medicine. In terms of reducing creatine kinase isoenzyme MB(CK-MB) level, the top 3 optimal interventions were Weichang'an Pills, Xingpi Yanger Granules, and Xiaoer Shuangjie Zhixie Granules combined with conventional western medicine. In terms of adverse reactions, no se-rious adverse reactions were reported in all studies. Oral Chinese patent medicines in the adjuvant treatment of children with RVGE have their own advantages, Specifically, Changyanning Granules/Syrup + conventional western medicine focuses on improving the clinical total effective rate and shortening the antiemetic time, Shenling Baizhu Granules + conventional western medicine on shortening the anti-diarrheal time and antipyretic time, Xingpi Yanger Granules + conventional western medicine on improving the negative conversion rate of rotavirus, and Weichang'an Pills + conventional western medicine on reducing the CK-MB level. Limited by the quantity and quality of literature included in this study, the results need to be verified by high-quality RCT with a larger sample size.

Synthesis of 1,1-Disubstituted Allenylic Silyl Ethers Through Iron-Catalyzed Regioselective C(sp2)─H Functionalization of Allenes.

We report a synthesis of allenylic silyl ethers through iron-catalyzed functionalization of the C(sp2)─H bonds of monosubstituted alkylallenes. In the presence of a cyclopentadienyliron dicarbonyl based catalyst and triisopropylsilyl triflate as a silylation agent, a variety of aryl aldehydes were suitable coupling partners in this transformation, furnishing a collection of 1,1-disubstituted allenylic triisopropylsilyl ethers as products in moderate to excellent yields as a single regioisomer. Lithium bistriflimide was identified as a critical additive in this transformation. The optimized protocol was scalable, and the products were amenable to further transformation to give a number of unsaturated, polyfunctional derivatives.

Two novel fluorescent probes based on quinolinone for continuous recognition of Al3+ and ClO.

On the basis of classical Schiff base reaction, two novel and efficient fluorescent probes (DQNS, DQNS1) were designed and synthesized by introducing Schiff base structure into dis-quinolinone unit for structural modification, which can be used to detect Al3+ and ClO-. Because the power supply capacity of H is weaker than that of methoxy, DQNS shows better optical performance: a large Stokes Shift (132 nm), identify Al3+ and ClO- with high sensitivity and selectivity, low detection limit (29.8 nM and 25 nM) and fast response time (10 min and 10 s). Through the working curve and NMR titration experiment, the recognition mechanism of Al3+ and ClO- (PET and ICT) probes are confirmed. Meanwhile, it is speculated that the probe has continuity for the detection of Al3+ and ClO-. Furthermore, DQNS detection of Al3+ and ClO- was applied to real water samples and living cell imaging.

A systematic analysis of genotype-phenotype associations with PLA2G6.

BACKGROUND: PLA2G6-associated neurodegeneration (PLAN) can be categorized into infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (aNAD), neurodegeneration with brain iron accumulation (NBIA), and early-onset parkinsonism (EOP). OBJECTIVES: To determine the genotype-phenotype association in PLAN. METHODS: "PLA2G6" or "PARK14" or "phospholipase A2 group VI" or "iPLA2ß" were searched across MEDLINE from June 23, 1997, to March 1, 2023. A total of 391 patients were identified, and 340 patients of them were finally included in the assessment. RESULTS: The loss of function (LOF) mutation ratios were significantly different (p < 0.001), highest in INAD, followed by NBIA, aNAD, and EOP. Four ensemble scores (i.e., BayesDel, VARITY, ClinPred, and MetaRNN) were assessed to predict the deleteriousness of missense mutations and demonstrated significant differences (p < 0.001). Binary logistic regression analyses demonstrated that LOF mutations were independently associated with brain iron accumulation (p = 0.006) and ataxia (p = 0.025). CONCLUSIONS: LOF or more deleterious missense mutations are more likely to promote the development of serious phenotype of PLAN, and LOF mutations are independently associated with brain iron accumulation and ataxia.

Exposure to negative foreign COVID-19 news predicts lower support for immigration policy in China.

We present a framework for studying the spillover effect of negative foreign COVID-19 news on attitudes towards immigration. Our framework proposes that exposure to negative COVID-19 news from foreign countries can activate negative associations with foreigners, reduce positive attitudes towards them, and increase perceived threat, ultimately leading to decreased support for immigration. We conducted three studies to test this framework. Study 1 found that exposure to negative COVID-19 news about a foreign country increased negative valence associations with that country. Study 2 showed that exposure to more negative COVID-19 news about foreign countries was associated with lower acceptance of immigration policies in real life. Study 3 replicated the spillover effect of negative news exposure using a scenario manipulation. The effects of negative news exposure on immigration policy acceptance in both Studies 2 and 3 were mediated by changes in foreigner attitudes and intergroup threat. Our results demonstrate the important spillover effect of negative foreign COVID-19 news exposure on immigration attitudes and highlight the association perspective as a foundation for understanding attitude changes during the COVID-19 pandemic.