Altered intra- and inter-network brain functional connectivity associated with prolonged screen time in pre-school children with autism spectrum disorder.

Prolonged screen time (ST) has adverse effects on autistic characteristics and language development. However, the mechanisms underlying the effects of prolonged ST on the neurodevelopment of children with autism spectrum disorder (ASD) remain unclear. Neuroimaging technology may help to further explain the role of prolonged ST in individuals with ASD. This study included 164 cases, all cases were divided into low-dose ST exposure (LDE group 108 cases) and high-dose ST exposure (HDE group 56 cases) based on the average ST of all subjects. Spatial independent component analysis (ICA) was used to identify resting state networks (RSNs) and investigate intra- and inter-network alterations in ASD children with prolonged ST. We found that the total Childhood Autism Rating Scale (CARS) scores in the HDE group were significantly higher than those in the LDE group (36.2 ± 3.1 vs. 34.6 ± 3.9, p = 0.008). In addition, the developmental quotient (DQ) of hearing and language in the HDE group were significantly lower than those in the LDE group (31.5 ± 13.1 vs. 42.5 ± 18.5, p < 0.001). A total of 13 independent components (ICs) were identified. Between-group comparison revealed that the HDE group exhibited decreased functional connectivity (FC) in the left precuneus (PCUN) of the default mode network (DMN), the right middle temporal gyrus (MTG) of the executive control network (ECN), and the right median cingulate and paracingulate gyri (MCG) of the attention network (ATN), compared with the LDE group. Additionally, there was an increase in FC in the right orbital part of the middle frontal gyrus (ORBmid) of the salience network (SAN), compared with the LDE group. The inter-network analysis revealed increased FC between the visual network (VN) and basal ganglia (BG) and decreased FC between the sensorimotor network (SMN) and DMN, SMN and ATN, SMN and auditory network (AUN), and DMN and SAN in the HDE group, compared with the LDE group. There was a significant negative correlation between altered FC values in MTG and total CARS scores in subjects (r = - 0.18, p = 0.018).  Conclusion: ASD children with prolonged ST often exhibit lower DQ of language development and more severe autistic characteristics. The alteration of intra- and inter-network FC may be a key neuroimaging feature of the effect of prolonged ST on neurodevelopment in ASD children.  Clinical trial registration: ChiCTR2100051141. What is Known: • Prolonged ST has adverse effects on autistic characteristics and language development. • Neuroimaging technology may help to further explain the role of prolonged ST in ASD. What is New: • This is the first study to explore the impact of ST on intra- and inter-network FC in children with ASD. • ASD children with prolonged ST have atypical changes in intra- and inter-brain network FC.

Overview of ectopic pancreas.

This editorial discusses the article written by Zheng et al that was published in the latest edition of the World Journal of Gastrointestinal Surgery. Our primary focus is on the causes, location, diagnosis, histological classification, and therapy of ectopic pancreas. Ectopic pancreas refers to the presence of pancreatic tissue that is situated in a location outside its usual anatomical placement, and is not connected to the normal pancreas in terms of blood supply or anatomical structure. Currently, the embryological origin of ectopic pancreas remains uncertain. The most prevalent form of ectopic pancreatic is gastric ectopic pancreas. Endoscopic ultrasonography examination can visualize the morphological characteristics of the ectopic pancreatic lesion and pinpoint its anatomical location. The histological categorization of ectopic pancreas evolves. Endoscopic treatment has been widely advocated in ectopic pancreas.

Parent-child interaction related to brain functional alterations and development outcomes in autism spectrum disorder: A study based on resting state-fMRI.

BACKGROUND: Limited study has investigated the influence of parent-child interaction on brain functional alterations and development outcomes of autism spectrum disorder (ASD) children. This pilot study aimed to explore the relationship between parent-child interaction, brain functional activities and development outcomes of ASD children. METHODS: and Procedures: 653 ASD with an average age of 41.06 ± 10.88 months and 102 typically developmental (TD) children with an average age of 44.35 ± 18.39 months were enrolled in this study, of whom 155 ASD completed brain rs-fMRI scans. The amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) measured using resting-state functional magnetic resonance imaging (rs-fMRI) data reflect local brain function. The parent-child interaction was assessed by the Chinese Parent-child Interaction Scale (CPCIS). Childhood Autism Rating Scale (CARS) and developmental quotient (DQ) indicated development outcomes. OUTCOMES AND RESULTS: Total CPCIS score was negatively correlated with CARS total score, and positively correlated with DQ. The frequency of parent-child interaction was negatively correlated with ALFF values in the left median cingulate and paracingulate gyri (DCG.L) and ReHo values in the right superior frontal gyrus, medial (SFGmed.R)(P < 0.05, FDR correction). ALFF values in the DCG.L and ReHo values in the SFGmed.R play complete mediating roles in the relationship between parent-child interaction and performance DQ. CONCLUSION AND IMPLICATIONS: This study suggest that parent-child interaction has an impact on autistic characteristics and DQ of ASD children. Local brain regions with functional abnormalities in the DCG.L and SFGmed.R may be a crucial factors affecting the performance development of ASD children with reduced parent-child interaction.

Unleashing the Potential of High-Capacity Anodes through an Interfacial Prelithiation Strategy.

The scalable development of an environmentally adaptive and homogeneous Li+ supplementary route remains a formidable challenge for the existing prelithiation technologies, restricting the full potential of high-capacity anodes. In this study, we present a moisture-tolerant interfacial prelithiation approach through casting a hydrophobic poly(vinylidene-co-hexafluoropropylene) membrane blended with a deep-lithiated alloy (Li22Si5@C/PVDF-HFP) onto Si based anodes. This strategy could not only extend to various high-capacity anode systems (SiOx@C, hard carbon) but also align with industrial roll-to-roll assembly processes. By carefully adjusting the thickness of the prelithiation layer, the densely packed Si@C electrode (4.5 mAh cm-2) exhibits significantly improved initial Coulombic efficiency until a close-to-unit value, as well as extreme moisture tolerance (60% relative humidity). Furthermore, it achieves more than 10-fold enhancement of ionic conductivity across the electrode. As pairing the prelithiated Si@C anode with the LiNi0.8Co0.1Mn0.1O2 cathode, the 2 Ah pouch-format prototype balances an energy density of ∼371 Wh kg-1 and an extreme power output of 2450 W kg-1 as well as 83.8% capacity retention for 1000 cycles. The combined operando phase tracking and spatial arrangement analysis of the intermediate alloy elucidate that the enhanced Li utilization derives from the gradient stress dissipation model upon a spontaneous Li+ redistribution process.

Short-term safety of inactivated SARS-Cov-2 vaccines in Chinese patients with central nervous system inflammatory demyelinating diseases.

Objective: This study aims to evaluate the short-term safety of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in Chinese patients with central nervous system inflammatory demyelinating diseases (CNS IDDs). Methods: A web-based survey was conducted among patients with CNS IDDs from April 15 to 19, 2022 in China. In total, 645 patients with CNS IDDs were identified, including 425 patients with multiple sclerosis (MS), 194 with neuromyelitis optica spectrum disorder (NMOSD), and 26 with other CNS IDDs. The questionnaire consisted of demographic data, clinical records, history of SARS-CoV-2 vaccination, and vaccination-related symptoms within one month after vaccination. The demographic data, clinical information, and relapse rates between vaccinated and non-vaccinated patients were compared. Results: Among 645 patients with CNS IDDs, 78 were vaccinated and 567 were non-vaccinated with the vaccination rate of 12.1 %. Compared to non-vaccinated group, a lower percentage of patients on DMDs therapy (41.0 % vs. 71.8 %, P < 0.001) and an increased proportion of patients with other vaccination in past 3 years (17.9 % vs. 4.8 %, P < 0.001) were observed in vaccinated group. Six patients experienced a relapse within 30 days of a vaccination. Additionally, vaccine-associated relapse rates in vaccinated patients did not significantly differ from these in non-vaccinated patients among 2020, 2021, and from January 1 to October 1, 2022. Conclusions: No increased risk of vaccination-associated relapses among Chinese patients with CNS IDDs indicated that inactivated SARS-CoV-2 vaccines appear to be safe for this population.

Bisphosphonate-incorporated coatings for orthopedic implants functionalization.

Bisphosphonates (BPs), the stable analogs of pyrophosphate, are well-known inhibitors of osteoclastogenesis to prevent osteoporotic bone loss and improve implant osseointegration in patients suffering from osteoporosis. Compared to systemic administration, BPs-incorporated coatings enable the direct delivery of BPs to the local area, which will precisely enhance osseointegration and bone repair without the systemic side effects. However, an elaborate and comprehensive review of BP coatings of implants is lacking. Herein, the cellular level (e.g., osteoclasts, osteocytes, osteoblasts, osteoclast precursors, and bone mesenchymal stem cells) and molecular biological regulatory mechanism of BPs in regulating bone homeostasis are overviewed systematically. Moreover, the currently available methods (e.g., chemical reaction, porous carriers, and organic material films) of BP coatings construction are outlined and summarized in detail. As one of the key directions, the latest advances of BP-coated implants to enhance bone repair and osseointegration in basic experiments and clinical trials are presented and critically evaluated. Finally, the challenges and prospects of BP coatings are also purposed, and it will open a new chapter in clinical translation for BP-coated implants.

Rituximab at lower dose for neuromyelitis optica spectrum disorder: a multicenter, open-label, self-controlled, prospective follow-up study.

Objective: To address a novel lower-dose rituximab (RTX) therapy strategy based on our clinical experience and assess its efficacy and safety in neuromyelitis optica spectrum disorder (NMOSD). Methods: A multicenter, open-label, self-controlled, prospective follow-up study. Totally, 108 NMOSD patients were enrolled and a lower-dose RTX strategy was applied including 100 mg weekly for 3 weeks and then reinfusions every 6 months. Annualized relapse rate (ARR), the expanded disability status scale (EDSS) score and length of spinal cord lesions were included to evaluate the efficacy. Side effects were recorded to assess the safety profile. Results: Of 108 patients, 80 (74.1%) initiated low-dose RTX therapy immediately after acute attack treatment and 33 (30.6%) initiated it after the first attack. During a median treatment period of 35.5 (22.0-48.8) months, significant decreases were observed in median ARR (1.1 [0.8-2.0] versus 0 [0-0.2], p < 0.001), EDSS score (3.5 [2.5-4.0] versus 2.0 [1.0-3.0], p < 0.001) and spinal cord lesion segments (5.0 [4.0-8.0] versus 3.0 [1.0-6.0], p < 0.001). The cumulative risk of relapses significantly decreased during the post- versus pre-RTX period (HR 0.238, 95%CI 0.160-0.356, p < 0.001) and on early therapy initiated within 24 months after disease onset versus delayed therapy (HR 0.506, 95%CI 0.258-0.994, p = 0.041). No serious side effects were recorded and all the subjects did not discontinue treatment due to RTX-related side effects. Conclusion: Our research provided evidence supporting the lower-dose RTX strategy in treating NMOSD and reopened the issues of optimal dosage and therapy initiation timing.

Integrated Transcriptome and Metabolome Analysis Revealed the Causal Agent of Primary Bud Necrosis in 'Summer Black' Grape.

Primary bud necrosis of grape buds is a physiological disorder that leads to decreased berry yield and has a catastrophic impact on the double cropping system in sub-tropical areas. The pathogenic mechanisms and potential solutions remain unknown. In this study, the progression and irreversibility patterns of primary bud necrosis in 'Summer Black' were examined via staining and transmission electron microscopy observation. Primary bud necrosis was initiated at 60 days after bud break and was characterized by plasmolysis, mitochondrial swelling, and severe damage to other organelles. To reveal the underlying regulatory networks, winter buds were collected during primary bud necrosis progression for integrated transcriptome and metabolome analysis. The accumulation of reactive oxygen species and subsequent signaling cascades disrupted the regulation systems for cellular protein quality. ROS cascade reactions were related to mitochondrial stress that can lead to mitochondrial dysfunction, lipid peroxidation causing damage to membrane structure, and endoplasmic reticulum stress leading to misfolded protein aggregates. All these factors ultimately resulted in primary bud necrosis. Visible tissue browning was associated with the oxidation and decreased levels of flavonoids during primary bud necrosis, while the products of polyunsaturated fatty acids and stilbenes exhibited an increasing trend, leading to a shift in carbon flow from flavonoids to stilbene. Increased ethylene may be closely related to primary bud necrosis, while auxin accelerated cell growth and alleviated necrosis by co-chaperone VvP23-regulated redistribution of auxin in meristem cells. Altogether, this study provides important clues for further study on primary bud necrosis.

Tectorigenin targets PKACα to promote GLUT4 expression in skeletal muscle and improve insulin resistance in vitro and in vivo.

The decreased expression and dysfunction of glucose transporter 4 (GLUT4), the insulin-responsive glucose transporter, are closely related to the occurrence of insulin resistance (IR). To improve the expression of GLUT4 may represent a promising strategy to prevent and treat IR and type 2 diabetes (T2DM). Here, we demonstrate that the natural compound tectorigenin (TG) enhances GLUT4 expression, glucose uptake and insulin responsiveness via activating AMP-activated protein kinase (AMPK)/myocyte enhancer factor 2 (MEF2) signaling in both normal and IR skeletal muscle cells and tissues. Accordingly, prophylactic and therapeutic uses of TG can significantly ameliorate IR and hyperglycemia in T2DM mice. Mechanistically, we identify protein kinase A catalytic subunit α (PKACα) as the target of TG to increase GLUT4 expression and TG-PKACα binding promotes the dissociation of PKACα from the regulatory subunits, leading to the activation of PKA/AMPK signaling. PKACα knockdown in local quadriceps muscles almost completely abolished the therapeutic effects of TG on IR and T2DM, as well as the enhancement on AMPK signaling and GLUT4 expression in skeletal muscle. This study supports TG as a new drug candidate to treat IR and its related diseases, but also enriches our knowledge of PKA signaling in glucose metabolism in skeletal muscle.

Defatted hempseed meal altered the metabolic profile of fermented yogurt and enhanced the ability to alleviate constipation in rats.

BACKGROUND: Hempseeds (Cannabis sativa L.) are rich in easily digestible proteins, fats, polyunsaturated fatty acids, and insoluble fiber and are of high nutritional value. Probiotics have been found to relieve constipation, which solves a health problem that constantly troubles a lot of people. Therefore, the changes in the metabolites of fermented yogurt with or without 10% defatted hempseed meal (10% SHY or 0% SHY respectively) were studied and their laxative effects were examined through animal experiments. RESULTS: Amino acids and peptides, terpene glycosides, carbohydrates, lineolic acids, and fatty acids were found to be the major contributors to the discrimination of the metabolic profile between 0% SHY and 10% SHY. The differentially accumulated metabolites may lead to the discrepancy in the yogurt's functionality. Animal experiments showed that the 10% SHY treatment prevented constipation by increasing feces number, fecal water content, and small intestinal transit rate and reducing inflammatory injury in loperamide-induced constipated rats. Further analysis of the gut microbiota revealed that 10% SHY gavage increased the relative abundances of the Lactobacillus, Allobaculum, Turicibacter, Oscillibacter, Ruminococcus, and Phascolarctobacterium genera in the constipated rats, whereas Akkermansia, Clostridium_XIVa, Bacteroides, Staphylococcus, and Clostridium_IV were decreased. The combination of defatted hempseed meal and probiotics was found to be effective in relieving constipation, probably due to the enriched amino acids and peptides, such as Thr-Leu and lysinoalanine through correlation analysis. CONCLUSION: Our findings indicated that defatted hempseed meal in yogurt altered the metabolic profile and effectively alleviated constipation in rats, which is a promising therapeutic candidate for constipation. © 2023 Society of Chemical Industry.

Transcriptome sequencing identifies prognostic genes involved in gastric adenocarcinoma.

Gastric adenocarcinoma (GAC) is one of the world's most lethal malignant tumors. It has been established that the occurrence and progression of GAC are linked to molecular changes. However, the pathogenesis mechanism of GAC remains unclear. In this study, we sequenced 6 pairs of GAC tumor tissues and adjacent normal tissues and collected GAC gene expression profile data from the TCGA database. Analysis of this data revealed 465 differentially expressed genes (DEGs), of which 246 were upregulated and 219 were downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that DEGs were observably enriched in ECM-receptor interaction, protein digestion and absorption, and gastric acid secretion pathways. Six key genes (MATN3, COL1A1, COL5A2, P4HA3, SERPINE1 and VCAN) associated with poor GAC prognosis were screened from the protein‒protein interaction (PPI) network by survival analysis, and P4HA3 and MATN3 have rarely been reported to be associated with GAC. We further analyzed the function of P4HA3 in the GAC cell line SGC-7901 by RT‒qPCR, MTT, flow cytometry, colony formation, wound healing, Transwell and western blot assays. We found that P4HA3 was upregulated in the SGC-7901 cell line versus normal control cells. The outcomes of the loss-of-function assay illustrated that P4HA3 significantly enhanced the ability of GAC cells to proliferate and migrate. This study provides a new basis for the selection of prognostic markers and therapeutic targets for GAC.

Boosting the Reversible, High-Rate Na+ Storage Capability of the Hard Carbon Anode Via the Synergistic Structural Tailoring and Controlled Presodiation.

Hard carbons (HCs) are extensively investigated as the potential anodes for commercialization of sodium-ion batteries (SIBs). However, the practical deployment of HC anode suffers from the retarded Na+ diffusion at the high-rate or low-temperature operation scenarios. Herein, a multiscale modification strategy by tuning HC microstructure on the particle level as well as replenishing extra Na+ reservoir for the electrode through a homogeneous presodiation therapy is presented. Consequently, the coulombic efficiency of HC anode can be precisely controlled till the close-to-unit value. Detailed kinetics analysis observes that the Na+ diffusivity can be drastically enhanced by two orders of magnitude at the low potential region (< 0.1 V vs. Na+ /Na), which accelerates the rate-limiting step. As pairing the presodiated HC anode (≈5.0 ± 0.2 mg cm-2 ) with the NaVPO4 F cathode (≈10.3 mg cm-2 ) in the 200 mAh pouch cell, the optimal balance of the cyclability (83% over 1000 cycles), low-temperature behavior till -40 °C as well as the maximized power output of 1500 W kg-1 can be simultaneously achieved. This synergistic modification strategy opens a new avenue to exploit the reversible, ultrafast Na+ storage kinetics of HC anodes, which thus constitutes a quantum leap forward toward high-rate SIB prototyping.

Metagenomics analysis of antibiotic resistance genes, the bacterial community and virulence factor genes of fouled filters and effluents from household water purifiers in drinking water.

The aim of this study was to explore the influence and removal of household water purifiers (HWPs) on emerging contaminants in drinking water, and their distribution characteristics. The antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), virulence factor genes (VFGs) and bacterial communities were profiled in the fouled filters, influents, and effluents from HWPs with five steps of filtration after 150 days operation, using metagenomics. The results showed that the diversity of dominant species in Poly Propylene 1 µm (PP1) and nanofiltration membrane (NM) was significantly higher than that in other filters. Post-activated carbon (AC) was used to detect low species richness or diversity, and the highest proportion of dominant species, which contributes to the greater microbial risk of HWPs effluents in drinking water. The number of dominant bacterial genera in the filters disinfected with chloramine was higher than that in the same group disinfected with chlorine. The bacterial species richness or diversity in water was reduced by the purification of HWPs because the filter elements effectively trapped a variety of microorganisms. The relative abundance of Antibiotic efflux in the effluents of chlorinated and chloraminated HWPs was 5.58 × 10-3 and 4.60 × 10-3, respectively, which was the main resistance mechanism. High abundance of VFGs was found in HWPs effluents and the relative abundance of aggressive VFGs was significantly higher than those of defensive VFGs. Based on the co-occurrence results, 243 subtypes of ARGs co-occurred with VFGs, and a variety of bacteria were thought to be possible ARGs hosts, which indicated that the host bacteria of VFGs in HWP effluents had a stronger attack ability. The effluent of HWPs with only filtration processes is exposed to the risk of ARGs and VFGs. This study helps to understand the actual purification effect of HWPs and provides a theoretical reference for the management and control of ARGs pollution in domestic drinking water.

Mechanisms underlying the toxicity of microplastics to mammals: a review / 预防医学

@#As a new type of environmental pollutants, microplastics are widely distributed in the global ecosystem, and ingestion of microplastics may produce a number of toxic effects. Based on currently available publications, this paper describes the main pathways of exposure to microplastics, and summarizes the toxic mechanisms of microplastics in mammals, including oxidative stress, inflammatory response, immune damage, imbalance of gut microbiota, energy metabolism disorder and DNA damage, so as to provide insights into elucidation of the toxic mechanism mechanisms and health risk assessment of microplastics.

Occurrence and Health Risks of Heavy Metals in Drinking Water of Self-Supplied Wells in Northern China.

Self-supplied wells, an important water resource in remote and scattered regions, are commonly deteriorated by environmental pollution and human activity. In this study, 156 self-supplied well-water samples were collected from remote and scattered areas of Inner Mongolia (NMG), Heilongjiang (HLJ), and the suburbs of Beijing (BJ) in Northern China. Twenty-four heavy metals were identified by using the inductively coupled plasma-mass spectrometry (ICP-MS) and inductively coupled plasma-optical emission spectrometry (ICP-OES), and the associated human health risks were assessed by using standards of the US Environmental Protection Agency (US EPA). The concentrations of four heavy metals (As, Fe, Mn, and Tl) in HLJ, one heavy metal (Tl) in BJ, and ten heavy metals (Al, As, B, Cr, Fe, Mn, Mo, Se, Tl, and Zn) in NMG exceeded the limits set by China or the World Health Organization (WHO). The total carcinogenic risk (TCR) and total non-carcinogenic risk (THQ) exceeding set limits mainly occurred in NMG, compared to HLJ and BJ. Moreover, As accounted for 97.87% and 60.06% of the TCR in HLJ and BJ, respectively, while Cr accounted for 70.83% of the TCR in NMG. The TCR caused by Cd in all three areas had a negligible hazard (<10-4). As accounted for 51.11%, 32.96%, and 40.88% of the THQ in HLJ, BJ, and NMG, respectively. According to the results of the principal component analysis, heavy metals in well water from HLJ and NMG mainly originated from mixed natural processes and anthropogenic sources, whereas, in BJ, most heavy metals probably originated from natural sources. In the future, long-term monitoring of heavy metals in water from self-supplied wells should be conducted for an extensive range of well-water sites, and well water with high As contamination should be monitored more and fully assessed before being used as a drinking-water source.

COVID-19 and mental health disorders in children and adolescents (Review).

The new coronavirus has been present for two years and has had a widespread and sustained impact worldwide. There is growing evidence in the literature that COVID-19 may have negative effects on mental illness in patients and in healthy populations. The unprecedented changes brought about by COVID-19, such as social isolation, school closures, and family stress, negatively affect people's mental health, especially that of children and adolescents. The purpose of this paper is to review the literature and summarize the impact of COVID-19 disorders on children's and adolescents' mental health, the mechanisms and risk factors, screening tools, and intervention and prevention. We hope that the mental dysfunction caused by the pandemic will be mitigated through appropriate and timely prevention and intervention.

Hemp (Cannabis sativa subsp. sativa) Chemical Composition and the Application of Hempseeds in Food Formulations.

Owing to its nutritional and medicinal value, hemp has been cultivated to provide since ancient times. This review aims to map the scientific literature concerning the main functional components and the chemical composition of hemp plant. It is generally acknowledged that each organ of the hemp plant embodies a valuable source, and among them the most pivotal part is the edible fruits hempseeds. Hempseeds are rich in easily digestible proteins, fats, polyunsaturated fatty acids, and insoluble fiber, which are of high nutritional value. Furthermore, the beneficial effects have increased researchers' interests in hempseeds-containing foods. Developed as an indispensable ingredient, hempseed is also a significant supplement in various products, such as bakery food, drinks, snacks and culinary products. Overall, this review intends to promote the further in-depth investigation of approved hemp plants and expand the range of hempseeds adoption in the functional foods field.

A Modular Approach for Diversity-Oriented Synthesis of 1,3-trans-Disubstituted Tetrahydroisoquinolines: Seven-Step Asymmetric Synthesis of Michellamines†B and C.

1,3-trans-Disubstituted tetrahydroisoquinoline (THIQ) is a common heterocyclic structural unit of naphthylisoquinoline alkaloids. The assembly of this structural unit is not trivial, which constitutes a substantial challenge in the total synthesis of naphthylisoquinoline alkaloids and related pharmaceuticals. Herein, we report a modular and convergent method for the rapid assembly of 1,3-trans-disubstituted THIQ frameworks through a three-component Catellani reaction and a AuI -catalyzed cyclization/reduction cascade. With widely available simple aryl iodides, aziridines and (triisopropylsilyl)acetylene as the building blocks, this method paves a practical way for the diversity-oriented synthesis of 1,3-trans-disubstituted THIQs. Based on this new method, concise syntheses of an analogue of the new drug mevidalen and four naphthylisoquinoline alkaloids have been accomplished, demonstrating the broad synthetic utility of this approach.

Reconsidering treatment guidelines for acute myocardial infarction during the COVID-19 pandemic.

BACKGROUND: COVID-19 affects healthcare resource allocation, which could lead to treatment delay and poor outcomes in patients with acute myocardial infarction (AMI). We assessed the impact of the COVID-19 pandemic on AMI outcomes. METHODS: We compared outcomes of patients admitted for acute ST-elevation MI (STEMI) and non-STEMI (NSTEMI) during a non-COVID-19 pandemic period (January-February 2019; Group 1, n = 254) and a COVID-19 pandemic period (January-February 2020; Group 2, n = 124). RESULTS: For STEMI patients, the median of first medical contact (FMC) time, door-to-balloon time, and total myocardial ischemia time were significantly longer in Group 2 patients (all p < 0.05). Primary percutaneous intervention was performed significantly more often in Group 1 patients than in Group 2 patients, whereas thrombolytic therapy was used significantly more often in Group 2 patients than in Group 1 patients (all p < 0.05). However, the rates of and all-cause 30-day mortality and major adverse cardiac event (MACE) were not significantly different in the two periods (all p > 0.05). For NSTEMI patients, Group 2 patients had a higher rate of conservative therapy, a lower rate of reperfusion therapy, and longer FMC times (all p < 0.05). All-cause 30-day mortality and MACE were only higher in NSTEMI patients during the COVID-19 pandemic period (p < 0.001). CONCLUSIONS: COVID-19 pandemic causes treatment delay in AMI patients and potentially leads to poor clinical outcome in NSTEMI patients. Thrombolytic therapy should be initiated without delay for STEMI when coronary intervention is not readily available; for NSTEMI patients, outcomes of invasive reperfusion were better than medical treatment.

Association between serum low-density neutrophils and acute-onset and recurrent Guillain-Barré syndrome.

BACKGROUND AND AIM: Guillain-Barré syndrome (GBS) is one of the most common causes of acute flaccid paralysis. A timely assessment of this disease condition and its treatments are of vital importance to patients diagnosed with GBS. The purpose of this study is to investigate the variation trend of neutrophils along with disease courses and assess the prognostic value of serum low-density neutrophils (LDNs) in the acute-onset and recurrence of GBS. METHODS: A total of 176 GBS patients were recruited. Patients were evaluated with Medical Research Council (MRC) sum score and the Hughes Functional Grading Scale score upon admission. Peripheral blood samples were collected for routine testing. Flow cytometry analysis was performed to identify LDNs. All patients were followed up to collect disease condition data. RESULTS: The total neutrophil ratios and counts were significantly higher in patients with acute-onset GBS compared to healthy controls (HCs). These counts/ratios decreased during remission and re-elevated in recurrent GBS patients. However, no correlation was observed between the total neutrophil counts/ratios and the MRC sum score. The LDNs collected from different GBS courses were identified using flow cytometry. The counts and ratios were significantly higher in acute-onset GBS and recurrent GBS compared to HCs and patients in remission. The LDN counts/ratios displayed a negative correlation with the MRC sum scores in acute-onset GBS and recurrent GBS. CONCLUSION: Our findings suggest that LDN counts/ratios are positively correlated with the acute-onset and recurrence of GBS and its severity. Therefore, LDNs might serve as an accessible prognostic indicator for disease progression monitoring.