Delivery Hospitalization Cardiac and Respiratory Complications during SARS-CoV-2 Delta Variant Dominance.

In 2021, the SARS-CoV-2 Delta variant rapidly proliferated and became dominant. Some but not all research evidence supports that Delta was associated with increased maternal risk. The purpose of this study was to determine whether Delta was associated with risk for cardiac and respiratory complications in a national sample. Of an estimated 3,495,188 delivery hospitalizations in 2021, 1.8% of pre-Delta deliveries (n=29,580) (January-June) and 2.1% of Delta-period deliveries (n=37,545) (July-December) had a COVID-19 diagnosis. The Delta period was associated with increased adjusted odds of respiratory complications (aOR 1.54, 95% CI 1.41, 1.69) and cardiac SMM (aOR 1.54, 95% CI 1.40, 1.69). Among deliveries with a COVID diagnosis, the Delta period was associated with higher incidence of respiratory complications (8.4% versus 3.7%) and cardiac SMM (8.4% versus 3.5%) (p<0.01 for both). These findings corroborate prior clinical studies suggesting that the Delta strain was associated with an increased maternal population-level clinical burden.

Temporal and spatial evolution simulation and attribution analysis of vegetation photosynthesis over the past 21 years based on satellite SIF data: a case study from Asia.

Photosynthesis in vegetation is one of the key processes in maintaining regional ecological balance and climate stability, and it is of significant importance for understanding the health of regional ecosystems and addressing climate change. Based on 2001-2021 Global OCO-2 Solar-Induced Fluorescence (GOSIF) dataset, this study analyzed spatiotemporal variations in Asian vegetation photosynthesis and its response to climate and human activities. Results show the following: (1) From 2001 to 2021, the overall photosynthetic activity of vegetation in the Asian region has shown an upward trend, exhibiting a stable distribution pattern with higher values in the eastern and southern regions and lower values in the central, western, and northern regions. In specific regions such as the Turgen Plateau in northwestern Kazakhstan, Cambodia, Laos, and northeastern Syria, photosynthesis significantly declined. (2) Meteorological factors influencing photosynthesis exhibit differences based on latitude and vertical zones. In low-latitude regions, temperature is the primary driver, while in mid-latitude areas, solar radiation and precipitation are crucial. High-latitude regions are primarily influenced by temperature, and high-altitude areas depend on precipitation and solar radiation. (3) Human activities (56.44%) have a slightly greater impact on the dynamics of Asian vegetation photosynthesis compared to climate change (43.56%). This research deepens our comprehension of the mechanisms behind the fluctuations in Asian vegetation photosynthesis, offering valuable perspectives for initiatives in environmental conservation, sustainability, and climate research.

Efficacy and Safety of Polycaprolactone in Treating Nasolabial Folds: A Prospective, Multicenter, and Randomized Controlled Trial.

Nasolabial folds (NLFs) are the most pronounced sign of facial aging. This study explored the efficacy and safety of polycaprolactone gel in treating Chinese patients with moderate-to-severe NLFs. Patients with moderate-to-severe NLF who wished to be treated by dermal fillers were recruited from three centers between July 2017 and September 2019. The randomizing ratio was 1:1 in the polycaprolactone group (polycaprolactone injection) or control group (sodium hyaluronate gel injection). The primary endpoint was the effectiveness rate of Wrinkle Severity Rating Score (WSRS) scores at 12 months after injection. The full-analysis set (FAS) and safety sets had 80 patients in the polycaprolactone group and control group, respectively. In the FAS, the effectiveness rate at 12 months in the polycaprolactone group was 88.8% compared with 23.8% in controls (P < 0.001). The improvement in WSRS sustained during 12 months in the polycaprolactone group, while gradually vanished in the control group since 3 months after surgery. The global aesthetic improvement scale (GAIS) by investigator assessments was improved, much improved, or very much improved in all patients during follow-up, while the proportion of patients with a "no change" assessment gradually increased during follow-up after 6 months in the control group. The rates of injection-related adverse event (AE) and serve injection-related AE were 8.8 versus 11.3% and 0 versus 1.3% in the polycaprolactone group and control groups, respectively. Polycaprolactone gel injection is effective and safe to treat moderate-to-severe NLFs in Chinese patients.

[Clinical effect of different immunosuppressive treatment regimens in children with ocular myasthenia gravis: a retrospective analysis]. / å„¿ç«¥çœ¼è‚Œåž‹é‡ç—‡è‚Œæ— åŠ›ä¸åŒå ç–«æŠ‘åˆ¶å‰‚æ²»ç–—æ–¹æ¡ˆçš„å›žé¡¾æ€§åˆ†æž.

OBJECTIVES: To investigate the clinical effect of different immunosuppressive treatment regimens in children with ocular myasthenia gravis (OMG). METHODS: A retrospective analysis was conducted on 130 children with OMG who were treated in the Department of Neurology, Jiangxi Children's Hospital, from February 2018 to February 2023. According to the treatment regimen, they were divided into four groups: glucocorticoid (GC) group (n=29), mycophenolate mofetil (MMF) group (GC+MMF; n=33), methotrexate (MTX) group (GC+MTX; n=30), and tacrolimus (FK506) group (GC+FK506; n=38). Treatment outcomes and adverse reactions were compared among the groups. RESULTS: After 3 months of treatment, the FK506 group had significantly lower scores of Myasthenia Gravis Quantitative Scale and Myasthenia Gravis-Specific Activities of Daily Living than the other three groups (P<0.05). After 3 months of treatment, the FK506 group had a significantly lower dose of prednisone than the GC group, and after 6 and 9 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower dose of prednisone than the GC group (P<0.05). After 12 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower incidence rate of GC-related adverse reactions than the GC group (P<0.05). CONCLUSIONS: For children with OMG, the addition of various immunosuppressants can reduce the dosage of GC and adverse reactions. Among them, FK506 shows superior efficacy compared to other immunosuppressants in the early treatment of OMG.

A case report of atypical hemiplegic migraine with nonheadache onset in a Chinese child.

BACKGROUND: Hemiplegic migraine (HM) is an uncommon subtype of migraine with aura including motor weakness. The core symptoms of HM are headache and motor weakness. However, we report a rare case of atypical HM with nonheadache onset in a Chinese child who was misdiagnosed several times. CASE PRESENTATION: We report a Chinese boy whose onset was sudden when he was 3 years old. He presented with a variety of phenotypes, including fever, vomiting, alternating hemiplegia, and drowsiness, but no headache in the initial stages. Magnetic resonance imaging (MRI) demonstrated unilateral cerebral oedema during the initial episode of hemiplegia. These symptoms recurred many times. As the disease progressed, the patient developed episodic headache. The patient was misdiagnosed several times with encephalitis, alternating hemiplegia of childhood (AHC) and mitochondrial encephalopathy. Whole-exome next-generation sequencing revealed a de novo heterozygous missense mutation in the ATP1A2 gene(p.Gly715Arg) classified as pathogenic and eventually led to a diagnosis of HM when he was 11 years old. Flunarizine was subsequently administered, and no recurrence was found during follow-up. CONCLUSIONS: HM in children may be atypical in the initial stage of the disease, which could manifest as fever, alternating hemiplegia and drowsiness but no headache at the onset. This could easily lead to misdiagnosis. With age, it may eventually manifest as typical HM. Therefore, attention should be given to differentiation in clinical practice.When similar clinical cases appear, gene detection is particularly important, which is conducive to early diagnosis and treatment.

Down-regulated miR-15a mediates the epithelial-mesenchymal transition in renal tubular epithelial cells promoted by high glucose.

High glucose (HG) has been reported to be associated with renal dysfunction. And one potential mechanism underlining the dysfunction is the epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells. Present study showed that EMT was induced in the HG-treated renal tubular epithelial cells by promoting the expression of mesenchymal phenotype molecules, such as α-SMA and collagen I, and down-regulating the expression of epithelial phenotype molecule E-cadherin. Moreover, we have identified the down-regulation of miR-15a which was accompanied with the HG-induced EMT. And the miR-15a overexpression inhibited the α-SMA, collagen I expression, and the promotion of E-cadherin expression by targeting and down-regulating AP4 which was also significantly promoted by the HG in the renal tubular epithelial cells. Thus, this study revealed that the weakening regulation on the AP4 expression by miR-15a might contribute to the HG-induced EMT in the renal tubular epithelial cells.

Identification of a novel METTL23 gene variant in a patient with an intellectual development disorder: a literature review and case report.

METTL23 belongs to a family of protein lysine methyltransferases that methylate non-histone proteins. Recently, the METTL23 gene has been reported to be related to an intellectual developmental disorder, autosomal recessive 44. Patients present with developmental delay, intellectual disability (ID), and variable dysmorphic features. Here, we report on a Chinese girl who presented with global developmental delay, abnormal brain structure, and multiple facial deformities, including a short/upturned nose with a sunken bridge, thin lips, and flat occiput. Whole-exome sequencing identified a novel variant (NM_001080510.5: c.322+1del) on the METTL23 gene. This variant was not collected on public human variants databases such as gnomAD, predicted to influence the splicing as a classical splicing variant, and classified as Pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Since patients with METTL23-related ID are rare, we summarize and compare the clinical phenotype of reported patients with METTL23 variants. Our report further expands the METTL23 variants and provides new evidence for clinical diagnosis of METTL23-related ID.

Disparities in pathways to reduction mammaplasty: A single institution review of 425 women with macromastia.

BACKGROUND: Reduction mammaplasty improves the quality of life by providing functional and aesthetic benefits to women with macromastia. This study contributes to the existing literature on socioeconomic and clinical barriers to referral for plastic surgery procedures by focusing specifically on reduction mammaplasty. METHODS: Patients with macromastia were identified via a chart review in a single institution from 2021-2022. The treatment pathway for each patient was characterized by reception of referral, completion of plastic surgery consultation, and eventual reception of surgery. After controlling for clinical covariates, multivariate logistic regression was applied to quantify the independent impact of race, insurance, and language status on the completion of surgery (p < 0.05). RESULTS: The final patient cohort included 425 women with macromastia. Among the 151 patients who were first seen by a primary care physician, 64 (42%) completed an initial plastic surgery consultation. Among all patients, 160 (38%) eventually underwent reduction mammaplasty. Multivariate regression predictions indicated a lower likelihood of completing breast reduction surgery in patients with current smoking history (OR: 0.08, 95% CI: 0.01-0.59) and higher body mass index (BMI) (OR: 0.94, 95% CI: 0.90-0.97) (p < 0.05). Minority race and ethnicity, private insurance status, and primary language status were not significant predictors of this outcome (p > 0.05). CONCLUSIONS: In this study, the socioeconomic variables were not independent predictors of breast reduction surgery completion. However, the association of minority race and ethnicity and nonprivate insurance status with the most common reasons for breast reduction deferral suggest an indirect influence of socioeconomic status on the treatment pathway.

Enhancing SSVEP-BCI Performance Under Fatigue State Using Dynamic Stopping Strategy.

Steady-state visual evoked potential (SSVEP)-based brain-computer interfaces (BCIs) have emerged as a prominent technology due to their high information transfer rate, rapid calibration time, and robust signal-to-noise ratio. However, a critical challenge for practical applications is performance degradation caused by user fatigue during prolonged use. This work proposes novel methods to address this challenge by dynamically adjusting data acquisition length and updating detection models based on a fatigue-aware stopping strategy. Two 16-target SSVEP-BCIs were employed, one using low-frequency and the other using high-frequency stimulation. A self-recorded fatigue dataset from 24 subjects was utilized for extensive evaluation. A simulated online experiment demonstrated that the proposed methods outperform the conventional fixed stopping strategy in terms of classification accuracy, information transfer rate, and selection time, irrespective of stimulation frequency. These findings suggest that the proposed approach can significantly improve SSVEP-BCI performance under fatigue conditions, leading to superior performance during extended use.

Structural characterization and calcium absorption-promoting effect of sucrose-calcium chelate in Caco-2 monolayer cells and mice.

Sucrose emerges as a chelating agent to form a stable sucrose-metal-ion chelate that can potentially improve metal-ion absorption. This study aimed to analyze the structure of sucrose-calcium chelate and its potential to promote calcium absorption in both Caco-2 monolayer cells and mice. The characterization results showed that calcium ions mainly chelated with hydroxyl groups in sucrose to produce sucrose-calcium chelate, altering the crystal structure of sucrose (forming polymer particles) and improving its thermal stability. Sucrose-calcium chelate dose dependently increased the amount of calcium uptake, retention, and transport in the Caco-2 monolayer cell model. Compared to CaCl2 , there was a significant improvement in the proportion of absorbed calcium utilized for transport but not retention (93.13 ± 1.75% vs. 67.67 ± 7.55%). Further treatment of calcium channel inhibitors demonstrated the active transport of sucrose-calcium chelate through Cav1.3. Cellular thermal shift assay and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays indicated that the ability of sucrose-calcium chelate to promote calcium transport was attributed to its superior ability to bind with PMCA1b, a calcium transporter located on the basement membrane, and stimulate its gene expression compared to CaCl2 . Pharmacokinetic analysis of mice confirmed the calcium absorption-promoting effect of sucrose-calcium chelate, as evident by the higher serum calcium level (44.12 ± 1.90 mg/L vs. 37.42 ± 1.88 mmol/L) and intestinal PMCA1b gene expression than CaCl2 . These findings offer a new understanding of how sucrose-calcium chelate enhances intestinal calcium absorption and could be used as an ingredient in functional foods to treat calcium deficiency. PRACTICAL APPLICATION: The development of high-quality calcium supplements is crucial for addressing the various adverse symptoms associated with calcium deficiency. This study aimed to prepare a sucrose-calcium chelate and analyze its structure, as well as its potential to enhance calcium absorption in Caco-2 monolayer cells and mice. The results demonstrated that the sucrose-calcium chelate effectively promoted calcium absorption. Notably, its ability to enhance calcium transport was linked to its strong binding with PMCA1b, a calcium transporter located on the basement membrane, and its capacity to stimulate PMCA1b gene expression. These findings contribute to a deeper understanding of how the sucrose-calcium chelate enhances intestinal calcium absorption and suggest its potential use as an ingredient in functional foods for treating calcium deficiency.

IDH2-NADPH pathway protects against acute pancreatitis via suppressing acinar cell ferroptosis.

BACKGROUND AND PURPOSE: Acute pancreatitis (AP) is associated with acinar cell death and inflammatory responses. Ferroptosis is characterized by an overwhelming lipid peroxidation downstream of metabolic dysfunction, in which NADPH-related redox systems have been recognized as the mainstay in ferroptosis control. Nevertheless, it remains unknown how ferroptosis is regulated in AP and whether we can target it to restrict AP development. EXPERIMENTAL APPROACH: Metabolomics were applied to explore changes in metabolic pathways in pancreatic acinar cells (PACs) in AP. Using wild-type and Ptf1aCreERT2/+IDH2fl/fl mice, AP was induced by caerulein and sodium taurocholate (NaT). IDH2 overexpressing adenovirus was constructed for infection of PACs. Mice or PACs were pretreated with inhibitors of FSP1 or glutathione reductase. Pancreatitis severity, acinar cell injury, mitochondrial morphological changes and pancreatic lipid peroxidation were analysed. KEY RESULTS: Unsaturated fatty acid biosynthesis and the tricarboxylic acid cycle pathways were significantly altered in PACs during AP. Inhibition of ferroptosis reduced mitochondrial damage, lipid peroxidation and the severity of AP. During AP, the NADPH abundance and IDH2 expression were decreased. Acinar cell-specific deletion of IDH2 exacerbated acinar cell ferroptosis and pancreatic injury. Pharmacological inhibition of NADPH-dependent GSH/GPX4 and FSP1/CoQ10 pathways abolished the protective effect of IDH2 overexpression on ferroptosis in acinar cells. CoQ10 supplementation attenuated experimental pancreatitis via inhibiting acinar cell ferroptosis. CONCLUSION AND IMPLICATIONS: We identified the IDH2-NADPH pathway as a novel regulator in protecting against AP via restricting acinar cell ferroptosis. Targeting the pathway and its downstream may shed light on AP treatment.

The Role of Nicotine Metabolic Rate on Nicotine Dependence and Rewarding: Nicotine Metabolism in Chinese Male Smokers and Male Mice.

The exact relationship between nicotine metabolism and dependence is not fully understood but is known to be influenced at a molecular level by genetic factors. A sample comprising 274 Chinese adult male smokers was categorized into groups based on their metabolic rates, namely fast, intermediate, and slow metabolizers. We then measured their smoking topography, evaluated their nicotine dependence, and assessed the rewarding effects. Based on these findings, we proposed the hypothesis that the rate of nicotine metabolism could influence the level of dopamine release which in turn had repercussions on the pleasurable and rewarding effects. To test this hypothesis, male mice were selected with different nicotine metabolic rates that closely resembled in the smoker group. We evaluated their nicotine dependence and rewarding effects through conditioned place preference and withdrawal symptom tests, supplemented with dopamine release measurements. In both animal and human, the slow metabolism group (SMG) required less nicotine to maintain a comparable level of dependence than the fast metabolism group (FMG). The SMG could achieve similar rewarding effects to FMG despite consuming less nicotine. Comparable dopamine levels released were therefore critical in setting the nicotine acquisition behavior in this animal model and also for the smokers tested. Our findings suggested that even within the same ethnicity of established smokers (Chinese Han), differences in nicotine metabolism were an important parameter to modulate the degree of nicotine dependence.

Identification of a human type XVII collagen fragment with high capacity for maintaining skin health.

Collagen XVII (COL17) is a transmembrane protein that mediates skin homeostasis. Due to expression of full length collagen was hard to achieve in microorganisms, arising the needs for selection of collagen fragments with desired functions for microbial biosynthesis. Here, COL17 fragments (27-33 amino acids) were extracted and replicated 16 times for recombinant expression in Escherichia coli. Five variants were soluble expressed, with the highest yield of 223 mg/L. The fusion tag was removed for biochemical and biophysical characterization. Circular dichroism results suggested one variant (sample-1707) with a triple-helix structure at >37 °C. Sample-1707 can assemble into nanofiber (width, 5.6 nm) and form hydrogel at 3 mg/mL. Sample-1707 was shown to induce blood clotting and promote osteoblast differentiation. Furthermore, sample-1707 exhibited high capacity to induce mouse hair follicle stem cells differentiation and osteoblast migration, demonstrating a high capacity to induce skin cell regeneration and promote wound healing. A strong hydrogel was prepared from a chitosan and sample-1707 complex with a swelling rate of >30 % higher than simply using chitosan. Fed-batch fermentation of sample-1707 with a 5-L bioreactor obtained a yield of 600 mg/L. These results support the large-scale production of sample-1707 as a biomaterial for use in the skin care industry.

Calpain Inhibitor Calpeptin Improves Pancreatic Fibrosis in Mice with Chronic Pancreatitis by Inhibiting the Activation of Pancreatic Stellate Cells.

BACKGROUND: Pancreatic fibrosis is a hallmark feature of chronic pancreatitis (CP), resulting in persistent damage to the pancreas. The sustained activation of pancreatic stellate cells (PSCs) plays a pivotal role in the progression of pancreatic fibrosis and is a major source of extracellular matrix (ECM) deposition during pancreatic injury. METHODS: Calpain is a calcium-independent lysosomal neutral cysteine endopeptidase and was found to be correlated to various fibrotic diseases. Studies have revealed that calpeptin, a calpain inhibitor, can improve the fibrosis process of multiple organs. This study investigated the effect of the calpain inhibitor, calpeptin, on fibrosis in experimental CP and activation of cultured PSCs in mice. CP was induced in mice by repeated injections of cerulein for four weeks in vivo, and the activation process of mouse PSCs was isolated and cultured in vitro. Then, the inhibitory effect of calpeptin on pancreatic fibrosis was confirmed based on the histological damage of CP, the expression of α-smooth muscle actin (α-SMA) and collagen-Iα1(Col1α1), and the decrease in mRNA levels of calpain-1 and calpain-2. RESULTS: In addition, it was revealed that calpeptin can inhibit the activation process of PSCs and induce significant PSCs apoptosis by downregulating the expression of calpain-1, calpain-2 and TGF-ß1, and the expression and phosphorylation of smad3 in vitro. CONCLUSION: These results suggest that the calpain inhibitor, calpeptin, plays a key role in the regulation of PSC activation by inhibiting the TGF-ß1/smad3 signaling pathway, which supports the potential of calpeptin as an inhibitor of pancreatic fibrosis in mice by interfering with calpain.

[Mapping environmental vulnerability from ETM + data in the Yellow River Mouth Area].

The environmental vulnerability retrieval is important to support continuing data. The spatial distribution of regional environmental vulnerability was got through remote sensing retrieval. In view of soil and vegetation, the environmental vulnerability evaluation index system was built, and the environmental vulnerability of sampling points was calculated by the AHP-fuzzy method, then the correlation between the sampling points environmental vulnerability and ETM + spectral reflectance ratio including some kinds of conversion data was analyzed to determine the sensitive spectral parameters. Based on that, models of correlation analysis, traditional regression, BP neural network and support vector regression were taken to explain the quantitative relationship between the spectral reflectance and the environmental vulnerability. With this model, the environmental vulnerability distribution was retrieved in the Yellow River Mouth Area. The results showed that the correlation between the environmental vulnerability and the spring NDVI, the September NDVI and the spring brightness was better than others, so they were selected as the sensitive spectral parameters. The model precision result showed that in addition to the support vector model, the other model reached the significant level. While all the multi-variable regression was better than all one-variable regression, and the model accuracy of BP neural network was the best. This study will serve as a reliable theoretical reference for the large spatial scale environmental vulnerability estimation based on remote sensing data.

[Biomanufacturing of bioactive compounds: current situation, challenges, and future perspectives].

Biomanufacturing uses biological systems, including cells, microorganisms, and enzymes, to produce natural or synthetic molecules with biological activities for use in various industries, such as pharmaceuticals, cosmetics, and agriculture. These bioactive compounds are expected to play important roles in improving the quality of life and prolonging its length. Fortunately, recent advances in synthetic biology and automation technologies have accelerated the development of biomanufacturing, enabling us to create new products and replace conventional methods in a more sustainable manner. As of now, the role of biomanufacturing in the growth and innovation of bioeconomy is steadily increasing, and this techbology becomes a prevalent technology in global markets. To gain a comprehensive understanding of this field, this article presents a retrospective review of Bloomage Biotechnology's Research and Development and briefly reviews the developments of biomanufacturing and offers insights into the futre prospects. In conclusion, biomanufacturing will continue to be an important, environmentally friendly, and sustainable production mode in the ongoing development of bioeconomy.

Difference in the recruitment of intrinsic foot muscles in the elderly under static and dynamic postural conditions.

Background: The effect of foot, especially intrinsic muscles, on postural control and its related mechanisms remain unclear due to the complex structure. Therefore, this study aims to investigate the activation of intrinsic foot muscles in the elderly under static and dynamic postural tasks. Methods: Twenty-one elderly participants were included to perform different postural tests (sensory organization test (SOT), motor control test (MCT), limit of stability test (LOS), and unilateral stance test) by a NeuroCom Balance Manager System. The participants were instructed to maintain postural stability under conditions with combined different sensory inputs (vision, vestibular, and proprioception) in SOT as well as conditions with translation disturbance in MCT, and to perform an active weight-shifting tasks in LOS. During these tasks, muscle activation were simultaneously acquired from intrinsic foot muscles (abductor halluces (AbH) and flexor digitorum brevis (FDB)) and ankle muscles (anterior tibialis, medial head of gastrocnemius, lateral head of gastrocnemius, and peroneus longus). The root-mean-square amplitude of these muscles in postural tasks was calculated and normalized with the EMG activity in unilateral stance task. Results: The activation of intrinsic foot muscles significantly differed among different SOT tasks (p < 0.001). Post-hoc tests showed that compared with that under normal condition 1 without sensory interference, EMGs increased significantly under sensory disturbance (conditions 2-6). By contrast, compared with that under the single-sensory disturbed conditions (conditions 2-4; 2 for disturbed vision, 3 for disturbed vestibular sensation, 4 for disturbed proprioception), activation was significantly greater under the dual-sensory disturbed postural tasks (conditions 5 and 6; 5 for disturbed vision and proprioception, 6 for disturbed vestibular sensation and proprioception). In MCT, EMGs of foot muscles increased significantly under different translation speeds (p < 0.001). In LOS, moderate and significant correlations were found between muscle activations and postural stability parameters (AbH, r = 0. 355-0.636, p < 0.05; FDB, r = 0.336-0.622, p < 0.05). Conclusion: Intrinsic foot muscles play a complementary role to regulate postural stability when disturbances occur. In addition, the recruitment magnitude of intrinsic foot muscles is positively correlated with the limit of stability, indicating their contribution to increasing the limits of stability in the elderly.

De novo variants in PHF21A cause intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures: A case report and literature review.

PURPOSE: PHF21A has been associated with intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures (IDDBCS). Here, we report a new patient with IDDBCS and review previously reported patients. METHODS: We reviewed the phenotypic and genetic spectrum of the newly diagnosed patient and previously reported patients with IDDBCS. RESULTS: Among 12 patients (11 whose cases were previously reported and the patient whose case we report here), all patients (100%) had intellectual disability (ID) and motor development delay. Three of 8 patients (37.5%) for whom information on cognition was available had severe ID; ID was moderate in two patients (25%) and mild in three patients (37.5%). Seven of the 12 patients (58.33%) had an epileptic phenotype, and the majority (5/7, 71.42%) of affected individuals developed developmental and epileptic encephalopathy (DEE). Of the 5 patients with DEE, three developed infantile epileptic spasm syndrome (IESS). The seizures of 2 patients (2/5, 40%) were controlled by antiseizure medications. Overgrowth, ADHD, hypotonia, ASD, and sleep disorders were observed in 100%, 77.78%, 70%, 50%, and 33.33% of patients, respectively. All of the variants (100%) were de novo heterozygous variants. Three of the 12 patients (25%) had the same variant (p.Arg580*). The most common types of variants were frameshift variants (7/12, 58.33%), followed by nonsense variants (4/12, 33.33%) and missense variants (1/12, 8.33%). Genotype-phenotype relationships for IDDBCS were uncertain, as phenotypic variability was observed among patients with the same variant (p.Arg580*). The patient whose case we report here had a novel PHF21A gene variant (p.Gln97fs*20), which caused neurodevelopmental delay, macrocephaly, and IESS. CONCLUSION: The core phenotypes of IDDBCS include neurodevelopmental delay (intellectual disability and impaired motor skills), craniofacial abnormalities, and overgrowth. ADHD, hypotonia, epilepsy, ASD, and sleep disorders are common symptoms of IDDBCS. Notably, DEE is the dominant phenotype of epilepsy, especially IESS. PHF21A may be a candidate gene for DEE. De novo variants are the main mode of inheritance. The most common types of variants are frameshift variants, and the variant p.Arg580* in PHF21A is located at a mutation hot spot.

Structural Characterization of Zinc-Sucrose Complex and Its Ability to Promote Zinc Absorption in Caco-2 Monolayer Cells and Mice.

Sucrose emerges as a metal-ion chelating agent with excellent stability that may increase metal-ion absorption. This study aimed to characterize the structure of zinc-sucrose complex and investigate its ability to promote zinc absorption in Caco-2 monolayer cells and mice. Based on the results of the inductively coupled plasma emission spectrometer (ICP-ES), scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDX), and Fourier transform infrared spectroscopy (FT-IR), it can be inferred that zinc and sucrose were chelated at a 1:1 ratio, with the hydroxyl groups playing a significant role. The Caco-2 monolayer cell model revealed that zinc-sucrose complex increased the amount of zinc uptake, retention, and transport in a dose- and time-dependent manner. Through the upregulation of genes and proteins for ZIP4, MT1, and DMT1, treatment with zinc-sucrose complex improved the proportion of absorbed zinc utilized for transport compared to ZnCl2 (26.21 ± 4.96 versus 8.50 ± 1.51%). Pharmacokinetic analysis of mice confirmed the zinc absorption-promoting effect of zinc-sucrose complex, as indicated by the considerably higher serum zinc level (4.16 ± 0.53 versus 2.56 ± 0.45 mg/L) and intestinal ZIP4, MT1, and DMT1 gene expression than ZnCl2. Further treatment of different zinc channel inhibitors and CETSA demonstrated the direct interaction of zinc-sucrose complex with ZIP4 protein and ZIP4-mediated cellular transport of zinc-sucrose complex. These findings provide a novel insight into the zinc absorption-promoting mechanism of zinc-sucrose complex, which could be used as an ingredient in functional foods to treat zinc deficiency.

Identification of OLA1 as a Novel Protein Target of Vitexin to Ameliorate Dextran Sulfate Sodium-Induced Colitis with Tissue Thermal Proteome Profiling.

Vitexin, which exists in various medicinal plants and food sources, has recently received increasing attention because of its anti-inflammatory properties. This study aims to identify the protein target of vitexin that ameliorates dextran sulfate sodium (DSS)-induced colitis. The results showed that vitexin not only alleviated the clinical symptoms and colonic damage in mice with DSS-induced colitis but also suppressed the colonic production of inflammatory cytokines (IL-1ß, IL-6, ICAM, and VCAM) and enhanced the expression of barrier-associated proteins (ZO-1, Occludin, and E-cadherin). Based on tissue thermal proteome profiling (Tissue-TPP) and molecular docking, OLA1 was creatively identified as a potential protein target for vitexin. Further siRNA-mediated knockdown of the OLA1 gene in Caco-2 cells demonstrated the ability of OLA1 to increase Nrf2 protein expression and, thus, mediated the anti-inflammatory effects of vitexin. Interaction of the OLA1-vitexin complex with Keap1 protein to disrupt the Keap1-Nrf2 interaction may be required for activating Nrf2. Our findings revealed a novel role for OLA1 as a protein target of vitexin that contributes to its anti-inflammatory action by activating Nrf2, which may provide a promising molecular mechanism for novel therapeutic strategies to treat colitis and the associated systemic inflammation.