The Bifunctional Effects of Lactoferrin (LFcinB11) in Inhibiting Neural Cell Adhesive Molecule (NCAM) Polysialylation and the Release of Neutrophil Extracellular Traps (NETs).

The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM) is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and aggressive clinical status. Thus, it is important to select a proper drug to block tumor cell migration during clinical treatment. In this study, we proposed that lactoferrin (LFcinB11) may be a better candidate for inhibiting NCAM polysialylation when compared with CMP and low-molecular-weight heparin (LMWH), which were determined based on our NMR studies. Furthermore, neutrophil extracellular traps (NETs) represent the most dramatic stage in the cell death process, and the release of NETs is related to the pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis, and vascular disorders. In this study, the molecular mechanisms involved in the inhibition of NET release using LFcinB11 as an inhibitor were also determined. Based on these results, LFcinB11 is proposed as being a bifunctional inhibitor for inhibiting both NCAM polysialylation and the release of NETs.

Application of online to offline teaching mode in the training of non-anesthesiology residents in the department of anesthesiology: a randomized, controlled trial.

Objective: To explore the effect of applying the online to offline teaching mode in the training of non-anesthesiology residents in department of anesthesiology. Trial design: The randomized controlled trial was performed on non-anesthesiology residents from Affiliated Jiangning Hospital of Nanjing Medical University. Methods: All selected residents were randomly divided into the traditional teaching group (Group T) and the online to offline teaching group (Group O) by the random number table method. Traditional teaching mode was used in Group T, while the online to offline teaching mode was used in Group O. The training period lasted for two months. At the end of the training, theoretical and clinical skills were assessed for all residents, and students' satisfaction scores on teaching were investigated from the aspects of teaching mode, stimulating learning interest, improving learning process and teaching satisfaction. The teaching efficiency was compared and analyzed in the two groups. Results: In total, 39 cases in Group O and 38 cases in Group T were included in the statistical analysis. Compared with Group T, theory test scores, clinical skills test scores, and overall scores improved significantly in Group O (82.2 ± 8.1 vs. 91.3 ± 7.6; 85.1 ± 4.7 vs. 93.3 ± 5.4 and 83.4 ± 6.4 vs. 92.1 ± 6.7, respectively, p < 0.01). Compared with Group T, scores on teaching mode, stimulating learning interest, improving learning process and teaching satisfaction were higher in Group O (81.1 ± 6.9 vs. 93.7 ± 5.2; 83.6 ± 5.8 vs. 91.6 ± 6.4; 82.4 ± 5.3 vs. 90.9 ± 4.8 and 82.1 ± 5.9 vs. 92.1 ± 5.5, respectively, p < 0.01). Conclusion: The online to offline teaching mode can improve the level of professional theory and clinical skill operation, and teaching satisfaction of the non-anesthesiology residents in department of anesthesiology, thus improving the teaching effectiveness.

Reversible Switching Between Microwave Absorption and EMI Shielding of VO2 Composite Foam.

Developing lightweight composite with reversible switching between microwave (MW) absorption and electromagnetic interference (EMI) shielding is promising yet remains highly challenging due to the completely inconsistent attenuation mechanism for electromagnetic (EM) radiation. Here, a lightweight vanadium dioxide/expanded polymer microsphere composites foam (VO2/EPM) is designed and fabricated with porous structures and 3D VO2 interconnection, which possesses reversible switching function between MW absorption and EMI shielding under thermal stimulation. The VO2/EPM exhibits MW absorption with a broad effective absorption bandwidth of 3.25 GHz at room temperature (25 °C), while provides EMI shielding of 23.1 dB at moderately high temperature (100 °C). This reversible switching performance relies on the porous structure and tunability of electrical conductivity, complex permittivity, and impedance matching, which are substantially induced by the convertible crystal structure and electronic structure of VO2. Finite element simulation is employed to qualitatively investigate the change in interaction between EM waves and VO2/EPM before and after the phase transition. Moreover, the application of VO2/EPM is demonstrated with a reversible switching function in controlling wireless transmission on/off, showcasing its excellent cycling stability. This kind of smart material with a reversible switching function shows great potential in next-generation electronic devices.

The relationship between health-promoting behaviors and negative emotions in college freshmen: a cross-lagged analysis.

Background: The prevalence of mental health issues has been gradually increasing among college students in recent years. Improvements in mental health can be achieved through changes in daily behavior and the use of psychological counseling. This study aims to investigate the relationship between health-promoting behaviors and negative emotions among college freshmen as they enter the university. It also examines the impact of various sub-dimensions of health-promoting behaviors and other factors on the negative emotions (stress, anxiety, and depression) experienced by college freshmen. Methods: Using the Negative Emotion and Health-Promoting Behavior scales, a 7-month longitudinal study was conducted on 4,252 college freshmen, with collection of data at two time points (T1: November 12, 2021; T2: June 17, 2022). Out of this longitudinal study, 3,632 valid samples were obtained. This research aimed to explore the association and impact between negative emotions and the level of health-promoting behaviors among college students during their time at the university. Results: ① There were significant differences in the levels of health-promoting behaviors and negative emotions over the course of 7 months (P < 0.05). Health-promoting behaviors were found to have a significant negative correlation with negative emotions (P < 0.05). ② Negative emotions at T1 significantly negatively predicted health-promoting behaviors at T2 (ß = -0.11, P < 0.01), while health-promoting behaviors at T1 significantly negatively predicted negative emotions at T2 (ß = -0.12, P < 0.001). ③ Stress management (ß = -0.104, P < 0.05; ß = -0.087, P < 0.05), self-actualization (ß = -0.282, P < 0.01; ß = -0.260, P < 0.05), health responsibility (ß = -0.057, P < 0.05; ß = -0.088, P < 0.05), and interpersonal relations (ß = 0.068, P < 0.01; ß = 0.138, P < 0.05) were important components in improving stress and anxiety. Self-actualization (ß = -0.437, P < 0.001), exercise (ß = 0.048, P < 0.001), nutrition (ß = 0.044, P < 0.001), and interpersonal relations (ß = 0.065, P < 0.001) were important components in improving depression. ④ Gender, place of household registration, and whether the individual is the only child were significant factors affecting negative emotions in college freshmen. Conclusion: The level of health-promoting behaviors is an important indicator for assessing the negative emotional states of college freshmen. Enhancing health-promoting behaviors across various dimensions can help alleviate different types of negative emotions. Gender, place of household registration, and being the only child are significant factors that influence negative emotions.

trans-Palmitoleic acid promotes adipose thermogenesis to reduce obesity via hypothalamic FFAR1 signaling.

Diet-induced thermogenesis (DIT) is crucial for maintaining body weight homeostasis, and the role of dietary fatty acids in modulating DIT is essential. However, the underlying mechanism of fatty acid regulated diet-induced thermogenesis remains elusive. Utilizing the diet- and genetic ablation-induced obese mice models, we found that the C16 unsaturated fatty acids, trans-palmitoleic acid (TPA) and cis-palmitoleic acid (CPA), significantly increased the energy expenditure by promoting the thermogenesis of brown adipose tissues and the production of beige cells in white adipose. As a result, there is a significant reduction in the occurrence of obesity, associated hepatic steatosis and hyperglycemia. Notably, TPA exhibited more potent effects on promoting DIT and alleviating obesity than CPA did. Using inhibitor and gene deletion mice models, we unveiled that TPA acted as a signaling molecule to play a biological function, which could be sensed by the hypothalamic FFAR1 to activate the sympathetic nervous system in promoting adipose tissue thermogenesis. Together, these results demonstrate the underlying mechanism of free fatty acids associated-DIT and will provide fresh insights into the roles of trans-fatty acids in the development of obesity.

Protein-enriched soup and weekly exercise improve muscle health: A randomized trial in mid-to-old age with inadequate protein intake.

BACKGROUND: Prior research has highlighted the synergistic impact of protein supplementation on muscle function post-exercise in adults; however, evidence supporting the combined effects were less robust and inconsistent on those with protein insufficiency. This investigation aims to explore efficacy of protein-enriched soup coupled with exercise on muscle health and metabolism in middle-aged and older adults with suboptimal protein intake. METHODS: An open-label, 12-week, randomized controlled trial involving participants with insufficient protein intake (<1.0 g/kg/day) was done. The intervention group consumed protein-enriched soup (24-30 g protein daily) and 1-h weekly exercise, while controls received health education. Assessments included laboratory tests, functional assessments, and body composition. RESULTS: In this trial, 97 out of 100 randomized participants (mean age: 64.65 ± 4.84 years, 81.8% female) completed the study (47 in intervention group and 50 in control group). Compared results of baselines, at 1 and 3 months of intervention, significant improvements in waist circumference (83.48 ± 10.22 vs. 82.5 ± 9.88 vs. 82.37 ± 9.42 cm, P for trend = 0.046), 6-min walking distance (525.65 ± 58.46 vs. 534.47 ± 51.87 vs. 552.02 ± 57.66 m, P for trend = 0.001), five-time sit-to-stand time (7.63 ± 1.63 vs. 6.81 ± 1.8 vs. 6.4 ± 1.42 s, P for trend <0.001), grip strength (26.74 ± 6.54 vs. 27.53 ± 6.99 vs. 28.52 ± 7.09 kg, P for trend <0.001), and MNA score (26.8 ± 2.14 vs. 27.73 ± 1.74 vs. 27.55 ± 1.72, P for trend <0.001) were discerned within the intervention group. The intervention demonstrated a significant reduction in serum triglyceride (105.32 ± 49.84 vs. 101.36 ± 42.58 vs. 93.43 ± 41.49 mg/dL, P for trend = 0.023), increased HDL-C (60.04 ± 16.21 vs. 60 ± 17.37 vs. 62.55 ± 18.27 mg/dL, P for trend = 0.02), and DHEA-S levels (97.11 ± 54.39 vs. 103.39 ± 56.75 vs. 106.83 ± 60.56 µg/dL, P for trend = 0.002). Serum myostatin did not differ in both groups, but serum leptin levels significantly increased (9118.88 ± 5811.68 vs. 11508.97 ± 7151.08 vs. 11220.80 ± 7190.71 pg/mL, P for trend = 0.016) in controls. The intervention group showed greater improvements in 6 min walking distance (ß = 0.71, 95% CI: 6.88 to 40.79, P = 0.006), five-time sit-to-stand test (ß = -0.87, 95% CI: -1.59 to -0.15, P = 0.017), MNA score (ß = 0.96, 95% CI: 0.20 to 1.71, P = 0.013), serum triglycerides (ß = -15.01, 95% CI: -27.83 to -2.20, P = 0.022), LDL-C (ß = -9.23, 95% CI: -16.98 to -1.47, P = 0.020), and DHEA-S levels (ß = 9.98, 95% CI: 0.45 to 19.51, P = 0.04) than controls. CONCLUSIONS: Protein-enriched soup with weekly exercise over 12 weeks significantly improved physical performance, lipid profile, and DHEA-S levels among middle-aged and older adults with inadequate protein intake, while studies assessing long-term benefits of the intervention are needed.

A computational framework for predicting novel drug indications using graph convolutional network with contrastive learning.

Inferring potential drug indications plays a vital role in the drug discovery process. It can be time-consuming and costly to discover novel drug indications through biological experiments. Recently, graph learning-based methods have gained popularity for this task. These methods typically treat the prediction task as a binary classification problem, focusing on modeling associations between drugs and diseases within a graph. However, labeled data for drug indication prediction is often limited and expensive to acquire. Contrastive learning addresses this challenge by aligning similar drug-disease pairs and separating dissimilar pairs in the embedding space. Thus, we developed a model called DrIGCL for drug indication prediction, which utilizes graph convolutional networks and contrastive learning. DrIGCL incorporates drug structure, disease comorbidities, and known drug indications to extract representations of drugs and diseases. By combining contrastive and classification losses, DrIGCL predicts drug indications effectively. In multiple runs of hold-out validation experiments, DrIGCL consistently outperformed existing computational methods for drug indication prediction, particularly in terms of top-k. Furthermore, our ablation study has demonstrated a significant improvement in the predictive capabilities of our model when utilizing contrastive learning. Finally, we validated the practical usefulness of DrIGCL by examining the predicted novel indications of Aspirin. The prediction model's code is available at https://github.com/yuxunluo9/DrIGCL.

Determinative scrolling and folding of membranes through shrinking channels.

Flat membranes ubiquitously transform into mysterious complex shapes in nature and artificial worlds. Behind the complexity, clear determinative deformation modes have been continuously found to serve as basic application rules but remain unfulfilled. Here, we decipher two elemental deformation modes of thin membranes, spontaneous scrolling and folding as passing through shrinking channels. We validate that these two modes rule the deformation of membranes of a wide thickness range from micrometer to atomic scale. Their occurrence and the determinative fold number quantitatively correlate with the Föppl-von Kármán number and shrinkage ratio. The unveiled determinative deformation modes can guide fabricating foldable designer microrobots and delicate structures of two-dimensional sheets and provide another mechanical principle beyond genetic determinism in biological morphogens.

Relationship between endoscopic gastroesophageal valve grading and mean nocturnal baseline impedance and postreflux swallow-induced peristaltic wave index in patients with gastroesophageal reflux disease.

This study aimed to investigate the relationship between endoscopic gastroesophageal valve grading and mean nocturnal baseline impedance (MNBI) and postreflux swallow-induced peristaltic wave index (PSPWI) in patients with gastroesophageal reflux disease (GERD). A total of 120 patients diagnosed with GERD disease were included in the study. According to the classification of endoscopic gastroesophageal valves, the patients were divided into 5 groups, group 1 as baseline group, and Group 2-4 as Hill grade I-IV. Basic information about the patients was collected, including age and gender. The mean nocturnal baseline impedance and creep wave index induced by swallowing after rumination were measured by high resolution creep measurement technique. Through statistical analysis, the relationship between valve classification and observation index was discussed. In terms of MNBI, impedance values gradually decreased with increasing valve classification. The average impedance of the Grade 1 group was 23.5 mm Hg/cm2, while the average impedance of the Grade 5 group was 15.2 mm Hg/cm2. This reduction showed a significant decreasing trend (P < .001). In addition, in terms of the peristaltic wave index caused by swallowing after regurgitation, the peristaltic wave index gradually increased with the increase of valve classification. The mean index in the Grade 1 group was 1.8 beats/min, while the mean index in the Grade 5 group was 3.6 beats/min. This increase showed a significant positive relationship (P < .001). Endoscopic gastroesophageal valve grading was significantly correlated with MNBI and PSPWI in patients with GERD. These observations can serve as useful tools for assessing the severity of GERD and monitoring disease progression.

STK16 promoted colorectal cancer progress in a c-MYC signaling-dependent manner.

BACKGROUND: Colorectal cancer standed as a global health challenge, ranking third in cancer incidence and second in cancer-related deaths worldwide. A deeper understanding of the intricate mechanisms driving colorectal cancer development was pressing need. STK16 had garnered attention in recent researches, while its involvement in cancer had been minimally explored. c-MYC had emerged as a key player in cancer biology. Due to its complex structure, multifunctionality, and intricate interactions, directly inhibiting the activity of c-MYC proves to be challenging. Hence, current research was directing efforts towards modulating c-MYC expression levels. METHODS: Immunoblot, Immunohistochemistry and immunoprecipitation assays were conducted to assess the indicated protein expression levels. RT-PCR was performed to detect the corresponding mRNA expression levels. The proliferation, migration, invasion, and colony formation abilities of the specified cancer cells were investigated using CCK8 assays, Brdu assays, transwell assays, and colony formation assays, respectively. Cellular and animal experiments were performed to investigate the correlation between STK16 signaling and c-MYC signaling. RESULTS: STK16 plays a positive regulatory role in the progression of colorectal cancer. Delving into the molecular mechanisms, we unveiled that STK16 phosphorylated c-MYC at serine 452, a pivotal event hindering the ubiquitin-proteasome pathway degradation of c-MYC. Importantly, colorectal cancer proliferation mediated by STK16 was found to be dependent on the phosphorylation of c-MYC at S452. Furthermore, the researchers demonstrated that STK16 knockout or pharmacological inhibition significantly curtailed colorectal cancer proliferation and c-MYC expression in in vivo animal models. CONCLUSION: We discovered that STK16 phosphorylates c-MYC at serine 452, hindering its degradation via the ubiquitin-proteasome pathway. STK16 inhibition, either genetically or pharmacologically, effectively curtails cancer growth and c-MYC expression in vivo. These findings highlight STK16 as a potential therapeutic target for colorectal cancer.

Efficacy and safety of antibiotics for treatment of leptospirosis: a systematic review and network meta-analysis.

BACKGROUND: Leptospirosis, an important zoonotic bacterial disease, commonly affects resource-poor populations and results in significant morbidity and mortality worldwide. The value of antibiotics in leptospirosis remains unclear, as evidenced by the conflicting opinions published. METHODS: We conducted a search in the PubMed, Web of Science, and Cochrane Library databases for studies. These studies included clinical trials and retrospective studies that evaluated the efficacy or safety of antibiotics for leptospirosis treatment. The primary outcomes assessed were defervescence time, mortality rate, and hospital stays. Subgroup analyses were performed based on whether there were cases involving children and whether there were cases of severe jaundice. Safety was defined as the prevalence of adverse events associated with the use of antibiotics. p scores were utilized to rank the efficacy of the antibiotics. RESULTS: There are included 9 randomized controlled trials (RCTs), 1 control trial (CT), and 3 retrospective studies (RS) involving 920 patients and 8 antibiotics. Six antibiotics resulted in significantly shorter defervescence times compared to the control, namely cefotaxime (MD, - 1.88; 95% CI = - 2.60 to - 1.15), azithromycin (MD, - 1.74; 95% CI = - 2.52 to - 0.95), doxycycline (MD, - 1.53; 95% CI = - 2.05 to - 1.00), ceftriaxone (MD, - 1.22; 95% CI = - 1.89 to - 0.55), penicillin (MD, - 1.22; 95% CI = - 1.80 to - 0.64), and penicillin or ampicillin (MD, - 0.08; 95% CI = - 1.01 to - 0.59). The antibiotics were not effective in reducing the mortality and hospital stays. Common adverse reactions to antibiotics included Jarisch-Herxheimer reaction, rash, headache, and digestive reactions (nausea, vomiting, diarrhea, abdominal pain, and others). CONCLUSIONS: Findings recommend that leptospirosis patients be treated with antibiotics, which significantly reduced the leptospirosis defervescence time. Cephalosporins, doxycycline, and penicillin are suggested, and azithromycin may be a suitable alternative for drug-resistant cases. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022354938.

Predicting associations between drugs and G protein-coupled receptors using a multi-graph convolutional network.

Developing new drugs is an expensive, time-consuming process that frequently involves safety concerns. By discovering novel uses for previously verified drugs, drug repurposing helps to bypass the time-consuming and costly process of drug development. As the largest family of proteins targeted by verified drugs, G protein-coupled receptors (GPCR) are vital to efficiently repurpose drugs by inferring their associations with drugs. Drug repurposing may be sped up by computational models that predict the strength of novel drug-GPCR pairs interaction. To this end, a number of models have been put forth. In existing methods, however, drug structure, drug-drug interactions, GPCR sequence, and subfamily information couldn't simultaneously be taken into account to detect novel drugs-GPCR relationships. In this study, based on a multi-graph convolutional network, an end-to-end deep model was developed to efficiently and precisely discover latent drug-GPCR relationships by combining data from multi-sources. We demonstrated that our model, based on multi-graph convolutional networks, outperformed rival deep learning techniques as well as non-deep learning models in terms of inferring drug-GPCR relationships. Our results indicated that integrating data from multi-sources can lead to further advancement.

Identification of Novel FZD4 Mutations in Familial Exudative Vitreoretinopathy and Investigating the Pathogenic Mechanisms of FZD4 Mutations.

Purpose: The purpose of this study is to report five novel FZD4 mutations identified in familial exudative vitreoretinopathy (FEVR) and to analyze and summarize the pathogenic mechanisms of 34 of 96 reported missense mutations in FZD4. Methods: Five probands diagnosed with FEVR and their family members were enrolled in the study. Ocular examinations and targeted gene panel sequencing were conducted on all participants. Plasmids, each carrying 29 previously reported FZD4 missense mutations and five novel mutations, were constructed based on the selection of mutations from each domain of FZD4. These plasmids were used to investigate the effects of mutations on protein expression levels, Norrin/ß-catenin activation capacity, membrane localization, norrin binding ability, and DVL2 recruitment ability in HEK293T, HEK293STF, and HeLa cells. Results: All five novel mutations (S91F, V103E, C145S, E160K, C377F) responsible for FEVR were found to compromise Norrin/ß-catenin activation of FZD4 protein. After reviewing a total of 34 reported missense mutations, we categorized all mutations based on their functional changes: signal peptide mutations, cysteine mutations affecting disulfide bonds, extracellular domain mutations influencing norrin binding, transmembrane domain (TM) 1 and TM7 mutations impacting membrane localization, and intracellular domain mutations affecting DVL2 recruitment. Conclusions: We expanded the spectrum of FZD4 mutations relevant to FEVR and experimentally demonstrated that missense mutations in FZD4 can be classified into five categories based on different functional changes.

Effect of Metabolic Syndrome on Left Atrial and Left Ventricular Deformation and Atrioventricular Interactions in Patients With Myocardial Infarction.

BACKGROUND: Metabolic syndrome (MetS) is associated with worse prognosis in patients with myocardial infarction (MI). However, it is unclear how MetS in MI patients is associated with left atrial (LA) and left ventricular (LV) deformation. PURPOSE: To determine the effect of MetS on LA and LV deformation and atrioventricular interactions in MI patients. STUDY TYPE: Retrospective. POPULATION: One hundred eighty-one MI patients (73 MetS+ and 108 MetS-), 107 age- and sex-matched controls (49 MetS+ and 58 MetS-). FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession (SSFP)/segmented phase-sensitive inversion recovery SSFP sequence. ASSESSMENT: LA strain and strain rates (reservoir, conduit, and active), left atrioventricular coupling index (LACI), and LV geometry and radial, circumferential and longitudinal global peak strains (PS) were compared among groups. STATISTICAL TESTS: Two-way analysis of variance, Spearman and Pearson's correlation coefficients, and multivariable linear regression analysis. P value <0.05 indicated statistical significance. RESULTS: Compared with controls, the MI patients with or without MetS showed impaired LA function (reservoir, conduit, and active) and LV deformation (radial, circumferential, and longitudinal PS) and higher LACI. The MetS+ group had lower LA reservoir and conduit function and LV deformation than MetS- group. The MetS-MI interaction was not statistically significant. Furthermore, multivariable linear regression showed that MetS was independently associated with LA and LV deformation (ß = -0.181 to -0.209) in MI patients; LA function was independently associated with LV circumferential PS (ß = 0.230 to 0.394) and longitudinal PS (ß = 0.189 to 0.420), and LA passive strain and strain rate were negatively associated with LV mass (ß = -0.178 and -0.298). DATA CONCLUSION: MetS may be associated with the LA and LV dysfunction in MI patients. Impaired LV deformation and LV hypertrophy are independently associated with LA dysfunction in MI patients, and the MI patients have higher LACI than controls, suggesting atrioventricular interaction alterations. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: 3.

Heralded Three-Photon Entanglement from a Single-Photon Source on a Photonic Chip.

In the quest to build general-purpose photonic quantum computers, fusion-based quantum computation has risen to prominence as a promising strategy. This model allows a ballistic construction of large cluster states which are universal for quantum computation, in a scalable and loss-tolerant way without feed forward, by fusing many small n-photon entangled resource states. However, a key obstacle to this architecture lies in efficiently generating the required essential resource states on photonic chips. One such critical seed state that has not yet been achieved is the heralded three-photon Greenberger-Horne-Zeilinger (3-GHZ) state. Here, we address this elementary resource gap, by reporting the first experimental realization of a heralded 3-GHZ state. Our implementation employs a low-loss and fully programmable photonic chip that manipulates six indistinguishable single photons of wavelengths in the telecommunication regime. Conditional on the heralding detection, we obtain the desired 3-GHZ state with a fidelity 0.573±0.024. Our Letter marks an important step for the future fault-tolerant photonic quantum computing, leading to the acceleration of building a large-scale optical quantum computer.

Microwave Ablation versus Surgical Resection for US-detected Multifocal T1N0M0 Papillary Thyroid Carcinoma: A 10-Center Study.

Background Microwave ablation (MWA) is currently under preliminary investigation for the treatment of multifocal papillary thyroid carcinoma (PTC) and has shown promising treatment efficacy. Compared with surgical resection (SR), MWA is minimally invasive and could preserve thyroid function. However, a comparative analysis between MWA and SR is warranted to draw definitive conclusions. Purpose To compare MWA and SR for preoperative US-detected T1N0M0 multifocal PTC in terms of overall and 1-, 3-, and 5-year progression-free survival rates and complication rates. Materials and Methods In this retrospective study, 775 patients with preoperative US-detected T1N0M0 multifocal PTC treated with MWA or SR across 10 centers between May 2015 and December 2021 were included. Propensity score matching (PSM) was performed for patients in the MWA and SR groups, followed by comparisons between the two groups. The primary outcomes were overall and 1-, 3-, and 5-year progression-free survival (PFS) rates and complication rates. Results After PSM, 229 patients (median age, 44 years [IQR 36.5-50.5 years]; 179 female) in the MWA group and 453 patients (median age, 45 years [IQR 37-53 years]; 367 female) in the SR group were observed for a median of 20 months (range, 12-74 months) and 26 months (range, 12-64 months), respectively. MWA resulted in less blood loss, shorter incision length, and shorter procedure and hospitalization durations (all P < .001). There was no evidence of differences in overall and 1-, 3-, or 5-year PFS rates (all P > .05) between MWA and SR (5-year rate, 77.2% vs 83.1%; P = .36) groups. Permanent hoarseness (2.2%, P = .05) and hypoparathyroidism (4.0%, P = .005) were encountered only in the SR group. Conclusion There was no evidence of a significant difference in PFS rates between MWA and SR for US-detected multifocal T1N0M0 PTC, and MWA resulted in fewer complications. Therefore, MWA is a feasible option for selected patients with multifocal T1N0M0 PTC. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Georgiades in this issue.

Asymmetric segregation of maternal mRNAs and germline-related determinants in Cephalochordate embryos: implications for the evolution of early patterning events in chordates.

How animal embryos determine their early cell fates is an important question in developmental biology. In various model animals asymmetrically localized maternal transcripts play important roles in axial patterning and cell fate specification. Cephalochordates (amphioxus), which have three living genera (Asymmetron, Epigonichthys, Branchiostoma), are an early branching chordate lineage and thus occupy a key phylogenetic position for understanding the evolution of chordate developmental mechanisms. It has been shown that in the zygote of Brachiostoma amphioxus, which possess bilateral gonads flanking both sides of their trunk region, maternal transcripts of germline determinants form a compact granule. During early embryogenesis this granule is inherited by a single blastomere that subsequently gives rise to a cluster of cells displaying typical characteristics of primordial germ cells (PGC). These PGCs then come to lie in the tailbud region and proliferate during posterior elongation of the larva to join in the gonad anlagen at the ventral tip of the developing myomeres in amphioxus larvae. However, in Asymmetron and Epigonichthys amphioxus, whose gonads are present only on the right side of their body, nothing is known about their PGC development or the cellular/morphogenetic processes resulting in the asymmetric distribution of gonads. Using conserved germline determinants as markers, we show that similarly to Brachiostoma amphioxus, Asymmetron also employ a preformation mechanism to specify their PGCs, suggesting that this mechanism represents an ancient trait dating back to the common ancestor of Cephalochordates. Surprisingly, we found that Asymmetron PGCs are initially deposited on both sides of the body during early larval development; however, the left side PGCs cease to exist in young juveniles, suggesting that PGCs are eliminated from the left body side during larval development or following metamorphosis. This is reminiscent of the PGC development in the sea urchin embryo, and we discuss the implications of this observation for the evolution of developmental mechanisms.

Shank3 deficiency elicits autistic-like behaviors by activating p38α in hypothalamic AgRP neurons.

BACKGROUND: SH3 and multiple ankyrin repeat domains protein 3 (SHANK3) monogenic mutations or deficiency leads to excessive stereotypic behavior and impaired sociability, which frequently occur in autism cases. To date, the underlying mechanisms by which Shank3 mutation or deletion causes autism and the part of the brain in which Shank3 mutation leads to the autistic phenotypes are understudied. The hypothalamus is associated with stereotypic behavior and sociability. p38α, a mediator of inflammatory responses in the brain, has been postulated as a potential gene for certain cases of autism occurrence. However, it is unclear whether hypothalamus and p38α are involved in the development of autism caused by Shank3 mutations or deficiency. METHODS: Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and immunoblotting were used to assess alternated signaling pathways in the hypothalamus of Shank3 knockout (Shank3-/-) mice. Home-Cage real-time monitoring test was performed to record stereotypic behavior and three-chamber test was used to monitor the sociability of mice. Adeno-associated viruses 9 (AAV9) were used to express p38α in the arcuate nucleus (ARC) or agouti-related peptide (AgRP) neurons. D176A and F327S mutations expressed constitutively active p38α. T180A and Y182F mutations expressed inactive p38α. RESULTS: We found that Shank3 controls stereotypic behavior and sociability by regulating p38α activity in AgRP neurons. Phosphorylated p38 level in hypothalamus is significantly enhanced in Shank3-/- mice. Consistently, overexpression of p38α in ARC or AgRP neurons elicits excessive stereotypic behavior and impairs sociability in wild-type (WT) mice. Notably, activated p38α in AgRP neurons increases stereotypic behavior and impairs sociability. Conversely, inactivated p38α in AgRP neurons significantly ameliorates autistic behaviors of Shank3-/- mice. In contrast, activated p38α in pro-opiomelanocortin (POMC) neurons does not affect stereotypic behavior and sociability in mice. LIMITATIONS: We demonstrated that SHANK3 regulates the phosphorylated p38 level in the hypothalamus and inactivated p38α in AgRP neurons significantly ameliorates autistic behaviors of Shank3-/- mice. However, we did not clarify the biochemical mechanism of SHANK3 inhibiting p38α in AgRP neurons. CONCLUSIONS: These results demonstrate that the Shank3 deficiency caused autistic-like behaviors by activating p38α signaling in AgRP neurons, suggesting that p38α signaling in AgRP neurons is a potential therapeutic target for Shank3 mutant-related autism.

Electroacupuncture alters brain network functional connectivity in subacute stroke: A randomised crossover trial.

BACKGROUND: Electroacupuncture (EA) is a promising rehabilitation treatment for upper-limb motor recovery in stroke patients. However, the neurophysiological mechanisms underlying its clinical efficacy remain unclear. This study aimed to explore the immediate modulatory effects of EA on brain network functional connectivity and topological properties. METHODS: The randomized, single-blinded, self-controlled two-period crossover trial was conducted among 52 patients with subacute subcortical stroke. These patients were randomly allocated to receive either EA as the initial intervention or sham electroacupuncture (SEA) as the initial intervention. After a washout period of 24 hours, participants underwent the alternate intervention (SEA or EA). Resting state electroencephalography signals were recorded synchronously throughout both phases of the intervention. The functional connectivity (FC) of the parietofrontal network and small-world (SW) property indices of the whole-brain network were compared across the entire course of the two interventions. RESULTS: The results demonstrated that EA significantly altered ipsilesional parietofrontal network connectivity in the alpha and beta bands (alpha: F = 5.05, P = .011; beta: F = 3.295, P = .047), whereas no significant changes were observed in the SEA group. When comparing between groups, EA significantly downregulated ipsilesional parietofrontal network connectivity in both the alpha and beta bands during stimulation (alpha: t = -1.998, P = .049; beta: t = -2.342, P = .022). Significant differences were also observed in the main effects of time and the group × time interaction for the SW index (time: F = 5.516, P = .026; group × time: F = 6.892, P = .01). In terms of between-group comparisons, the EA group exhibited a significantly higher SW index than the SEA group at the post-stimulation stage (t = 2.379, P = .018). CONCLUSION: These findings suggest that EA downregulates ipsilesional parietofrontal network connectivity and enhances SW properties, providing a potential neurophysiological mechanism for facilitating motor performance in stroke patients.