Optimal Decoding Order and Power Allocation for Sum Throughput Maximization in Downlink NOMA Systems.

In this paper, we consider a downlink non-orthogonal multiple access (NOMA) system over Nakagami-m channels. The single-antenna base station serves two single-antenna NOMA users based on statistical channel state information (CSI). We derive the closed-form expression of the exact outage probability under a given decoding order, and we also deduce the asymptotic outage probability and diversity order in a high-SNR regime. Then, we analyze all the possible power allocation ranges and theoretically prove the optimal power allocation range under the corresponding decoding order. The demarcation points of the optimal power allocation ranges are affected by target data rates and total power, without an effect from the CSI. In particular, the values of the demarcation points are proportional to the total power. Furthermore, we formulate a joint decoding order and power allocation optimization problem to maximize the sum throughput, which is solved by efficiently searching in our obtained optimal power allocation ranges. Finally, Monte Carlo simulations are conducted to confirm the accuracy of our derived exact outage probability. Numerical results show the accuracy of our deduced demarcation points of the optimal power allocation ranges. And the optimal decoding order is not constant at different total transmit power levels.

Ordered mesoporous hairbrush-like nanocarbon assembled microfibers for solid-phase microextraction of benzene series in oilfield sewage.

The development of advanced functional nanomaterials for solid-phase microextraction (SPME) remains an imperative aspect of sample pretreatment. Herein, we introduce a novel SPME fiber consisting of graphene fibers modified with ordered mesoporous carbon nanotubes arrays (CNTAs) tailored for the determination of benzene series in oilfield wastewater, which is synthesized by an ionic liquid-assisted wet spinning process of graphene nanosheets, followed by a precisely controlled growth of metal-organic framework and subsequent pyrolysis treatment. The resulting robust microfiber structure resembles a "hairbrush" configuration, with a crumpled graphene fiber "stem" and high-order mesoporous CNTAs "hairs". This unique architecture significantly enhances the SPME capacity, as validated by gas chromatography-mass spectrometry. The hairbrush-like nanocarbon assembled microfibers possess structural characteristics, a high specific surface area, and numerous binding sites, offering efficient enrichment of benzene series compounds in oilfield wastewater, including benzene, ethylbenzene, m-xylene, p-xylene, and toluene. Our analysis demonstrates that these microfibers exhibit broad linear ranges (0.2-600 µg L-1), low detection limits (0.005-0.03 mg L-1), and excellent repeatability (3.2-5.5% for one fiber, 2.1-6.7% for fiber-to-fiber) for detection. When compared to commercial alternatives, these hairbrush-like nanocarbon-assembled microfibers exhibit significantly enhanced extraction efficiency for benzene series compounds.

Efficacy and safety of bimekizumab in the treatment of psoriatic arthritis: a systematic review and meta-analysis.

BACKGROUND: Bimekizumab, a humanized monoclonal IgG1 antibody targeting both interleukin (IL)-17A and IL-17F, could be effective for treating Psoriatic arthritis (PsA). This study aimed to systematically evaluate the efficacy and safety of bimekizumab in the management of PsA. RESEARCH DESIGN AND METHODS: A comprehensive literature search by August 2023 was performed through PubMed, Embase, Cochrane Controlled Register of Trials, and ClinicalTrials.gov. investigating the efficacy or safety data of bimekizumab in the treatment of PsA. Data was pooled using the random-effects models. Egger tests were used to evaluate potential publication bias. RESULTS: A total of 4 RCTs, involving 892 PsA patients and 467 placebo controls, were included in this analysis. Bimekizumab significantly increased the rates of PASI75 and PASI100 compared with placebos [RR = 7.22, 95% CI (5.24, 9.94), p < 0.001; RR = 10.12, 95% CI (6.00, 17.09), p < 0.001]. The rate of overall adverse events was slightly higher in the bimekizumab group [RR = 1.42, 95% CI (1.05, 1.93) p = 0.023). However, there were fewer adverse severe drug reactions in the bimekizumab group compared to the placebo. CONCLUSION: Bimekizumab had a significant clinical benefit in managing PsA and an acceptable safety profile.

Chromosomal localization of mutated genes in non-syndromic familial thyroid cancer.

Familial non-medullary thyroid carcinoma (FNMTC) is a type of thyroid cancer characterized by genetic susceptibility, representing approximately 5% of all non-medullary thyroid carcinomas. While some cases of FNMTC are associated with familial multi-organ tumor predisposition syndromes, the majority occur independently. The genetic mechanisms underlying non-syndromic FNMTC remain unclear. Initial studies utilized SNP linkage analysis to identify susceptibility loci, including the 1q21 locus, 2q21 locus, and 4q32 locus, among others. Subsequent research employed more advanced techniques such as Genome-wide Association Study and Whole Exome Sequencing, leading to the discovery of genes such as IMMP2L, GALNTL4, WDR11-AS1, DUOX2, NOP53, MAP2K5, and others. But FNMTC exhibits strong genetic heterogeneity, with each family having its own pathogenic genes. This is the first article to provide a chromosomal landscape map of susceptibility genes associated with non-syndromic FNMTC and analyze their potential associations. It also presents a detailed summary of variant loci, characteristics, research methodologies, and validation results from different countries.

A context-dependent perspective to understand the relation between parent-child physiological synchrony and child socioemotional adjustment.

Physiological synchrony is an important biological process during which parent-child interaction plays a significant role in shaping child socioemotional adjustment. The present study held a context-dependent perspective to examine the conditional association between parent-child physiological synchrony and child socioemotional adjustment (i.e., relationship quality with parents and child emotion regulation) under different (i.e., from highly unsupportive to highly supportive) emotional contexts. One hundred and fifty school-age Chinese children (Mage = 8.64 years, 63 girls) and their primary caregivers participated in this study. After attaching electrocardiogram (ECG) electrodes, parent-child dyads were instructed to complete a 4-minute conflict discussion task. Parent-child physiological synchrony was calculated based on the within-dyad association between parents' and children's respiratory sinus arrhythmia (RSA) levels across eight 30-second epochs. Parental emotional support, child relationship quality with parents, and child emotion regulation during the discussion task were coded by trained research assistants. Supporting our hypotheses, parental emotional support moderated the relations of parent-child RSA synchrony with both child relationship quality with parents and child emotion regulation. Furthermore, the Johnson-Neyman technique of moderation indicated that the associations between parent and child RSA synchrony and child socioemotional adjustment indicators shifted from negative to positive as the parental emotional support became increasingly high. Our findings suggest that parent-child physiological synchrony may not be inherently adaptive or maladaptive, highlighting the importance of understanding the function of parent-child physiological synchrony under specific contexts. RESEARCH HIGHLIGHTS: Physiological synchrony may not be inherently adaptive or maladaptive, and the meanings of parent-child physiological synchrony might be contingent on contextual factors. Parental emotional support moderated the relations between parent-child respiratory sinus arrhythmia (RSA) synchrony and child socioemotional adjustment indicators (i.e., child relationship quality with parents and child emotion regulation). More positive/less negative parent-child RSA synchrony was associated with better child socioemotional adjustment under a supportive emotional context, whereas with poorer child socioemotional adjustment under an unsupportive emotional context. These findings highlight the significance of considering the emotional context in physiological synchrony studies.

Ambient Air Pollution and Vision Disorder: A Systematic Review and Meta-Analysis.

The effects of air pollution on physical health are well recognized, with many studies revealing air pollution's effects on vision disorder, yet no relationship has been established. Therefore, a meta-analysis was carried out in this study to investigate the connection between vision disorder and ambient particles (diameter ≤ 2.5 µm (PM2.5), diameter ≤ 10 µm (PM10)) and gaseous pollutants (nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), Ozone (O3)). Twelve relevant studies published by 26 February 2024 were identified in three databases. A pooled odds ratios (ORs) of 95% confidence intervals (CIs) were obtained using random-effects meta-analysis models. Meta-analysis results revealed that for every 10 µg/m3 increase in PM2.5 and NO2 exposure, a substantially higher incidence of vision disorder was observed (OR = 1.10; 95% CI: 1.01, 1.19; OR = 1.08, 95% CI: 1.00, 1.16). No significant correlation existed between exposure to PM10, SO2 and CO and vision disorder. However, O3 exposure was negatively associated with vision disorder. In addition, subgroup analyses revealed that PM2.5 exposure was significantly correlated with the risk of glaucoma and age-related macular degeneration and that children and adolescents were more susceptible to NO2 and PM2.5 than adults. Overall, exposure to air pollutants, especially PM2.5 and NO2, may increase the incidence of vision disorder.

Peer Stress Spills Over to Family Stress in the Context of Emotion Regulation Difficulties: A Daily Diary Study with Chinese Adolescents.

Conflict in peer and family relationships becomes more common in the adolescent period when compared to previous developmental periods. These typical developmental challenges can be exacerbated in the context of poor emotion regulation skills. Using daily diary data, the current study examined the stress spillover effects of peer and family stress on one another, as well as the moderating role of emotion regulation challenges (i.e., emotional inhibition, dysregulation). A sample of 310 Chinese adolescents (Mage = 13.02 years, SD = 0.76 years, 50.7% boys) completed an initial measure of emotion regulation difficulties, then reported on peer and family stress for 10 consecutive weekdays. Results indicated that there was an overall same-day peer stress spillover effect in which adolescents' peer stress on a given day was negatively associated with later conflictual interactions with their parents. Further, the relation between peer stress and same- and next-day family stress was exacerbated in the context of high levels of emotional inhibition. Family stress did not significantly relate to next-day peer stress, nor was this association moderated by difficulties with emotion regulation. These results highlight the temporal sequence of daily peer-to-family stress spillover. Though emotional inhibition may be culturally adaptive for maintaining interpersonal harmony, it can be maladaptive in managing stress for Chinese adolescents.

Screening and evaluation of antioxidants for retinal pigment epithelial cell protection: L-ergothioneine as a novel therapeutic candidate through NRF2 activation.

The continual exposure of retinal tissues to oxidative stress leads to discernible anatomical and physiological alterations. Specifically, the onslaught of oxidative damage escalates the irreversible death of retinal pigmented epithelium (RPE) cells, pinpointed as the fundamental pathological event in dry age-related macular degeneration (AMD). There is a conspicuous lack of effective therapeutic strategies to counteract this degenerative process. This study screened a library of antioxidants for their ability to protect RPE cells against oxidative stress and identified L-ergothioneine (EGT) as a potent cytoprotective agent. L-ergothioneine provided efficient protection against oxidative stress-damaged RPE and maintained cell redox homeostasis and normal physiological functions. It maintained the normal structure of the retina in mice under oxidative stress conditions. Transcriptomic analysis revealed that EGT counteracted major gene expression changes induced by oxidative stress. It upregulated antioxidant gene expression and inhibited NRF2 translocation. The inhibition of NRF2 abolished EGT's protective effects, suggesting that NRF2 activation contributes to its mechanism of action. In conclusion, we identified EGT as a safe and effective small-molecule compound that is expected to be a novel antioxidative agent for treating AMD.

White Matter Plasticity Underpins Cognitive Gains After Multidomain Adaptive Computerized Cognitive Training.

BACKGROUND: This study aims to evaluate the effectiveness of computerized cognitive training (CCT) on white matter (WM) neuroplasticity and neuropsychological performance. METHODS: A total of 128 community older adults (64.36 ±â€…6.14 years) were recruited and randomly assigned to the intervention or control group. Participants in the intervention group received a home-based, multidomain, and adaptive CCT for 30 minutes, 2 days per week for 1 year. Neuropsychological assessments, diffusion magnetic resonance imaging (MRI), and T1-weighted structural MRI were performed at the pre- and post-intervention visits. RESULTS: Eighty-one of 128 participants (41 in the intervention group and 40 in the control group) completed the 1-year intervention, and 61 of them (27 in the intervention group and 34 in the control group) underwent MRI scans twice. After excluding attrition bias, a significant time-by-group interaction on the Stroop Color-Word Test (SCWT; F = 51.85, p < .001) was found, showing improvement in the intervention group and a decline in the control group. At the brain level, the intervention group exhibited increased axial diffusivity in the left posterior thalamic radiation, and this increase was significantly correlated with reduced SCWT reaction time (r = ‒0.42, p = .029). No significant time-by-group interactions were found for gray matter volume. CONCLUSIONS: Our findings suggest that conducting multidomain adaptive CCT is an effective and feasible method to counteract cognitive decline in older adults, with WM neuroplasticity underpinning cognitive improvements. This study contributes to the understanding of the neural basis for the beneficial effect of CCT for older adults.

Identification of P21 (CDKN1A) Activated Kinase 4 as a Susceptibility Gene for Familial Non-Medullary Thyroid Carcinoma.

Background: Familial non-medullary thyroid carcinoma (FNMTC) is a genetically predisposed disease with unclear genetic mechanisms. This makes research on susceptibility genes important for the diagnosis and treatment options. Methods: This study included a five-member family affected by papillary thyroid carcinoma. The candidate genes were identified through whole-exome sequencing and Sanger sequencing in family members, other FNMTC patients, and sporadic non-medullary thyroid carcinoma patients. The pathogenicity of the mutation was predicted using in silico tools. Cell phenotype experiments in vitro and models of lung distant metastasis in vivo were conducted to confirm the characteristics of the mutation. Transcriptome sequencing and mechanistic validation were employed to compare the disparities between PAK4 wild-type (WT) and PAK4 mutant (MUT) cell lines. Results: This mutation alters the protein structure, potentially increasing instability by affecting hydrophobicity, intra-molecular hydrogen bonding, and phosphorylation sites. It specifically promotes phosphorylated PAK4 nuclear translocation and expression in thyroid tissue and cell lines. Compared with the WT cells line, PAK4 I417T demonstrates enhanced proliferation, invasiveness, accelerated cell division, and inhibition of cell apoptosis in vitro. In addition, it exhibits a significant propensity for metastasis in vivo. It activates tumor necrosis factor signaling through increased phosphorylation of PAK4, JNK, NFκB, and c-Jun, unlike the WT that activates it via the PAK4-NFκ-MMP9 axis. In addition, PAK4 MUT protein interacts with matrix metalloproteinase (MMP)3 and regulates MMP3 promoter activity, which is not observed in the WT. Conclusions: Our study identified PAK4: c.T1250C: p.I417T as a potential susceptibility gene for FNMTC. The study concludes that the mutant form of PAK4 exhibits oncogenic function, suggesting its potential as a novel diagnostic molecular marker for FNMTC.

Distinct patterns of grandparental involvement in childrearing and Chinese preschoolers' social-emotional development.

Grandparental involvement in childrearing has been associated with children's social-emotional development, yet findings are mixed. Grandparental involvement is a multidimensional concept that includes both quantity (i.e., the degree of grandparental involvement) and quality aspects (i.e., the quality of parent-grandparent coparenting and the quality of grandparenting practices). This study included both quantity and quality aspects to identify heterogeneous patterns of grandparental involvement and examined the associations between distinct patterns of grandparental involvement and children's social-emotional outcomes. Participants were 428 families with Chinese preschoolers (Mage = 53.75 months, SD = 10.32; 51.4% boys). Primary parental and grandparental caregivers completed the questionnaires. Four patterns of grandparental involvement emerged: the low-involvement mediocre-quality, the median, the high-involvement uneven-quality, and the high-involvement high-quality groups. Heterogeneous patterns of grandparental involvement exist and are differentially associated with children's social-emotional development. Children with grandparents in the high-involvement high-quality group demonstrated higher levels of social skills than those in the low-involvement mediocre-quality group and the high-involvement uneven-quality group. They also showed the lowest level of problem behaviors. This study highlights variations in grandparental involvement and helps to clarify previous inconsistent findings regarding the role of grandparental involvement in child development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The single-cell transcriptomic atlas and RORA-mediated 3D epigenomic remodeling in driving corneal epithelial differentiation.

Proper differentiation of corneal epithelial cells (CECs) from limbal stem/progenitor cells (LSCs) is required for maintenance of ocular homeostasis and clear vision. Here, using a single-cell transcriptomic atlas, we delineate the comprehensive and refined molecular regulatory dynamics during human CEC development and differentiation. We find that RORA is a CEC-specific molecular switch that initiates and drives LSCs to differentiate into mature CECs by activating PITX1. RORA dictates CEC differentiation by establishing CEC-specific enhancers and chromatin interactions between CEC gene promoters and distal regulatory elements. Conversely, RORA silences LSC-specific promoters and disrupts promoter-anchored chromatin loops to turn off LSC genes. Collectively, our work provides detailed and comprehensive insights into the transcriptional dynamics and RORA-mediated epigenetic remodeling underlying human corneal epithelial differentiation.

Structural basis of the subcortical maternal complex and its implications in reproductive disorders.

The subcortical maternal complex (SCMC) plays a crucial role in early embryonic development. Malfunction of SCMC leads to reproductive diseases in women. However, the molecular function and assembly basis for SCMC remain elusive. Here we reconstituted mouse SCMC and solved the structure at atomic resolution using single-particle cryo-electron microscopy. The core complex of SCMC was formed by MATER, TLE6 and FLOPED, and MATER embraced TLE6 and FLOPED via its NACHT and LRR domains. Two core complexes further dimerize through interactions between two LRR domains of MATERs in vitro. FILIA integrates into SCMC by interacting with the carboxyl-terminal region of FLOPED. Zygotes from mice with Floped C-terminus truncation showed delayed development and resembled the phenotype of zygotes from Filia knockout mice. More importantly, the assembly of mouse SCMC was affected by corresponding clinical variants associated with female reproductive diseases and corresponded with a prediction based on the mouse SCMC structure. Our study paves the way for further investigations on SCMC functions during mammalian preimplantation embryonic development and reveals underlying causes of female reproductive diseases related to SCMC mutations, providing a new strategy for the diagnosis of female reproductive disorders.

Self-Cascade Nanozyme Reactor as a Cuproptosis Inducer Synergistic Inhibition of Cellular Respiration Boosting Radioimmunotherapy.

Intrinsic or acquired radioresistance remained an important challenge in the successful management of cancer. Herein, a novel "smart" multifunctional copper-based nanocomposite (RCL@Pd@CuZ) to improve radiotherapy (RT) sensitivity is designed and developed. In this nanoplatform, DSPE-PEG-RGD modified on the liposome surface enhanced tumor targeting and permeability; capsaicin inserted into the phospholipid bilayer improved the hypoxic conditions in the tumor microenvironment (TME) by inhibiting mitochondrial respiration; a Cu MOF porous cube encapsulated in liposome generated highly active hydroxyl radicals (OH·), consumed GSH and promoted cuproptosis by releasing Cu2+ ; the ultrasmall palladium (Pd) nanozyme within the cubes exhibited peroxidase activity, catalyzing toxic OH· generation and releasing oxygen from hydrogen peroxide; and lastly, Pd, as an element with a relatively high atomic number (Z) enhanced the photoelectric and Compton effects of X-rays. Therefore, RCL@Pd@CuZ enhance RT sensitivity by ameliorating hypoxia, promoting cuproptosis, depleting GSH, amplifying oxidative stress, and enhancing X-ray absorption  , consequently potently magnifying immunogenic cell death (ICD). In a mouse model , RCL@Pd@CuZ combined with RT yielded >90% inhibition compared with that obtained by RT alone in addition to a greater quantity of DC maturation and CD8+ T cell infiltration. This nanoplatform offered a promising remedial modality to facilitate cuproptosis-related cancer radioimmunotherapy.

Parenting links to parent-child interbrain synchrony: a real-time fNIRS hyperscanning study.

Parent-child interaction is crucial for children's cognitive and affective development. While bio-synchrony models propose that parenting influences interbrain synchrony during interpersonal interaction, the brain-to-brain mechanisms underlying real-time parent-child interactions remain largely understudied. Using functional near-infrared spectroscopy, we investigated interbrain synchrony in 88 parent-child dyads (Mage children = 8.07, 42.0% girls) during a collaborative task (the Etch-a-Sketch, a joint drawing task). Our findings revealed increased interbrain synchrony in the dorsolateral prefrontal cortex and temporo-parietal areas during interactive, collaborative sessions compared to non-interactive, resting sessions. Linear regression analysis demonstrated that interbrain synchrony in the left temporoparietal junction was associated with enhanced dyadic collaboration, shared positive affect, parental autonomy support, and parental emotional warmth. These associations remained significant after controlling for demographic variables including child age, child gender, and parent gender. Additionally, differences between fathers and mothers were observed. These results highlight the significant association between brain-to-brain synchrony in parent-child dyads, the quality of the parent-child relationship, and supportive parenting behaviors. Interbrain synchrony may serve as a neurobiological marker of real-time parent-child interaction, potentially underscoring the pivotal role of supportive parenting in shaping these interbrain synchrony mechanisms.

Atypical child-parent neural synchrony is linked to negative family emotional climate and children's psychopathological symptoms.

[Correction Notice: An Erratum for this article was reported in Vol 79(2) of American Psychologist (see record 2024-62662-005). In the article "Atypical Child-Parent Neural Synchrony Is Linked to Negative Family Emotional Climate and Children's Psychopathological Symptoms," by Haowen Su, Christina B. Young, Zhuo Rachel Han, Jianjie Xu, Bingsen Xiong, Zisen Zhou, Jingyi Wang, Lei Hao, Zhi Yang, Gang Chen, and Shaozheng Qin (American Psychologist, 2024, Vol. 79, No. 2, pp. 210-224, https://doi.org/10.1037/amp0001173), Figure 2 and its caption were corrected to fix a mismatch between the r coefficients and scatterplots. The caption was changed from "(c) Child-parent hippocampal activity concordance was significantly higher for boundary than nonboundary event time series (Z = 2.30, p = .01). (d) Child-parent vmPFC activity concordance was marginally significantly higher for boundary than nonboundary time series (Z = -1.39, p = .08)" to "(c) Child-parent vmPFC activity concordance was marginally significantly lower for boundary than nonboundary time series (Z = -1.39, p = .08). (d) Child- parent hippocampal activity concordance was significantly higher for boundary than nonboundary event time series (Z = 2.30, p = .01)." In addition, in the second sentence of the second paragraph of the "Reduced Child-Parent vmPFC Connectivity With the Hippocampus Links to Negative Family Emotional Climate and Children's Internalizing Symptoms" section, "anxious/depressed" and "internalizing" were switched. All versions of this article have been corrected.] Family emotional climate is fundamental to children's well-being and mental health. Family environments filled with negative emotions may lead to increased psychopathological symptoms in the child through dysfunctional child-parent interactions. Single-brain paradigms have uncovered changes in brain systems and networks related to negative family environments, but how the neurobiological reciprocity between child and parent brains is associated with children's psychopathological symptoms remains unknown. Here, we first investigated the relation between family emotional climate and children's psychopathological symptoms in 395 child-parent dyads. Using a naturalistic movie-watching functional magnetic resonance imaging technique in a subsample of 50 child-parent dyads, we further investigated the neurobiological underpinnings of how family emotional climates are associated with children's psychopathological symptoms through child-parent neural synchrony. Children from negative family emotional climate experienced significantly more severe psychopathological symptoms. In comparison to child-stranger dyads, child-parent dyads exhibited higher intersubject correlations in the dorsal and ventral portions of the medial prefrontal cortex (mPFC), and greater concordance of activity with widespread regions critical for socioemotional skills. Critically, negative family emotional climate was associated with decreased intersubject functional correlation between the ventral-mPFC and the hippocampus during movie watching in child-parent dyads, which further accounted for higher children's internalizing symptoms. Together, our findings provide insights into the neurobiological mechanisms that negative family environments can cause and maintain psychopathological symptoms in children through atypical child-parent neural synchrony. This has important implications for a better understanding of how child-parent connections may mediate the relation between environmental risks and developmental outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Respiratory sinus arrhythmia (RSA) dynamics matter for children's emotion regulation: RSA inertia and instability within a stress task.

The present study employed two key dynamic indicators (i.e., inertia and instability) to the psychophysiological research of child emotion regulation (ER) and examined whether respiratory sinus arrhythmia (RSA) dynamics were associated with child ER during a stress task. Eighty-nine Chinese school-age children (Mage = 8.77 years, SD = 1.80 years; 46.1% girls) and their primary caregivers participated in the study. After controlling for RSA static reactivity, multiple regression analyses indicated that lower RSA inertia was related to fewer in-task negative emotions rated by children and their caregivers, and higher RSA instability was associated with better child trait ER. This study introduces physiological indicators of the dynamic aspects of parasympathetic activity to the study of child ER.

Family history of malignant or benign thyroid tumors: implications for surgical procedure management and disease-free survival.

Background: Current guidelines lack a standardized management for patients with family history of thyroid carcinoma (fTC),particularly benign thyroid neoplasm (fBTN). Our objective was to investigate the influence of various family histories on the selection of surgical approaches and disease-free survival (DFS). Methods: A cohort study was conducted involving 2261 patients diagnosed with differentiated thyroid carcinoma including those with fTC (n=224), fBTN (n=122), and individuals without a family history of thyroid carcinoma (nfTC; n=1915). Clinicopathological characteristics were collected. DFS was estimated using Kaplan-Meier analysis and factors affecting DFS were identified using Cox proportional hazard model. Results: Compared to nfTC, small tumor size, clinically lymph node-positive, extrathyroidal extension, vascular invasion, Hashimoto's disease and nodular goiter were more common in fTC and fBTN groups. They had lower T stage and a lower rate of good response to TSH suppression therapy but received more radioiodine therapy. It is worth noting that fTC is associated with male, bilateral and multifocal tumors, as well as central lymph node metastasis and distant metastasis. Both fTC (aHR = 2.45, 95% CI=1.11-5.38; P = 0.03) and fBTN (aHR = 3.43, 95% CI=1.27-9.29; P = 0.02) were independent predictors of DFS in patients who underwent lobectomy, but not total thyroidectomy. For 1-4 cm thyroid carcinomas with clinically node-negative, fTC was identified as an independent predictor, whereas fBTN was not. Conclusion: Our findings indicate that a family history, particularly of malignancy, is associated with a more aggressive disease. Family history does not affect the prognosis of patients who undergo total thyroidectomy, but it may increase the risk of postoperative malignant events in those who have a lobectomy. Additionally, it may be necessary to monitor individuals with a family history of benign thyroid neoplasms.

NRG1 Regulates Proliferation, Migration and Differentiation of Human Limbal Epithelial Stem Cells.

Limbal epithelial stem/progenitor cells (LESCs) proliferate, migrate and differentiate into mature corneal epithelium cells (CECs) that cover the ocular surface. LESCs play a crucial role in the maintenance and regeneration of the corneal epithelium, and their dysfunction can lead to various corneal diseases. Neuregulin 1 (NRG1) is a member of the epidermal growth factor family that regulates the growth and differentiation of epithelial tissues. Here, we depicted the dynamic transcriptomic profiles during human CEC differentiation, identifying six gene co-expression modules that were specific to different differentiation stages. We found that the expression of NRG1 was high in human LESCs and decreased dramatically upon differentiation. Knockdown of NRG1 significantly inhibited LESC proliferation and upregulated the expression of the terminal differentiation marker genes KRT3, KRT12 and CLU. In addition, the scratch wound closure assay showed that knockdown of NRG1 attenuated wound closure of LESCs over 24 h. Together, we dissected the transcriptional regulatory dynamics during CEC differentiation and identified NRG1 as a key regulator that promoted LESC proliferation and migration and maintained the undifferentiated state.

Association of PD-L1 Expression with Clinicopathologic Characters in Gastric Cancer: A Comprehensive Meta-analysis.

PURPOSE: The expression level of programmed death ligand-1(PD-L1) in patients with gastric cancer is the key to determining the use of immune drugs. The relationship between PD-L1 expression level and clinical characteristics is worth exploring. METHODS: By setting the search terms correlated to PD-L1 and gastric cancer, a nearly comprehensive search was carried out in four major databases, and the deadline for searching was September 1, 2022. The retrieved documents were further screened by strict inclusion and exclusion criteria after removing the duplication. Next, the quality of the included studies was evaluated with the Newcastle-Ottawa Scale (NOS) scale. Finally, the STATA15.1 software was used to process data and draw plots, and the odds ratios (ORs) were adopted to assess the pooled effect size. RESULTS: A total of 85 works of literature were included in this study through screening strictly, and detailed data were extracted after evaluating the quality of the literature. The process of analysis was conducted in the whole population, Asia-Africa population, European and American population, and Asian population with CPS≥1, amd all found that the expression of PD-L1 in gastric cancer was correlated with age, tumor size, EBV infection, Her-2 expression and microsatellite status. However, the subgroup of the region also found some differences in Asian and Western regions, which was interesting and worth studying further. The included research of this study did not have significant publish bias. CONCLUSION: After careful analysis, this study found that age (>60 years), tumor size (>5cm), EBV infection (+), Her-2 expression (+), microsatellite status (MSI), and mismatch repair status (dMMR) were risk factors for positive expression of PD-L1 in gastric cancer.