Exploring near-infrared autofluorescence properties in parathyroid tissue: an analysis of fresh and paraffin-embedded thyroidectomy specimens.

Significance: Near-infrared autofluorescence (NIRAF) utilizes the natural autofluorescence of parathyroid glands (PGs) to improve their identification during thyroid surgeries, reducing the risk of inadvertent removal and subsequent complications such as hypoparathyroidism. This study evaluates NIRAF's effectiveness in real-world surgical settings, highlighting its potential to enhance surgical outcomes and patient safety. Aim: We evaluate the effectiveness of NIRAF in detecting PGs during thyroidectomy and central neck dissection and investigate autofluorescence characteristics in both fresh and paraffin-embedded tissues. Approach: We included 101 patients diagnosed with papillary thyroid cancer who underwent surgeries in 2022 and 2023. We assessed NIRAF's ability to locate PGs, confirmed via parathyroid hormone assays, and involved both junior and senior surgeons. We measured the accuracy, speed, and agreement levels of each method and analyzed autofluorescence persistence and variation over 10 years, alongside the expression of calcium-sensing receptor (CaSR) and vitamin D. Results: NIRAF demonstrated a sensitivity of 89.5% and a negative predictive value of 89.1%. However, its specificity and positive predictive value (PPV) were 61.2% and 62.3%, respectively, which are considered lower. The kappa statistic indicated moderate to substantial agreement (kappa = 0.478; P < 0.001 ). Senior surgeons achieved high specificity (86.2%) and PPV (85.3%), with substantial agreement (kappa = 0.847; P < 0.001 ). In contrast, junior surgeons displayed the lowest kappa statistic among the groups, indicating minimal agreement (kappa = 0.381; P < 0.001 ). Common errors in NIRAF included interference from brown fat and eschar. In addition, paraffin-embedded samples retained stable autofluorescence over 10 years, showing no significant correlation with CaSR and vitamin D levels. Conclusions: NIRAF is useful for PG identification in thyroid and neck surgeries, enhancing efficiency and reducing inadvertent PG removals. The stability of autofluorescence in paraffin samples suggests its long-term viability, with false positives providing insights for further improvements in NIRAF technology.

Intentional learning establishes multiple attentional sets that simultaneously guide attention.

One of the key human cognitive capabilities is to extract regularities from the environment to guide behavior. An attentional set for a target feature can be established through statistical learning of probabilistic target associations; however, whether an array of attentional sets of predictive target features can be established during intentional learning, and how they might guide attention, is not known yet. To address these questions, we had human observers perform a visual search task where we instructed them to try to use color to find their target shape. We structured the task with a fine-grained statistical regularity such that the target shapes appeared in different colors with five unique probabilities (i.e., 33%, 26%, 19%, 12%, and 5%) while we recorded their electroencephalogram. Observers rapidly learned these regularities, evidenced by being faster to report targets that appeared in higher probability colors. These effects were not due to unequal sample sizes or simple feature priming. More importantly, equivalent speeding across a set of high-probability colors suggests that the brain was driving attention to multiple targets simultaneously. Our electrophysiological results showed larger amplitude N2 posterior contralateral component, indexing perceptual attention, and late positive complex (LPC) component, indexing postperceptual processes, for targets paired with high-probability colors. These electrophysiological data suggest that the learned attentional sets change both perceptual selection and how postperceptual decisions are made. In sum, we show that multiple attentional sets can be established during intentional learning that accompanies general task acquisition and that these attentional sets can simultaneously guide attention by enhancing both perceptual attention and postperceptual processes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Crystalline silica-induced recruitment and immuno-imbalance of CD4+ tissue resident memory T cells promote silicosis progression.

Occupational crystalline silica (CS) particle exposure leads to silicosis. The burden of CS-associated disease remains high, and treatment options are limited due to vague mechanisms. Here we show that pulmonary CD4+ tissue-resident memory T cells (TRM) accumulate in response to CS particles, mediating the pathogenesis of silicosis. The TRM cells are derived from peripheral lymphocyte recruitment and in situ expansion. Specifically, CD69+CD103+ TRM-Tregs depend more on circulating T cell replenishment. CD69 and CD103 can divide the TRM cells into functionally distinct subsets, mirroring the immuno-balance within CD4+ TRM cells. However, targeting CD103+ TRM-Tregs do not mitigate disease phenotype since the TRM subsets exert immunosuppressive but not pro-fibrotic roles. After identifying pathogenic CD69+CD103- subsets, we highlight IL-7 for their maintenance and function, that present a promising avenue for mitigating silicosis. Together, our findings highlight the distinct role of CD4+ TRM cells in mediating CS-induced fibrosis and provide potential therapeutic strategies.

Hydrolyzed conchiolin protein inhibits melanogenesis through PKA/CREB and MEK/ERK signalling pathways.

OBJECTIVE: Hydrolyzed conchiolin protein (HCP) derived from pearl and nacre extracts exerts skin-lightening effects; however, the underlying molecular mechanisms are not fully understood. Herein, we investigated the effect of HCP on melanogenesis and the signalling pathways involved. METHODS: B16F10 cells and PIG cells were treated with HCP to verify its ability to inhibit melanin. Western Blot, immunofluorescence, and flow cytometry methods were performed to investigate the effect of HCP on melanogenesis signalling pathway proteins. The inhibitors were used to further validate the effect of HCP on PKA/CREB and MEK/ERK signalling pathways. To further evaluate the whitening ability of HCP, changes in melanin were detected using 3D melanin skin model and zebrafish model. RESULTS: HCP was found to significantly inhibit melanin synthesis and decrease the expression of melanogenesis-related proteins, such as microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein-2, in a dose-dependent manner. Additionally, we revealed that HCP suppresses melanogenesis via the regulation of the PKA/cAMP response element-binding (CREB) and MEK/extracellular signalling-regulated kinase (ERK) signalling pathways. Using 3D melanin skin models, we demonstrated that HCP can achieve skin-lightening effects by improving apparent chroma, increasing apparent brightness, and inhibiting melanin synthesis. Furthermore, HCP exhibits skin-whitening effects in a zebrafish model. CONCLUSION: These results suggest that HCP suppresses the melanogenesis signalling cascade by inhibiting the PKA/CREB, MEK/ERK signalling pathway and downregulating MITF and its downstream signalling pathways, resulting in decreased melanin synthesis. In summary, HCP is a potential anti-pigmentation agent with promising applications in cosmetics and pharmaceutical products.

OBJECTIF: La protéine conchioline hydrolysée (HCP) dérivée des extraits de perle et de nacre exerce des effets éclaircissants sur la peau ; cependant, les mécanismes moléculaires sous­jacents ne sont pas entièrement compris. Dans cette étude, nous avons investigué l'effet de la HCP sur la mélanogenèse et les voies de signalisation impliquées. MÉTHODES: Les cellules B16F10 et PIG ont été traitées avec la HCP pour vérifier sa capacité à inhiber la mélanine. Des méthodes de Western Blot, d'immunofluorescence et de cytométrie en flux ont été réalisées pour étudier l'effet de la HCP sur les protéines des voies de signalisation de la mélanogenèse. Les inhibiteurs ont été utilisés pour valider davantage l'effet de la HCP sur les voies de signalisation PKA/CREB et MEK/ERK. Pour évaluer plus en détail la capacité éclaircissante de la HCP, les changements de mélanine ont été détectés en utilisant un modèle de peau en 3D de mélanine et un modèle de poisson­zèbre. RÉSULTATS: Il a été constaté que la HCP inhibe significativement la synthèse de la mélanine et diminue l'expression des protéines liées à la mélanogenèse, telles que le facteur de transcription associé à la microphthalmie (MITF), la tyrosinase et la protéine liée à la tyrosinase­2, de manière dose­dépendante. De plus, nous avons révélé que la HCP supprime la mélanogenèse via la régulation des voies de signalisation PKA/cAMP et MEK/ERK. En utilisant des modèles de peau en 3D de mélanine, nous avons démontré que la HCP peut atteindre des effets éclaircissants sur la peau en améliorant la chroma apparente, en augmentant la luminosité apparente et en inhibant la synthèse de la mélanine. En outre, la HCP présente des effets éclaircissants sur la peau dans un modèle de poisson­zèbre. CONCLUSION: Ces résultats suggèrent que la HCP supprime la cascade de signalisation de la mélanogenèse en inhibant les voies de signalisation PKA/CREB et MEK/ERK et en régulant à la baisse le MITF et ses voies de signalisation en aval, ce qui entraîne une diminution de la synthèse de la mélanine. En résumé, la HCP est un agent potentiel anti­pigmentation avec des applications prometteuses dans les produits cosmétiques et pharmaceutiques.

Enhancing Swimming Performance of Magnetic Helical Microswimmers by Surface Microstructure.

Artificial bacterial flagella (ABF), also known as a magnetic helical microswimmer, has demonstrated enormous potential in various future biomedical applications (e.g., targeted drug delivery and minimally invasive surgery). Nevertheless, when used for in vivo/in vitro treatment applications, it is essential to achieve the high motion efficiency of the microswimmers for rapid therapy. In this paper, inspired by microorganisms, the surface microstructure was introduced into ABFs to investigate its effect on the swimming behavior. It was confirmed that compared with smooth counterparts, the ABF with surface microstructure reveals a smaller forward velocity below the step-out frequency (i.e., the frequency corresponding to the maximum velocity) but a larger maximum forward velocity and higher step-out frequency. A hydrodynamic model of microstructured ABF is employed to reveal the underlying movement mechanism, demonstrating that the interfacial slippage and the interaction between the fluid and the microstructure are essential to the swimming behavior. Furthermore, the effect of surface wettability and solid fraction of microstructure on the swimming performance of ABFs was investigated experimentally and analytically, which further reveals the influence of surface microstructure on the movement mechanism. The results present an effective approach for designing fast microrobots for in vivo/in vitro biomedical applications.

Prion protein E219K polymorphism: from the discovery of the KANNO blood group to interventions for human prion disease.

KANNO is a new human blood group that was recently discovered. The KANNO antigen shares the PRNP gene with the prion protein and the prion protein E219K polymorphism determines the presence or absence of the KANNO antigen and the development of anti-KANNO alloantibodies. These alloantibodies specifically react with prion proteins, which serve as substrates for conversion into pathological isoforms in some prion diseases and may serve as effective targets for resisting prion infection. These findings establish a potential link between the KANNO blood group and human prion disease via the prion protein E219K polymorphism. We reviewed the interesting correlation between the human PRNP gene's E219K polymorphism and the prion proteins it expresses, as well as human red blood cell antigens. Based on the immune serological principles of human blood cells, the prion protein E219K polymorphism may serve as a foundation for earlier molecular diagnosis and future drug development for prion diseases.

Multifunctional Hydrogel with 3D Printability, Fluorescence, Biodegradability, and Biocompatibility for Biomedical Microrobots.

As micron-sized objects, mobile microrobots have shown significant potential for future biomedical applications, such as targeted drug delivery and minimally invasive surgery. However, to make these microrobots viable for clinical applications, several crucial aspects should be implemented, including customizability, motion-controllability, imageability, biodegradability, and biocompatibility. Developing materials to meet these requirements is of utmost importance. Here, a gelatin methacryloyl (GelMA) and (2-(4-vinylphenyl)ethene-1,1,2-triyl)tribenzene (TPEMA)-based multifunctional hydrogel with 3D printability, fluorescence imageability, biodegradability, and biocompatibility is demonstrated. By using 3D direct laser writing method, the hydrogel exhibits its versatility in the customization and fabrication of 3D microstructures. Spherical hydrogel microrobots were fabricated and decorated with magnetic nanoparticles on their surface to render them magnetically responsive, and have demonstrated excellent movement performance and motion controllability. The hydrogel microstructures also represented excellent drug loading/release capacity and degradability by using collagenase, along with stable fluorescence properties. Moreover, cytotoxicity assays showed that the hydrogel was non-toxic, as well as able to support cell attachment and growth, indicating excellent biocompatibility of the hydrogel. The developed multifunctional hydrogel exhibits great potential for biomedical microrobots that are integrated with customizability, 3D printability, motion controllability, drug delivery capacity, fluorescence imageability, degradability, and biocompatibility, thus being able to realize the real in vivo biomedical applications of microrobots.

Genome-wide identification, phylogeny and expression analysis of Hsf gene family in Verbena bonariensis under low-temperature stress.

BACKGROUND: The heat shock transcription factor (Hsf) is a crucial regulator of plant stress resistance, playing a key role in plant stress response, growth, and development regulation. RESULTS: In this study, we utilized bioinformatics tools to screen 25 VbHsf members, which were named VbHsf1-VbHsf25. We used bioinformatics methods to analyze the sequence structure, physicochemical properties, conserved motifs, phylogenetic evolution, chromosome localization, promoter cis-acting elements, collinearity, and gene expression of Hsf heat shock transcription factor family members under low-temperature stress. The results revealed that the majority of the Hsf genes contained motif1, motif2, and motif3, signifying that these three motifs were highly conserved in the Hsf protein sequence of Verbena bonariensis. Although there were some variations in motif deletion among the members, the domain remained highly conserved. The theoretical isoelectric point ranged from 4.17 to 9.71, with 21 members being unstable proteins and the remainder being stable proteins. Subcellular localization predictions indicated that all members were located in the nucleus. Phylogenetic analysis of the Hsf gene family in V. bonariensis and Arabidopsis thaliana revealed that the Hsf gene family of V. bonariensis could be categorized into three groups, with group A comprising 17 members and group C having at least two members. Among the 25 Hsf members, there were 1-3 exons located on seven chromosome fragments, which were unevenly distributed. Collinearity analysis demonstrated the presence of seven pairs of homologous genes in the VbHsf gene family. The Ka/Ks ratios were less than one, indicating that the VbHsf gene underwent purification selection pressure. Additionally, nine genes in V. bonariensis were found to have collinearity with A. thaliana. Promoter analysis revealed that the promoters of all VbHsf genes contained various types of cis-acting elements related to hormones and stress. Based on RNA-seq data, qRT-PCR analysis of six highly expressed genes was performed, and it was found that VbHsf5, VbHsf14, VbHsf17, VbHsf18, VbHsf20 and VbHsf21 genes were highly expressed at 12 h of low-temperature treatment, and the expression decreased after 24 h, among which VbHsf14 was up-regulated at 12 h of low-temperature by 70-fold. CONCLUSIONS: Our study may help reveal the important roles of Hsf in plant development and show insight for the further molecular breeding of V. bonariensis.

peri-Fused polyaromatic molecular contacts for perovskite solar cells.

Molecule-based selective contacts have become a crucial component to ensure high-efficiency inverted perovskite solar cells1-5. These molecules always consist of a conjugated core with heteroatom substitution to render the desirable carrier-transport capability6-9. So far, the design of successful conjugation cores has been limited to two N-substituted π-conjugated structures, carbazole and triphenylamine, with molecular optimization evolving around their derivatives2,5,10-12. However, further improvement of the device longevity has been hampered by the concomitant limitations of the molecular stability induced by such heteroatom-substituted structures13,14. A more robust molecular contact without sacrificing the electronic properties is in urgent demand, but remains a challenge. Here we report a peri-fused polyaromatic core structure without heteroatom substitution that yields superior carrier transport and selectivity over conventional heteroatom-substituted core structures. This core structure produced a relatively chemically inert and structurally rigid molecular contact, which considerably improved the performance of perovskite solar cells in terms of both efficiency and durability. The champion device showed an efficiency up to 26.1% with greatly improved longevity under different accelerated-ageing tests.

Hydrolyzed Chicken Meat Extract and Its Bioactive Cyclopeptides Protect Neural Function by Attenuating Inflammation and Apoptosis via PI3K/AKT and AMPK Pathways.

Cognitive decline is inevitable with age, and due to the lack of well-established pharmacotherapies for neurodegenerative disorders, dietary supplements have become important alternatives to ameliorate brain deterioration. Hydrolyzed chicken meat extract (HCE) and its bioactive components were previously found to improve neuroinflammation and cognitive decline by regulating microglia polarization. However, the effects and mechanisms of these bioactives on neurons remain unclear. Here, the most potent bioactive component on neural function in HCE was screened out, and the detailed mechanism was clarified through in vivo and in vitro experiments. We found that HCE, cyclo(Val-Pro), cyclo(Phe-Phe), cyclo(His-Pro), cyclo(Leu-Lys), and arginine exerted stronger anti-inflammatory and antioxidant effects among the 12 bioactives in amyloid ß (Aß)-treated HT-22 cells. Further transcriptome sequencing and polymerase chain reaction (PCR) array analysis showed that these bioactives participated in different signaling pathways, and cyclo(Val-Pro) was identified as the most potent cyclic dipeptide. In addition, the antiapoptotic and neuroprotective effect of cyclo(Val-Pro) was partly regulated by the activation of PI3K/AKT and AMPK pathways, and the inhibition of these pathways abolished the effect of cyclo(Val-Pro). Moreover, cyclo(Val-Pro) enhanced cognitive function and neurogenesis and alleviated neuroinflammation and oxidative stress in middle-aged mice, with an effect similar to HCE. Hippocampal transcriptome analysis further revealed that HCE and cyclo(Val-Pro) significantly enriched the neuroactive ligand-receptor interaction pathway, verified by enhanced neurotransmitter levels and upregulated neurotransmitter receptor-related gene expression. Therefore, the mechanism of cyclo(Val-Pro) on neural function might be associated with PI3K/AKT and AMPK pathway-mediated antiapoptotic effect and neurogenesis and the activation of the neurotransmitter-receptor pathway.

Identification of novel immune-related signatures for keloid diagnosis and treatment: insights from integrated bulk RNA-seq and scRNA-seq analysis.

BACKGROUND: Keloid is a disease characterized by proliferation of fibrous tissue after the healing of skin tissue, which seriously affects the daily life of patients. However, the clinical treatment of keloids still has limitations, that is, it is not effective in controlling keloids, resulting in a high recurrence rate. Thus, it is urgent to identify new signatures to improve the diagnosis and treatment of keloids. METHOD: Bulk RNA seq and scRNA seq data were downloaded from the GEO database. First, we used WGCNA and MEGENA to co-identify keloid/immune-related DEGs. Subsequently, we used three machine learning algorithms (Randomforest, SVM-RFE, and LASSO) to identify hub immune-related genes of keloid (KHIGs) and investigated the heterogeneous expression of KHIGs during fibroblast subpopulation differentiation using scRNA-seq. Finally, we used HE and Masson staining, quantitative reverse transcription-PCR, western blotting, immunohistochemical, and Immunofluorescent assay to investigate the dysregulated expression and the mechanism of retinoic acid in keloids. RESULTS: In the present study, we identified PTGFR, RBP5, and LIF as KHIGs and validated their diagnostic performance. Subsequently, we constructed a novel artificial neural network molecular diagnostic model based on the transcriptome pattern of KHIGs, which is expected to break through the current dilemma faced by molecular diagnosis of keloids in the clinic. Meanwhile, the constructed IG score can also effectively predict keloid risk, which provides a new strategy for keloid prevention. Additionally, we observed that KHIGs were also heterogeneously expressed in the constructed differentiation trajectories of fibroblast subtypes, which may affect the differentiation of fibroblast subtypes and thus lead to dysregulation of the immune microenvironment in keloids. Finally, we found that retinoic acid may treat or alleviate keloids by inhibiting RBP5 to differentiate pro-inflammatory fibroblasts (PIF) to mesenchymal fibroblasts (MF), which further reduces collagen secretion. CONCLUSION: In summary, the present study provides novel immune signatures (PTGFR, RBP5, and LIF) for keloid diagnosis and treatment, and identifies retinoic acid as potential anti-keloid drugs. More importantly, we provide a new perspective for understanding the interactions between different fibroblast subtypes in keloids and the remodeling of their immune microenvironment.

An assessment of the sensory drivers influencing consumer preference in infant formula, assessed via sensory evaluation and GC-O-MS.

Consumer partiality for food products is related to purchase and consumption behavior, and are influenced by sensory preferences. The sensory and chemical drivers behind consumer preference in the infant formula (IF) were analyzed. A total of 31 aroma-active compounds were identified, playing an important role in the production of off-flavors (especially fishy). Combined with the correlation analysis, the key aroma substances affecting the sensory attributes of IF were initially identified. A21, A22, B9 represented the key substances responsible for producing milky and creamy, while A2, A5, A11, A12, B5, C15, H5 primarily produced fishy. In addition, the two sensory attributes namely milky and creamy, and the T-sweet were more strongly correlated with consumer preference. Therefore, it can be concluded that consumers are more interested in the main flavor of the product than the off-flavor. These findings will inform the quality control of IF and the maintenance of sensory quality.

Case report: Pilomatrix carcinoma with PDL1 expression and CDKN2A aberrant.

Case report: A 55-year-old male patient developed a mass in the left inguinal area with left lower limb swelling and first visited a local hospital 3 months earlier because of unrelieved pain. An MRI scan suggested left suprapubic branch and left acetabular bone destruction, abnormal soft tissue signals within the iliopsoas muscle of the anterior edge of the left iliac bone, and enlarged lymph nodes in the left iliac fossa and left inguinal region. The patient subsequently underwent left pelvic lesion open biopsy and inguinal lymph node resection biopsy. According to pathological reports, the left inguinal mass was considered to be a malignant tumor of cutaneous accessory origin (pilomatrix carcinoma) with extensive vitreous changes. The suprapupubis branch mass was considered to be a bone metastatic pilomatrix carcinoma. Immunohistochemistry (IHC) revealed a PDL1 combined positive score (CPS) of 8. DNA next-generation sequencing (NGS) showed CDKN2A L65Rfs*53 mutation. The patient received three cycles of gemcitabine and nedaplatin. However, the lesion progressed. Conclusion: Chemotherapy is not effective for treating pilomatrix carcinoma. PDL1 antibodies and CDK4/6 inhibitors might be treatment options for pilomatrix carcinoma.

Oculomotor Nerve Palsy Induced by a Cerebral Developmental Venous Anomaly: A Case Report and Comprehensive Review.

BACKGROUND Symptoms caused by developmental venous anomalies (DVAs) are usually mild and unspecific. Despite the benign nature of DVAs, they can occasionally be symptomatic. CASE REPORT A 67-year-old woman presented with sudden diplopia and left eyelid ptosis for 10 days. A neurologic examination revealed left complete oculomotor nerve palsy. Other neurologic deficits, including eye pain or pulsatile tinnitus, were not detected. Furthermore, the visual acuity was normal. Additionally, no retinal hemorrhage, venous dilatation, or fundus tortuosity were observed. No ischemia lesions or neoplasms were observed in MRI, and no widening or enhancement of the cavernous sinus was detected in post-contrast T1-weighted images, but magnetic resonance tomography cerebral angiography (MRTA) detected an offending vessel compressing the left oculomotor nerve in the fossa interpeduncular. We hypothesized that oculomotor nerve palsy (ONP) was caused by an abnormal arterial structure. However, digital subtraction angiography (DSA) revealed no aneurysm or abnormal arterial structure in the arterial phase, while a tortuous and dilated collecting vein was detected in the venous phase, connecting the left temporal lobe to the left cavernous sinus. This indicated a typical caput medusae appearance, suggesting the mechanism of oculomotor palsy caused by compressive impairment of the DVA. The patient refused microvascular decompression surgery, and ONP persisted after 30 days. Management was conservative, with spontaneous resolution at 60 days and no recurrence during the 2-year follow-up. CONCLUSIONS ONP is rarely caused by DVAs, which are easily ignored due to their benign nature. Cerebral vein examinations are advised for patients exhibiting clinical symptoms of unknown etiology.

Application and progress of new technologies and new materials in the treatment of pathological scar.

Pathological scars (PS), including hypertrophic scars (HTS) and keloids, are a common complication of poor wound healing that significantly affects patients' quality of life. Currently, there are several treatment options for PS, including surgery, drug therapy, radiation therapy, and biological therapy. However, these treatments still face major challenges such as low efficacy, high side effects, and a high risk of recurrence. Therefore, the search for safer and more effective treatments is particularly urgent. New materials often have less immune rejection, good histocompatibility, and can reduce secondary damage during treatment. New technology can also reduce the side effects of traditional treatments and the recurrence rate after treatment. Furthermore, derivative products of new materials and biomaterials can improve the therapeutic effect of new technologies on PS. Therefore, new technologies and innovative materials are considered better options for enhancing PS. This review concentrates on the use of two emerging technologies, microneedle (MN) and photodynamic therapy (PDT), and two novel materials, photosensitizers and exosomes (Exos), in the treatment of PS.

Increased regional body fat is associated with depressive symptoms: a cross-sectional analysis of NHANES data obtained during 2011-2018.

AIMS: The findings from previous epidemiological studies of the association between regional body fat and depressive symptoms have been unclear. We aimed to determine the association between the body fat in different regions and depressive symptoms based on data from the National Health and Nutrition Examination Survey (NHANES). METHODS: This study included 3393 participants aged ≥ 20 years from the NHANES performed during 2011-2018. Depressive symptoms were assessed using the Patient Health Questionnaire-9. The fat mass (FM) was measured in different regions using dual-energy X-ray absorptiometry to determine the total FM, trunk FM, arm FM, and leg FM. The FM index (FMI) was obtained by dividing the FM in kilograms by the square of the body height in meters. Weighted data were calculated in accordance with analytical guidelines. Linear logistic regression models were used to quantify the association between regional FMI and depressive symptoms. Univariate and stratified analyses were also performed. RESULTS: The participants in this study comprised 2066 males and 1327 females. There were 404 (11.91%) participants with depressive symptoms, who were aged 40.89 ± 11.74 years and had a body mass index of 30.07 ± 7.82 kg/m². A significant association was found between total FMI and depressive symptoms. In the fully adjusted multivariate regression model, a higher total FMI (odds ratio = 2.18, 95% confidence interval [CI] = 1.08-4.39) was related to a higher risk of depressive symptoms, while increased total FMI (ß = 1.55, 95% CI = 0.65-2.44, p = 0.001), trunk FMI (ß = 0.57, 95% CI = 0.04-1.10, p = 0.036), and arm FMI (ß = 0.96, 95% CI = 0.33-1.59, p = 0.004) were significantly associated with PHQ-9 (Patient Health Questionnaire-9) scores, whereas the leg FMI was not (p = 0.102). The weighted association between total FMI and depressive symptoms did not differ significantly between most of the subpopulations (all p values for interaction > 0.05). The risk of having depression was higher in individuals who were non-Hispanic Whites, smokers, drinkers, obese, and had diabetes and thyroid problems (p < 0.05). CONCLUSION: These findings suggest that the population with a higher regional FMI is more likely to have depressive symptoms, especially in those who also have an increased total FMI. The association is more pronounced in individuals who are smokers, drinkers, obese, and have diabetes and thyroid problems.

The impact and inflammatory characteristics of SARS-CoV-2 infection during ovarian stimulation on the outcomes of assisted reproductive treatment.

Introduction: Despite the global prevalence of coronavirus disease 2019 (COVID-19), limited research has been conducted on the effects of SARS-CoV-2 infection on human reproduction. The aims of this study were to investigate the impact of SARS-CoV-2 infection during controlled ovarian stimulation (COS) on the outcomes of assisted reproductive treatment (ART) and the cytokine status of patients. Methods: This retrospective cohort study included 202 couples who received ART treatment, 101 couples infected with SARS-CoV-2 during COS and 101 matched uninfected couples. The parameters of ovarian stimulation and pregnancy outcomes were compared between the two groups. The All-Human Inflammation Array Q3 kit was utilized to measure cytokine levels in both blood and follicular fluid. Results: No difference was found in the number of good-quality embryos (3.3 ± 3.1 vs. 3.0 ± 2.2, P = 0.553) between the infected and uninfected groups. Among couples who received fresh embryo transfers, no difference was observed in clinical pregnancy rate (53.3% vs. 51.5%, P = 0.907). The rates of fertilization, implantation, miscarriage, ectopic pregnancy and live birth were also comparable between the two groups. After adjustments were made for confounders, regression models indicated that the quality of embryos (B = 0.16, P = 0.605) and clinical pregnancy rate (P = 0.206) remained unaffected by SARS-CoV-2 infection. The serum levels of MCP-1, TIMP-1, I-309, TNF-RI and TNF-RII were increased, while that of eotaxin-2 was decreased in COVID-19 patients. No significant difference was found in the levels of cytokines in follicular fluid between the two groups. Conclusion: Asymptomatic or mild COVID-19 during COS had no adverse effects on ART outcomes. Although mild inflammation was present in the serum, it was not detected in the follicular fluid of these patients. The subsequent immune response needs further investigation.

Sustained attention operates via dissociable neural mechanisms across different eccentric locations.

In primates, foveal and peripheral vision have distinct neural architectures and functions. However, it has been debated if selective attention operates via the same or different neural mechanisms across eccentricities. We tested these alternative accounts by examining the effects of selective attention on the steady-state visually evoked potential (SSVEP) and the fronto-parietal signal measured via EEG from human subjects performing a sustained visuospatial attention task. With a negligible level of eye movements, both SSVEP and SND exhibited the heterogeneous patterns of attentional modulations across eccentricities. Specifically, the attentional modulations of these signals peaked at the parafoveal locations and such modulations wore off as visual stimuli appeared closer to the fovea or further away towards the periphery. However, with a relatively higher level of eye movements, the heterogeneous patterns of attentional modulations of these neural signals were less robust. These data demonstrate that the top-down influence of covert visuospatial attention on early sensory processing in human cortex depends on eccentricity and the level of saccadic responses. Taken together, the results suggest that sustained visuospatial attention operates differently across different eccentric locations, providing new understanding of how attention augments sensory representations regardless of where the attended stimulus appears.

Circadian tumor infiltration and function of CD8+ T cells dictate immunotherapy efficacy.

The quality and quantity of tumor-infiltrating lymphocytes, particularly CD8+ T cells, are important parameters for the control of tumor growth and response to immunotherapy. Here, we show in murine and human cancers that these parameters exhibit circadian oscillations, driven by both the endogenous circadian clock of leukocytes and rhythmic leukocyte infiltration, which depends on the circadian clock of endothelial cells in the tumor microenvironment. To harness these rhythms therapeutically, we demonstrate that efficacy of chimeric antigen receptor T cell therapy and immune checkpoint blockade can be improved by adjusting the time of treatment during the day. Furthermore, time-of-day-dependent T cell signatures in murine tumor models predict overall survival in patients with melanoma and correlate with response to anti-PD-1 therapy. Our data demonstrate the functional significance of circadian dynamics in the tumor microenvironment and suggest the importance of leveraging these features for improving future clinical trial design and patient care.

Selective haematological cancer eradication with preserved haematopoiesis.

Haematopoietic stem cell (HSC) transplantation (HSCT) is the only curative treatment for a broad range of haematological malignancies, but the standard of care relies on untargeted chemotherapies and limited possibilities to treat malignant cells after HSCT without affecting the transplanted healthy cells1. Antigen-specific cell-depleting therapies hold the promise of much more targeted elimination of diseased cells, as witnessed in the past decade by the revolution of clinical practice for B cell malignancies2. However, target selection is complex and limited to antigens expressed on subsets of haematopoietic cells, resulting in a fragmented therapy landscape with high development costs2-5. Here we demonstrate that an antibody-drug conjugate (ADC) targeting the pan-haematopoietic marker CD45 enables the antigen-specific depletion of the entire haematopoietic system, including HSCs. Pairing this ADC with the transplantation of human HSCs engineered to be shielded from the CD45-targeting ADC enables the selective eradication of leukaemic cells with preserved haematopoiesis. The combination of CD45-targeting ADCs and engineered HSCs creates an almost universal strategy to replace a diseased haematopoietic system, irrespective of disease aetiology or originating cell type. We propose that this approach could have broad implications beyond haematological malignancies.