An In Vitro Macrophage Response Study of Silk Fibroin and Silk Fibroin/Nano-Hydroxyapatite Scaffolds for Tissue Regeneration Application.

In recent years, silk fibroin (SF) has been incorporated with low crystallinity nanohydroxyapatite (nHA) as a scaffold for various tissue regeneration applications due to the mechanical strength of SF and osteoconductive properties of nHA. However, currently, there is a lack of understanding of the immune response toward the degradation products of SF with nHA composite after implantation. It is known that particulate fragments from the degradation of a biomaterial can trigger an immune response. As the scaffold is made of degradable materials, the degradation products may contribute to the inflammation. Therefore, in this study, the effects of the enzymatic degradation of the SF/nHA scaffold on macrophage response were investigated in comparison to the control SF scaffold. Since the degradation products of a scaffold can influence macrophage polarization, it can be hypothesized that as the SF and SF/nHA scaffolds were degraded in vitro using protease XIV solution, the degradation products can contribute to the polarization of THP-1-derived macrophages from pro-inflammatory M1 to anti-inflammatory M2 phenotype. The results demonstrated that the initial (day 1) degradation products of the SF/nHA scaffold elicited a pro-inflammatory response, while the latter (day 24) degradation products of the SF/nHA scaffold elicited an anti-inflammatory response. Moreover, the degradation products from the SF scaffold elicited a higher anti-inflammatory response due to the faster degradation of the SF scaffold and a higher amino acid concentration in the degradation solution. Hence, this paper can help elucidate the contributory effects of the degradation products of SF and SF/nHA scaffolds on macrophage response and provide greater insights into designing silk-based biomaterials with tunable degradation rates that can modulate macrophage response for future tissue regeneration applications.

Incidence and risk factors of antidepressant withdrawal symptoms: a meta-analysis and systematic review.

Antidepressants are among the most extensively prescribed psychotropic drugs worldwide. Discontinuation induced withdrawal symptoms have been reported for almost all antidepressants. The incidence of antidepressant withdrawal syndrome (AWS) and other characteristics remain unknown. We searched the PubMed, Embase, PsycINFO, MEDLINE, CINAHL, and Cochrane Central Register of Controlled Trials databases from inception to December 31, 2023. Randomized double-blinded trials, longitudinal or cross-sectional studies that reported the incidence and other characteristics of antidepressant withdrawal symptoms were included. The pooled incidence of AWS was calculated by a random effects model. We included 35 studies, of which 2 studies just provided incidence of specific withdrawal symptoms, and 4 studies only described other characteristics. The pooled incidence of AWS from all available studies was 42.9%, from 11 RCTs was 44.4%, in studies in which the treatment duration was mostly 8-12 weeks, which usually appear within 2 weeks, and were generally measured for <4 weeks. The incidence in selective serotonin-norepinephrine reuptake inhibitors was the lowest (29.7%), followed by selective serotonin reuptake inhibitors (45.6%) and tricyclic antidepressants (59.7%), without significant differences (p = 0.221). Treatment duration showed a dose-response to the incidence of AWS (6-12 W: 35.1%, 12-24 W: 42.7%, >24 W: 51.4%). The half-life did not show such a simple dose-dependent relationship. The pooled estimate was robust regardless whether withdrawal symptoms were measured in RCTs or observational studies (including face-to-face and online survey studies). Tapering the dose reduced the incidence of AWS compared with abrupt stoppage (34.5% vs 42.5%), without a significant difference (p = 0.484). Risk factors for withdrawal symptoms included being female, younger, experiencing adverse effects early in treatment, taking higher doses or longer duration of medication, abrupt cessation of drugs, and those with a lower clearance of drugs or with serotonin 1A receptor gene variation. The findings suggest the incidence of AWS are common and some clinical characteristics and risk factors which can help clinicians identify who is at greater risk of experiencing AWS. Discontinuation studies on long-term antidepressant users with long follow-up periods are required in the future.

Unraveling the causative connection between urticaria, inflammatory cytokines, and mental disorders: Perspectives from genetic evidence.

BACKGROUND: The genetic association between urticaria and mental disorders and whether inflammatory cytokines mediate this process remains unclear. MATERIALS AND METHODS: A Mendelian randomization (MR) approaches to elucidate the causal relationship between urticaria and mental disorders and to validate the mediation of inflammatory cytokines. Genome-wide association study (GWAS) databases used were obtained from Psychiatric Genomics Cooperation (PGC), GWAS Catalog, and FinnGen Consortium. Our study was conducted using inverse variance weighted (IVW) and Bayesian weighted MR (BWMR) methods for joint analysis. RESULTS: The MR results showed that urticaria increased the risk of attention deficit hyperactivity disorder (ADHD) (odds ratio [OR] = $ = $ 1.088, 95% confidence interval [CI]: 1.026-1.154, p = $ = $ 0.0051); cholinergic urticaria increased the risk of bipolar disorder (BD) (OR = $ = $ 1.012, 95% CI: 1.001-1.022, p = $ = $ 0.0274); dermatographic urticaria increased the risk of ADHD (OR = $ = $ 1.057, 95% CI: 1.005-1.112, p = $ = $ 0.0323); idiopathic urticaria increased the risk of schizophrenia (SCZ) (OR = $ = $ 1.057, 95% CI: 1.005-1.112, p = $ = $ 0.0323); other unspecified urticaria increased the risk of ADHD (OR = $ = $ 1.085, 95% CI: 1.023-1.151, p = $ = $ 0.0063). We found that eight inflammatory cytokines were negatively associated with mental disorders and seven inflammatory cytokines were positively associated with mental disorders. Finally, our results suggested that inflammatory cytokines do not act as mediators between urticaria and mental disorders. CONCLUSIONS: Our study reveals a causal relationship between urticaria and the increased risk of mental disorders. We suggest that the treatment of urticaria could incorporate psychiatric interventions and mental health assessment of patients.

Variation in immunoglobulin use and impact on survival in myeloma.

Serious infection is common in patients with multiple myeloma due to immune deficiency from the underlying disease and/or its treatment. Immunoglobulin replacement is one approach to reduce infection risk in these patients. However, few real-world data exist on its use in patients with myeloma. We investigated immunoglobulin use in Australia, New Zealand and Asia-Pacific using registry data and explored its association with survival outcomes. A total of 2374 patients with a median follow-up time of 29.5 months (interquartile range 13.3-54.3 months) were included in the analysis - 1673 from Australia, 313 Korea, 281 New Zealand and 107 Singapore. Overall, 7.1% of participants received immunoglobulin replacement within 24 months of diagnosis. Patients who received immunoglobulin replacement were likely to be younger, had lower baseline IgG levels (excluding paraprotein), were more likely to have baseline hypogammaglobulinaemia, baseline severe hypogammaglobulinaemia and abnormal baseline fluorescent in-situ hybridisation status, receive first-line myeloma treatment with immunomodulatory drugs or anti-CD38 therapy and undergo upfront autologous stem cell transplant. In our patient cohort, the use of immunoglobulin was not associated with overall survival benefit at the time of last follow-up (adjusted hazard ratio 0.72, 95% CI 0.46-1.14, p = 0.16). Understanding treatment approaches in clinical practice can help support future planning and provision of immunoglobulin resources.

Dynamic regulation of phosphorylation of NMDA receptor GluN2B subunit tyrosine residues mediates ketamine rapid antidepressant effects.

The rapid antidepressant effects of ketamine depend on the N-methyl-D-aspartate (NMDA) receptor containing 2B subunit (NR2B), whose function is influenced by its phosphorylated regulation and distribution within and outside synapses. It remains unclear if ketamine's rapid onset of antidepressant effects relies on the dynamic phosphorylated regulation of NR2B within and outside synapses. Here, we show that ketamine rapidlyalleviated depression-like behaviors and normalized abnormal expression of pTyr1472NR2B and striatal-enriched protein tyrosine phosphatase (STEP) 61 within and outside synapses in the medial prefrontal cortex (mPFC) induced by chronic unpredictable stress (CUS) and conditional knockdown of STEP 61, a key phosphatase of NR2B, within 1 hour after administration Together, our results delineate the rapid initiation of ketamine's antidepressant effects results from the restoration of NR2B phosphorylation homeostasis within and outside synapses. The dynamic regulation of phosphorylation of NR2B provides a new perspective for developing new antidepressant strategies.

The ldp1 Mutation Affects the Expression of Auxin-Related Genes and Enhances SAM Size in Rice.

Panicle type is one of the important factors affecting rice (Oryza sativa L.) yield, and the identification of regulatory genes in panicle development can provide significant insights into the molecular network involved. This study identified a large and dense panicle 1 (ldp1) mutant produced from the Wuyunjing 7 (WYJ7) genotype, which displayed significant relative increases in panicle length, number of primary and secondary branches, number of grains per panicle, grain width, and grain yield per plant. Scanning electron microscopy results showed that the shoot apical meristem (SAM) of ldp1 was relatively larger at the bract stage (BM), with a significantly increased number of primary (PBM) and secondary branch (SBM) meristematic centers, indicating that the ldp1 mutation affects early stages in SAM development Comparative RNA-Seq analysis of meristem tissues from WYJ7 and ldp1 at the BM, PBM, and SBM developmental stages indicated that the number of differentially expressed genes (DEGs) were highest (1407) during the BM stage. Weighted gene coexpression network analysis (WGCNA) revealed that genes in one module (turquoise) are associated with the ldp1 phenotype and highly expressed during the BM stage, suggesting their roles in the identity transition and branch differentiation stages of rice inflorescences. Hub genes involved in auxin synthesis and transport pathways, such as OsAUX1, OsAUX4, and OsSAUR25, were identified. Moreover, GO and KEGG analysis of the DEGs in the turquoise module and the 1407 DEGs in the BM stage revealed that a majority of genes involved in tryptophan metabolism and auxin signaling pathway were differentially expressed between WYJ and ldp1. The genetic analysis indicated that the ldp1 phenotype is controlled by a recessive monogene (LDP1), which was mapped to a region between 16.9 and 18.1 Mb on chromosome seven. This study suggests that the ldp1 mutation may affect the expression of key genes in auxin synthesis and signal transduction, enhance the size of SAM, and thus affect panicle development. This study provides insights into the molecular regulatory network underlying rice panicle morphogenesis and lays an important foundation for further understanding the function and molecular mechanism of LDP1 during panicle development.

Organic Fluorophores with Large Stokes Shift for the Visualization of Rapid Protein and Nucleic Acid Assays.

Organic small-molecule fluorophores, characterized by flexible chemical structure and adjustable optical performance, have shown tremendous potential in biosensing. However, classical organic fluorophore motifs feature large overlap between excitation and emission spectra, leading to the requirement of advanced optical set up to filter desired signal, which limits their application in scenarios with simple settings. Here, a series of wavelength-tunable small-molecule fluorescent dyes (PTs) bearing simple organic moieties have been developed, which exhibit Stokes shift up to 262 nm, molar extinction coefficients ranged 30,000-100,000 M-1 cm-1, with quantum yields up to 54.8 %. Furthermore, these dyes were formulated into fluorescent nanoparticles (PT-NPs), and applied in lateral flow assay (LFA). Consequently, limit of detection for SARS-CoV-2 nucleocapsid protein reached 20 fM with naked eye, a 100-fold improvement in sensitivity compared to the pM detection level for colloidal gold-based LFA. Besides, combined with loop-mediated isothermal amplification (LAMP), the LFA system achieved the visualization of single copy level nucleic acid detection for monkeypox (Mpox).

ATG14 targets lipid droplets and acts as an autophagic receptor for syntaxin18-regulated lipid droplet turnover.

Lipid droplets (LDs) are dynamic lipid storage organelles that can be degraded by autophagy machinery to release neutral lipids, a process called lipophagy. However, specific receptors and regulation mechanisms for lipophagy remain largely unknown. Here, we identify that ATG14, the core unit of the PI3KC3-C1 complex, also targets LD and acts as an autophagic receptor that facilitates LD degradation. A negative regulator, Syntaxin18 (STX18) binds ATG14, disrupting the ATG14-ATG8 family members interactions and subverting the PI3KC3-C1 complex formation. Knockdown of STX18 activates lipophagy dependent on ATG14 not only as the core unit of PI3KC3-C1 complex but also as the autophagic receptor, resulting in the degradation of LD-associated anti-viral protein Viperin. Furthermore, coronavirus M protein binds STX18 and subverts the STX18-ATG14 interaction to induce lipophagy and degrade Viperin, facilitating virus production. Altogether, our data provide a previously undescribed mechanism for additional roles of ATG14 in lipid metabolism and virus production.

MPSketch: Message Passing Networks via Randomized Hashing for Efficient Attributed Network Embedding.

Given a network, it is well recognized that attributed network embedding represents each node of the network in a low-dimensional space, and, thus, brings considerable benefits for numerous graph mining tasks. In practice, a diverse set of graph tasks can be processed efficiently via the compact representation that preserves content and structure information. The majority of attributed network embedding approaches, especially, the graph neural network (GNN) algorithms, are substantially costly in either time or space due to the expensive learning process, while the randomized hashing technique, locality-sensitive hashing (LSH), which does not need learning, can speedup the embedding process at the expense of losing some accuracy. In this article, we propose the MPSketch model, which bridges the performance gap between the GNN framework and the LSH framework by adopting the LSH technique to pass messages and capture high-order proximity in a larger aggregated information pool from the neighborhood. The extensive experimental results confirm that in node classification and link prediction, the proposed MPSketch algorithm enjoys performance comparable to the state-of-the-art learning-based algorithms and outperforms the existing LSH algorithms, while running faster than the GNN algorithms by 3-4 orders of magnitude. More precisely, MPSketch runs 2121, 1167, and 1155 times faster than GraphSAGE, GraphZoom, and FATNet on average, respectively.

High-throughput analysis of glycan sorting into extracellular vesicles.

Extracellular vesicles (EVs) are cell-released vesicles that mediate intercellular communication by transferring bioactive cargo. Protein and RNA sorting into EVs has been extensively assessed, while selective enrichment of glycans in EVs remains less explored. In this study, a mass spectrometry-based approach, glycan node analysis (GNA), was applied to broadly assess the sorting of glycan features into EVs. Two metastatic variants (lung and bone) generated in mouse modes from the MDA-MB-231 human breast cancer cell line were assessed, as these EVs are known to contain distinct organotropic biomolecules. EVs were isolated from conditioned cell culture medium by tangential flow filtration and authenticated by standard techniques. GNA analysis revealed selective enrichment of several glycan features in EVs compared to the originating cells, particularly those associated with binding to the extracellular matrix, which was also observed in EVs from the parental MDA-MB-231 cell line (human pleural metastases). The bone-tropic variant displayed enrichment of distinct EV glycan features compared to the lung-tropic one. Additionally, the metastatic variants generated in mouse models displayed reduced EV glycan sorting compared to the parental metastatic cell line. This study represents the first comprehensive assessment of differences in glycan features between EVs and originating cells and provides evidence that the diversity of EV glycan sorting is reduced upon generation of variant cell lines in mouse models. Future research is likely to uncover novel mechanisms of EV glycan sorting, shed light on glycan features for EV authentication or biomarker purposes, and assess functional roles of the EV glycocode in (patho)physiology.

Phytochelatin-Mediated Cultivar-Dependent Cd Accumulations of Lactuca sativa and Implication for Cd Pollution-Safe Cultivars Screening.

Cd pollution-safe cultivar (Cd-PSC) is a feasible strategy to minimize Cd contamination in leafy vegetables. The shoot Cd concentrations of 23 Lactuca sativa cultivars under Cd stress ranged from 0.124 to 2.155 mg·kg-1 with a maximum cultivar difference of 8 folds. Typical Cd-PSC C16 (L) and high-Cd-accumulating cultivar C13 (H) were screened to investigate the mechanisms of Cd accumulations in L. sativa through determining Cd concentrations, Cd subcellular distributions, phytochelatin profiles, and phytochelatin biosynthesis-related genes' expressions. Higher Cd distribution in a heat stable fraction in C13 (H) indicated that the high Cd accumulation trait of C13 (H) mainly depended on the Cd-phytochelatin complexes. Root phytochelatin concentrations were significantly elevated in C13 (H) (5.83 folds) than in C16 (L) (2.69 folds) (p < 0.05) under Cd stress. Significantly downregulated expressions of glutathione S-transferase rather than the regulation of phytochelatin synthesis genes in the root of C13 (H) might be responsible for sufficient glutathione supply for phytochelatins synthesis. These findings suggested that phytochelatin elevation in C13 (H) would favor the Cd root to shoot transportation, which provides new insights into the phytochelatin-related cultivar-dependent Cd accumulating characteristic in L. sativa.

Effectiveness and safety of second-generation antipsychotics for psychiatric disorders apart from schizophrenia: A systematic review and meta-analysis.

Second-generation antipsychotics (SGAs) are widely used in treating schizophrenia and related disorders, also other mental disorders. However, the efficacy and safety of SGAs for treating other mental disorders is unclear. A systematic literature search for randomized, placebo-controlled trials of 11 SGAs for treating 18 mental disorders apart from schizophrenia were carried out from database inception to April 3, 2022. The primary outcome was the mean change in the total score for different mental disorders. The secondary outcome was the odds ratio (OR) of response, remission rates and risk ratio (RR) of adverse events (AEs). A total of 181 studies (N = 65,480) were included. All SGAs showed significant effects in treating other mental disorders compared with placebo, except autistic disorder and dementia. Aripiprazole is the most effective treatment for bipolar mania [effect size = -0.90, 95% CI: -1.59, -0.21] and Tourette's disorder [effect size = -0.80, 95% CI: -1.14, -0.45], olanzapine for bipolar depression [effect size = -0.86, 95% CI: -1.32, -0.39] and post-traumatic stress disorder [effect size = -0.98, 95% CI: -1.55, -0.41], lurasidone for depression [effect size = -0.66, 95% CI: -0.82, -0.50], quetiapine for anxiety [effect size = -1.20, 95% CI: -1.96, -0.43], sleep disorders [effect size = -1.2, 95% CI: -1.97, -0.58], and delirium [effect size = -0.36, 95% CI: -0.70, -0.03], and risperidone for obsessive-compulsive disorder [effect size = -2.37, 95% CI: -3.25, -1.49], respectively. For safety, AE items for each SGAs was different. Interestingly, we found that some AEs of OLZ, QTP, RIS and PALI have significant palliative effects on some symptoms. Significant differences in the efficacy and safety of different SGAs for treatment of other mental disorders should be considered for choosing the drug and for the balance between efficacy and tolerability for the specific patient.

Association between serum uric acid/high-density lipoprotein cholesterol ratio and hypertension among reproductive-aged women.

BACKGROUND: Uric acid/high-density lipoprotein cholesterol ratio (UHR) is a novel index of inflammation and metabolism that has been investigated in various diseases. However, association between UHR and hypertension among reproductive-aged women is unclear. METHODS: In this cross-sectional study, we investigated the association between serum UHR and hypertension among 5485 women aged 20-44 years based on the National Health and Nutrition Examination Survey (NHANES) database using various methods, including univariate and multivariate logistic regression analysis, stratified analysis, and spline regression. P < 0.05 was considered statistically significant. RESULTS: There was significant difference in UHR between the women with and without hypertension (P < 0.001). After adjusting for several covariates, UHR was positively correlated with hypertension (OR > 1, P < 0.001). In the subgroup analysis, the positive correlations still remained between UHR and hypertension in women with various age and those with BMI ≥ 30 kg/m2 (P < 0.05) excepted for adjusting for all covariates. We further found an inflection point of the threshold effect for UHR, and the prevalence of hypertension showed different increased trends below and above the threshold. CONCLUSION: This study indicated a positive association between serum UHR and hypertension among reproductive-aged women, indicating that UHR is a potential clinical marker of hypertension in women.

Hyaluronic acid: An overlooked extracellular vesicle contaminant.

The variable presence of contaminants in extracellular vesicle (EV) samples is one of the major contributors to a lack of inter-study reproducibility in the field. Well-known contaminants include protein aggregates, RNA-protein complexes and lipoproteins, which resemble EVs in shape, size and/or density. On the contrary, polysaccharides, such as hyaluronic acid (HA), have been overlooked as EV contaminants. Here, it is shown that low and medium molecular weight HA polymers are unexpectedly retained to some extent in EV fractions using two common isolation methods known for high purity: size-exclusion chromatography and tangential flow filtration. Although these isolation techniques are capable of efficient removal of non-EV-associated proteins, this is not the case for HA polymers, which are partially retained in a molecular weight-dependent manner, especially with size-exclusion chromatography. The supramolecular structure and hydrodynamic size of HA are likely to contribute to isolation in EV fractions of filtration-based approaches. Conversely, HA polymers were not retained with ultracentrifugation and polymer-based precipitation methods, which are known for co-isolating other types of contaminants. HA has a broad range of immunomodulatory effects, similar to those ascribed to various sources of EVs. Therefore, HA contaminants should be considered in future studies to avoid potential inaccurate attributions of functional effects to EVs.

Developing mango powders by foam mat drying technology.

Using mango purée from overripe mangoes to produce powders helped to solve agricultural product stagnation. The research investigates the effect of thickening additives, convection drying, and heat pump drying on bioactive compounds such as total phenolic content (TPC), total flavonoid content (TFC), color, and solubility of the final product. The obtained results showed that the mixture (gum arabic and maltodextrin in the ratio 50:50 w/w) at a concentration of 15% gave a good quality powder texture when dried by hot air convection at 55°C with TPC (21.24 ± 1.58 mg GAE/g dry weight [DW]) and TFC (0.34 ± 0.02 mg QE/g DW), respectively. In addition, the product has a high solubility of 64.35%, with the highest pass-through point of 17.11.

Assessing the impact of health information exchange on hospital data breach risk.

OBJECTIVE: Widespread electronic health information exchange (HIE) across hospitals remains an important policy goal for reducing costs and improving the quality of care. Meanwhile, cybersecurity incidents are a growing threat to hospitals. The relationship between the electronic sharing of health information and cybersecurity incidents is not well understood. The objective of this study was to empirically examine the impact of hospitals' HIE engagement on their data breach risk. MATERIALS AND METHODS: A balanced panel dataset included 4,936 US community hospitals spanning the period 2010-2017, which was assembled by linking the American Hospital Association annual survey database and the Information Technology (IT) supplement, and the Department of Health and Human Services reports of health data breaches. The relationship between HIE engagement and hospital data breaches was modeled using a difference-in-differences specification controlling for time-varying hospital characteristics. RESULTS: The percentage of hospitals electronically exchanging information has more than tripled (from 18% to 68%) from 2010 to 2017. Hospital data breaches increased concurrently, largely due to the rise in hacking and unauthorized access. HIE engagement was associated with a 0.672 percentage point increase in the probability of an IT breach three years after the engagement. Hospitals actively engaging in a health information organization and exchanging data with outside providers were associated with a higher risk of IT related breaches in the long run; however, hospitals actively engaging in HIE and exchanging data with inside providers were not associated with any significant risk of IT related breaches. DISCUSSION: Over time, the increasing amount and complexity of patient information being exchanged can create challenges for cybersecurity if data protection is not up to date. Additionally, data security depends on the weakest link of HIE, and providers with fewer resources for data governance and infrastructure are more vulnerable to data breaches. CONCLUSION: Moving toward widespread health information exchange has important cybersecurity implications that can significantly impact both patients and healthcare organizations.

SIRIUS, Ultra-Scintillating Upconversion Breast Implant for Remote Orthotopic Photodynamic Therapy.

Present day strategies for delivery of wireless photodynamic therapy (PDT) to deep-seated targets are limited by the inadequacy of irradiance and insufficient therapeutic depth. Here we report the design and preclinical validation of a flexible wireless upconversion nanoparticle (UCNP) implant (SIRIUS) that is capable of large field, high intensity illumination for PDT of deep-seated tumors. The implant achieves this by incorporating submicrometer core-shell-shell NaYF4 UCNPs into its design, which significantly enhances upconversion efficiency and mitigates light loss from surface quenching. We demonstrate the efficacy of SIRIUS UCNP implant mediated PDT in preclinical breast cancer disease models. In our in vitro experiments, SIRIUS directed 5-Aminolevulinic Acid (5-ALA) based wireless PDT leads to significant reactive oxygen species (ROS) generation and tumor apoptosis in hormonal receptor+/HER2+ (MCF7) and triple-negative (MDA-MB-231) breast cancer cell lines. In our in vivo rodent model, SIRIUS-driven PDT is shown to be significant in regressing tumors when applied to orthotopically inoculated breast tumors. Following successful preclinical validation, we also describe a clinical prototype of UCNP breast implant with potential dual cosmetic and onco-therapeutic functions. SIRIUS is an upconversion breast implant for wireless PDT that fulfils all the design prerequisites necessary for seamless clinical translation.

Association between thyroid autoimmunity and clinical characteristics in first-episode and drug-naive depressed patients with suicide attempts.

BACKGROUND: Previous reports had linked depression to thyroid function. However, the relationship between thyroid function and clinical characteristics in major depressive disorder (MDD) patients with suicidal attempts (SA) is still unclear. AIMS: This study aims to reveal the association between thyroid autoimmunity and clinical characteristics in depressed patients with SA. METHODS: We divided 1718 first-episode and drug-naive MDD patients into groups with suicide attempt (MDD-SA) and without suicide attempt (MDD-NSA). Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), and the positive subscale of the Positive and Negative Syndrome Scale (PANSS) were assessed; thyroid function and autoantibodies were detected. RESULTS: The total scores of HAMD, HAMA and psychotic positive symptoms were significantly higher in patients with MDD-SA, accompanied by higher levels of TSH, TG-Ab and TPO-Ab, than in patients with MDD-NSA, without gender differences. Total scores of positive symptoms (TSPS) in MDD-SA patients with increased TSH or TG-Ab was significantly higher than in MDD-NSA patients and in MDD-SA patients with normal TSH and TG-Ab. The proportion of elevated-TSPS in MDD-SA patients was >4 times that in MDD-NSA patients. The proportion of MDD-SA patients with elevated-TSPS was >3 times that with not-elevated TSPS patients. CONCLUSIONS: Thyroid autoimmune abnormalities and psychotic positive symptoms may be the clinical features of MDD-SA patients. Psychiatrists should be more alert to the possibility of suicidal behaviors when they first encounter such a patient.

The effect of chondroitin sulfate concentration and matrix stiffness on chondrogenic differentiation of mesenchymal stem cells.

Chondroitin sulfate (CS), a glycosaminoglycan of native cartilage, has shown its potential in promoting chondrogenesis of mesenchymal stem cells (MSCs), whereas the effect of matrix stiffness in a CS-containing 3D environment on chondrogenesis is still poorly understood. Herein, this study aimed at assessing the effect of CS concentration and stiffness of CS-containing hydrogels on the chondrogenesis of MSCs. Hydrogels composed of 6% (w/v) gelatin methacryloyl (GelMA) and three concentrations, i.e., 4%, 6%, or 10% (w/v), of methacrylated chondroitin sulfate (CSMA) were prepared. The hydrogels of each composition were prepared with two stiffness values (33.36 ± 8.25 kPa vs. 8.42 ± 2.83 kPa). Physical characterization showed similar microporous structures among the six groups, higher swelling ratios and faster degradation in the soft hydrogel groups. MSCs were encapsulated in the six groups of hydrogels and they underwent 28-day chondrogenic differentiation. The cell viability in each group on day 1 was similar and most cells exhibited a round shape without spreading. Afterwards, cellular protrusions in soft hydrogels remained filopodium-like from day 14 to day 28, while most protrusions were lamellipodium-like in stiff hydrogels on day 14 and then transformed into a spherical shape on day 28. The expression of chondrogenic markers analysed by real-time qPCR and immunohistochemical staining demonstrated that the optimal CS concentration for chondrogenesis was 6% (w/v) regardless of the stiffness of hydrogels. In addition, with the same CSMA concentration, the trend was observed that the stiff hydrogels supported superior chondrogenesis of MSCs compared to the soft hydrogel. To summarize, this study presents an advancement in the optimization of CSMA concentration and stiffness of hydrogels for chondrogenesis. In the CSMA/GelMA hydrogel, 6% (w/v) CSMA with an initial Young's modulus around 33 kPa was recommended for cartilage tissue engineering.