Mechanical shear flow regulates the malignancy of colorectal cancer cells.

Colorectal cancer (CRC) is notable for its high mortality and high metastatic characteristics. The shear force generated by bloodstream provides mechanical signals regulating multiple responses of cells, including metastatic cancer cells, dispersing in blood vessels. We, therefore, studied the effect of shear flow on circulating CRC cells in the present study. The CRC cell line SW620 was subjected to shear flow of 12.5 dynes/cm2 for 1 and 2 h separately. Resulting elevated caspase-9 and -3 indicated that shear flow initiated the apoptosis of SW620. Enlarged cell size associated with a higher level of cyclin D1 was coincident with the flow cytometric results indicating that the cell cycle was arrested at the G1 phase. An elevated phosphor-eNOSS1177 increased the production of nitric oxide and led to reactive oxygen species-mediated oxidative stress. Shear flow also regulated epithelial-mesenchymal transition (EMT) by increasing E-cadherin and ZO-1 while decreasing Snail and Twist1. The migration and invasion of sheared SW620 were also substantially decreased. Further investigations showed that mitochondrial membrane potential was significantly decreased, whereas mitochondrial mass and ATP production were not changed. In addition to the shear flow of 12.5 dynes/cm2, the expressions of EMT were compared at lower (6.25 dynes/cm2) and at higher (25 dynes/cm2) shear flow. The results showed that lower shear flow increased mesenchymal characteristics and higher shear flow increased epithelial characteristics. Shear flow reduces the malignancy of CRC in their metastatic dispersal that opens up new ways to improve cancer therapies by applying a mechanical shear flow device.

Acute resistance exercise combined with whole body vibration and blood flow restriction: Molecular and neurocognitive effects in late-middle-aged and older adults.

Limited research exists regarding the effects of resistance exercise (RE) combined with whole body vibration (WBV), blood flow restriction (BFR), or both on the neuropsychological performance of working memory (WM) in late-middle-aged and older adults and regarding the physiological mechanisms underlying this effect. This study thus explored the acute molecular and neurophysiological mechanisms underlying WM performance following RE combined with WBV, BFR, or both. Sixty-six participants were randomly assigned into a WBV, BFR, or WBV + BFR group. Before and after the participants engaged in a single bout of isometric RE combined with WBV, BFR, or both, this study gathered data on several neurocognitive measures of WM performance, namely, accuracy rate (AR), reaction time (RT), and brain event-related potential (specifically P3 latency and amplitude), and data on biochemical indices, such as the levels of insulin-like growth factor-1 (IGF-1), norepinephrine (NE), and brain-derived neurotrophic factor (BDNF). Although none of the RE modalities significantly affected RTs and P3 latencies, ARs and P3 amplitudes significantly improved in the WBV and WBV + BFR groups. The WBV + BFR group exhibited greater improvements than the WBV group did. Following acute RE combined with WBV, BFR, or both, IGF-1 and NE levels significantly increased in all groups, whereas BDNF levels did not change. Crucially, only the changes in NE levels were significantly correlated with improvements in ARs in the WBV + BFR and WBV groups. The findings suggest that combining acute RE with WBV, BFR, or both could distinctively mitigate neurocognitive decline in late-middle-aged and older adults.

Exploring the evolution of T cell function and diversity across different stages of non-small cell lung cancer.

The immune system plays a key role in detecting and fighting cancerous tumors. T cells are a crucial component in both natural and therapeutic cancer immunoediting responses, but it is unclear if they are the primary agents of these processes. In this study, patients with lung lesions detected by CT scan were selected, and their peripheral blood samples were analyzed for T cell population and serum cytokines/chemokines. T cell subtypes (CD3, CD4, CD8, CD27, CD28, CD45, CD45RA, CD57, CCR7, and PD1) and serum cytokines/chemokines (IL-2, IL-6, IL-10, IFN-γ, TGF-ß, TNFα, CXCL1, CXCL9, and CXCL12) were measured by flow cytometry and analysis before surgical resection or other cancer treatments. The frequency of T cell subpopulations in patients with lung cancer (n = 111) corresponded to those seen in patients with T cell exhaustion. As lung cancer progressed, the proportion of effector memory T cells decreased, while the proportion of naive T cells, PD-1, CD57+, CD28+CD27+, CD45RA+, and CD3+CD4+CCR7 increased. Circulating CD8+PD1+ T cells were positively correlated with intra-tumoral PD-L1 expression. Concurrently, serum levels of IL-2, TGF-ß, and CXCL9 decreased, while IL-6, IL-10, IFN-γ, and CXCL12 increased during the progression of lung cancer. In conclusion, T cell dysfunction is associated with cancer progression, particularly in advanced-stage lung cancer, and cancer immunoediting will provide early-stage cancer detection and further therapeutic strategies.

Impaired motor skills and proprioceptive function in Mandarin-speaking children with developmental language disorder.

This study examined proprioceptive acuity and its relationship with motor function in Mandarin-speaking children with and without developmental language disorder (DLD). Fifteen children aged 9-12 years with DLD and 15 age- and sex-matched typically developing (TD) children participated in this study. Children's motor function was assessed using the second edition of the Movement Assessment Battery for Children (MABC-2). Their proprioceptive acuity was measured based on the absolute error (i.e., proprioceptive bias) and variable error (i.e., proprioceptive precision) when performing joint position matching tasks. Compared with the TD group, the DLD group exhibited impaired motor function and poorer proprioceptive acuity, as evidenced by the lower scores on the MABC-2 and the higher rates of absolute and variable errors in the joint position matching tasks. A significant association between the proprioceptive bias (absolute error) and the MABC-2 total score was also observed in the combined cohort of children with and without DLD. We conclude that DLD is associated with proprioceptive dysfunction.

Motion sense sensitivity of the ankle is abnormal and correlated with motor performance in children with and without a probable developmental coordination disorder.

This study systematically examined ankle motion sense sensitivity and its relation to motor functions in children with and without a probable developmental coordination disorder (pDCD). Seventy-two children aged 10-11 years were recruited, including thirty-six children with pDCD and 36 age- and sex-matched typically developing (TD) children. Children placed their dominant foot on a passive ankle motion apparatus that induced plantar flexion of the ankle under nine constant velocities ranging between 0.15 and 1.35°/s. The adjusted movement detection time (ADT) to passive ankle motion was obtained to measure ankle motion sense sensitivity. The results showed that, in comparison to that in the TD group, ankle ADT was significantly increased by 22-59% for the range of velocities in the pDCD group. A correlation analysis showed that mean ADTs were significantly correlated with the manual dexterity (r = -0.33, p = 0.005) and balance (r = -0.24, p = 0.046) scores on the Movement Assessment Battery for Children (MABC-2) in the combined group. Similar correlations were found between the ADTs and the manual dexterity (r = -0.37, p = 0.028) and total motor (r = -0.34, p = 0.047) scores in the TD group. This study documents that ankle motion sense sensitivity to passive foot motion is reduced and is likely to contribute to poor motor performance in children with and without pDCD.

NIR-activated quercetin-based nanogels embedded with CuS nanoclusters for the treatment of drug-resistant biofilms and accelerated chronic wound healing.

We have developed multifunctional nanogels with antimicrobial, antioxidant, and anti-inflammatory properties, facilitating rapid wound healing. To prepare the multifunctional nanogels, we utilized quercetin (Qu) and a mild carbonization process to form carbonized nanogels (CNGs). These CNGs possess excellent antioxidative and bacterial targeting properties. Subsequently, we utilized the Qu-CNGs as templates to prepare nanogels incorporating copper sulfide (CuS) nanoclusters, further enhancing their functionality. Notably, the CuS/Qu-CNGs nanocomposites demonstrated an exceptional minimum inhibitory concentration against tested bacteria, approximately 125-fold lower than monomeric Qu or Qu-CNGs. This enhanced antimicrobial effect was achieved by leveraging near-infrared II (NIR-II) light irradiation. Additionally, the CuS/Qu-CNGs exhibited efficient penetration into the extracellular biofilm matrix, eradicating methicillin-resistant Staphylococcus aureus-associated biofilms in diabetic mice wounds. Furthermore, the nanocomposites were found to suppress proinflammatory cytokines, such as IL-1ß, at the wound sites while regulating the expression of anti-inflammatory factors, including IL-10 and TGF-ß1, throughout the recovery process. The presence of CuS/Qu-CNGs promoted angiogenesis, epithelialization, and collagen synthesis, thereby accelerating wound healing. Our developed CuS/Qu-CNGs nanocomposites have great potential in addressing the challenges associated with delayed wound healing caused by microbial pathogenesis.

Defensive responses: behaviour, the brain and the body.

Most animals live under constant threat from predators, and predation has been a major selective force in shaping animal behaviour. Nevertheless, defence responses against predatory threats need to be balanced against other adaptive behaviours such as foraging, mating and recovering from infection. This behavioural balance in ethologically relevant contexts requires adequate integration of internal and external signals in a complex interplay between the brain and the body. Despite this complexity, research has often considered defensive behaviour as entirely mediated by the brain processing threat-related information obtained via perception of the external environment. However, accumulating evidence suggests that the endocrine, immune, gastrointestinal and reproductive systems have important roles in modulating behavioural responses to threat. In this Review, we focus on how predatory threat defence responses are shaped by threat imminence and review the circuitry between subcortical brain regions involved in mediating defensive behaviours. Then, we discuss the intersection of peripheral systems involved in internal states related to infection, hunger and mating with the neurocircuits that underlie defence responses against predatory threat. Through this process, we aim to elucidate the interconnections between the brain and body as an integrated network that facilitates appropriate defensive responses to threat and to discuss the implications for future behavioural research.

Ligand Control of Dinitrosyl Iron Complexes for Selective Superoxide-Mediated Nitric Oxide Monooxygenation and Superoxide-Dioxygen Interconversion.

Through nitrosylation of [Fe-S] proteins, or the chelatable iron pool, a dinitrosyl iron unit (DNIU) [Fe(NO)2] embedded in the form of low-molecular-weight/protein-bound dinitrosyl iron complexes (DNICs) was discovered as a metallocofactor assembled under inflammatory conditions with elevated levels of nitric oxide (NO) and superoxide (O2-). In an attempt to gain biomimetic insights into the unexplored transformations of the DNIU under inflammation, we investigated the reactivity toward O2- by a series of DNICs [(NO)2Fe(µ-MePyr)2Fe(NO)2] (1) and [(NO)2Fe(µ-SEt)2Fe(NO)2] (3). During the superoxide-induced conversion of DNIC 1 into DNIC [(K-18-crown-6-ether)2(NO2)][Fe(µ-MePyr)4(µ-O)2(Fe(NO)2)4] (2-K-crown) and a [Fe3+(MePyr)x(NO2)y(O)z]n adduct, stoichiometric NO monooxygenation yielding NO2- occurs without the transient formation of peroxynitrite-derived •OH/•NO2 species. To study the isoelectronic reaction of O2(g) and one-electron-reduced DNIC 1, a DNIC featuring an electronically localized {Fe(NO)2}9-{Fe(NO)2}10 electronic structure, [K-18-crown-6-ether][(NO)2Fe(µ-MePyr)2Fe(NO)2] (1-red), was successfully synthesized and characterized. Oxygenation of DNIC 1-red leads to the similar assembly of DNIC 2-K-crown, of which the electronic structure is best described as paramagnetic with weak antiferromagnetic coupling among the four S = 1/2 {FeIII(NO-)2}9 units and S = 5/2 Fe3+ center. In contrast to DNICs 1 and 1-red, DNICs 3 and [K-18-crown-6-ether][(NO)2Fe(µ-SEt)2Fe(NO)2] (3-red) display a reversible equilibrium of "3 + O2- ⇋ 3-red + O2(g)", which is ascribed to the covalent [Fe(µ-SEt)2Fe] core and redox-active [Fe(NO)2] unit. Based on this study, the supporting/bridging ligands in dinuclear DNIC 1/3 (or 1-red/3-red) control the selective monooxygenation of NO and redox interconversion between O2- and O2 during reaction with O2- (or O2).

Liraglutide modulates adhesion molecules and enhances cell properties in three-dimensional cultures of olfactory ensheathing cells.

Cell transplantation using olfactory ensheathing cells (OECs) is a promising approach for nerve repair but there are numerous limitations with their delivery method. Three-dimensional (3D) cell culture systems potentially offer a powerful approach for cell production and delivery options. To further optimise the use of OECs, strategies to promote cell viability and maintain cell behaviours in 3D cultures become important. We previously demonstrated an anti-diabetic drug, liraglutide, could modulate OEC migration and re-model extracellular matrix in two-dimensional (2D) cultures. In the present study, we further investigated its beneficial effects in our 3D culture system using primary OECs. OECs treated with liraglutide at 100 nM showed improved cell viability and had modulated expression of N-cadherin and ß1-integrin (two important cell adhesion molecules). When formed into 3D spheroids, the pre-treated OECs generated spheroids with an increased volume and a decreased cell density compared to control spheroids. OECs that subsequently migrated out of the liraglutide pre-treated spheroids had higher capacity for migration with increased duration and length, which was attributed to a reduction in the pauses during the migration. Moreover, OECs that migrated out from liraglutide spheroids had a more bipolar morphology consistent with higher migratory capacity. In summary, liraglutide improved the viability of OECs, modulated cell adhesion molecules, and resulted in stable 3D cell constructs which conferred enhanced migratory capacity on the OECs. Overall, liraglutide may potentially improve the therapeutic use of OECs for neural repair by enhancing the generation of stable 3D constructs and increasing the migratory behaviour of OECs.

Developmental Coordination Disorder and Unhealthy Weight Status in Taiwanese Children: The Roles of Sex and Age.

This study aimed to provide up-to-date information regarding the estimated prevalence of developmental coordination disorder (DCD) in Taiwanese children. Their unhealthy weight status was also examined, as well as the roles of sex and age. This cross-sectional study recruited 825 children aged between 4 and 12 years and categorized them into either typically developing children (TD, >16th percentile) or children at risk for DCD (rDCD, ≤16th percentile) based on the result of the Movement Assessment Battery for Children-2nd edition. Body mass index was calculated to determine weight status (i.e., normal weight, underweight, overweight, and obesity). The estimated prevalence of rDCD was 9.7%. There were significantly more boys in the rDCD groups (p < 0.001). Additionally, preschool children with rDCD were at greater risk for being underweight. However, there was no significant group difference which was found for overweight/obesity. A lower prevalence of rDCD was found in this study. Nevertheless, children with rDCD may be more likely to be underweight in early childhood. Early intervention should be provided to target this population.

Systematic evaluation of a predator stress model of depression in mice using a hierarchical 3D-motion learning framework.

Investigation of the neurobiology of depression in humans depends on animal models that attempt to mimic specific features of the human disorder. However, frequently-used paradigms based on social stress cannot be easily applied to female mice which has led to a large sex bias in preclinical studies of depression. Furthermore, most studies focus on one or only a few behavioral assessments, with time and practical considerations prohibiting a comprehensive evaluation. In this study, we demonstrate that predator stress effectively induced depression-like behaviors in both male and female mice. By comparing predator stress and social defeat models, we observed that the former elicited a higher level of behavioral despair and the latter elicited more robust social avoidance. Furthermore, the use of machine learning (ML)-based spontaneous behavioral classification can distinguish mice subjected to one type of stress from another, and from non-stressed mice. We show that related patterns of spontaneous behaviors correspond to depression status as measured by canonical depression-like behaviors, which illustrates that depression-like symptoms can be predicted by ML-classified behavior patterns. Overall, our study confirms that the predator stress induced phenotype in mice is a good reflection of several important aspects of depression in humans and illustrates that ML-supported analysis can simultaneously evaluate multiple behavioral alterations in different animal models of depression, providing a more unbiased and holistic approach for the study of neuropsychiatric disorders.

Moderation of parental socioeconomic status on the relationship between birth health and developmental coordination disorder at early years.

Objective: This study investigated whether parental SES moderates the effect of birth health on Developmental Coordination Disorder (DCD) in preschool children. Methods: One hundred and twenty-two children aged 4 to 6 years were enrolled in the study. The Movement Assessment Battery for Children --2nd Edition (MABC-2) test was used to assess the motor coordination of children. They were preliminarily categorized into either the DCD (<=16th percentile, n = 23) or typically developing (TD) group (>16th percentile, n = 99) based on the testing results. All children in the DCD group were further confirmed to meet other diagnostic criteria of the DSM-V using the intellectual test and parental questionnaires. Moderation analysis was conducted using the PROCESS macro for SPSS, and 95% confidence intervals with a bootstrap procedure were calculated to identify the significant moderating effect. Results: Maternal education (unstandardized coefficient = 0.6805, SE = 0.3371, p < 0.05) and maternal employment status (unstandardized coefficient = 0.6100, SE = 0.3059, p < 0.05) were found to moderate the relationship between birth length and the probability of having DCD. Moreover, the relationship between birth weight and the probability of having DCD was moderated by the annual household income (unstandardized coefficient = -0.0043, SE = 0.0022, p < 0.05). Conclusion: The lower maternal education level and maternal unemployment strengthened the negative relationship between birth length and the probability of having DCD. Additionally, the negative relationship between birth weight and the probability of having DCD was statistically significant in high annual household salaries.

Table Tennis, as a Method of Sensorimotor Training, Induces Haptic and Motor Gains in Children With a Probable Developmental Coordination Disorder.

This study examined whether table tennis as a method of sensorimotor training improves haptic and motor function and to what extent haptic function gain correlates with changes in motor ability in children with probable developmental coordination disorder (pDCD). Children with pDCD were randomly assigned to the table tennis and nontraining control groups. The children in the table tennis group received 36 sessions of table tennis training, including ball balancing, hitting the ball against the wall, strokes, and serving. Haptic sensitivity, acuity, and motor function domains were measured. The results showed a 41.5% improvement in haptic sensitivity in children exposed to table tennis training compared with 2.8% in those without training. This improved haptic sensitivity significantly correlated with motor function gain, suggesting that somatosensory gains occur simultaneously with changes in motor function in children with pDCD. This novel upper limb motor training approach may be an interesting method of sensorimotor training in neurological rehabilitation in children with pDCD.

Not only motor skill performance but also haptic function is impaired in children with developmental language disorder.

BACKGROUND: Previous studies have found an association between motor immaturity and developmental language impairment in children. However, systematic investigations of somatosensory dysfunctions that might be linked to motor deficits in children with developmental language disorder (DLD) are lacking. AIMS: Examined haptic perception and motor skills in school-age children with DLD and typically-developing (TD) children. METHODS: Sixteen children with DLD and sixteen age-matched TD children performed a curvature detection task measuring haptic sensitivity and a curvature discrimination task measuring haptic acuity. The Movement Assessment Battery for Children, 2nd edition (MABC-2) was also conducted to evaluate children's motor ability. RESULTS: The results revealed elevated thresholds of both haptic detection (67.5%) and haptic discrimination (67.9%) in the DLD group when compared to the TD group. In addition, the children with DLD performed significantly less well on the manual dexterity of MABC-2. Finally, a lower haptic acuity was associated with poorer manual dexterity scores of MABC-2. CONCLUSIONS: This study demonstrates for the first time that not only motor skills, but also haptic function is altered in children with DLD. The observed association between manual dexterity and haptic acuity suggests a close relationship between haptic and motor skills in school-age children.

A New Drug Safety Signal Detection and Triage System Integrating Sequence Symmetry Analysis and Tree-Based Scan Statistics with Longitudinal Data.

Purpose: Development and evaluation of a drug-safety signal detection system integrating data-mining tools in longitudinal data is essential. This study aimed to construct a new triage system using longitudinal data for drug-safety signal detection, integrating data-mining tools, and evaluate adaptability of such system. Patients and Methods: Based on relevant guidelines and structural frameworks in Taiwan's pharmacovigilance system, we constructed a triage system integrating sequence symmetry analysis (SSA) and tree-based scan statistics (TreeScan) as data-mining tools for detecting safety signals. We conducted an exploratory analysis utilizing Taiwan's National Health Insurance Database and selecting two drug classes (sodium-glucose co-transporter-2 inhibitors (SGLT2i) and non-fluorinated quinolones (NFQ)) as chronic and episodic treatment respectively, as examples to test feasibility of the system. Results: Under the proposed system, either cohort-based or self-controlled mining with SSA and TreeScan was selected, based on whether the screened drug had an appropriate comparator. All detected alerts were further classified as known adverse drug reactions (ADRs), events related to other causes or potential signals from the triage algorithm, building on existing drug labels and clinical judgement. Exploratory analysis revealed greater numbers of signals for NFQ with a relatively low proportion of known ADRs; most were related to indication, patient characteristics or bias. No safety signals were found. By contrast, most SGLT2i signals were known ADRs or events related to patient characteristics. Four were potential signals warranting further investigation. Conclusion: The proposed system facilitated active and systematic screening to detect and classify potential safety signals. Countries with real-world longitudinal data could adopt it to streamline drug-safety surveillance.

Substrate-Gated Transformation of a Pre-Catalyst into an Iron-Hydride Intermediate [(NO)2(CO)Fe(µ-H)Fe(CO)(NO)2]- for Catalytic Dehydrogenation of Dimethylamine Borane.

Continued efforts are made on the development of earth-abundant metal catalysts for dehydrogenation/hydrolysis of amine boranes. In this study, complex [K-18-crown-6-ether][(NO)2Fe(µ-MePyr)(µ-CO)Fe(NO)2] (3-K-crown, MePyr = 3-methylpyrazolate) was explored as a pre-catalyst for the dehydrogenation of dimethylamine borane (DMAB). Upon evolution of H2(g) from DMAB triggered by 3-K-crown, parallel conversion of 3-K-crown into [(NO)2Fe(N,N'-MePyrBH2NMe2)]- (5) and an iron-hydride intermediate [(NO)2(CO)Fe(µ-H)Fe(CO)(NO)2]- (A) was evidenced by X-ray diffraction/nuclear magnetic resonance/infrared/nuclear resonance vibrational spectroscopy experiments and supported by density functional theory calculations. Subsequent transformation of A into complex [(NO)2Fe(µ-CO)2Fe(NO)2]- (6) is synchronized with the deactivated generation of H2(g). Through reaction of complex [Na-18-crown-6-ether][(NO)2Fe(η2-BH4)] (4-Na-crown) with CO(g) as an alternative synthetic route, isolated intermediate [Na-18-crown-6-ether][(NO)2(CO)Fe(µ-H)Fe(CO)(NO)2] (A-Na-crown) featuring catalytic reactivity toward dehydrogenation of DMAB supports a substrate-gated transformation of a pre-catalyst [(NO)2Fe(µ-MePyr)(µ-CO)Fe(NO)2]- (3) into the iron-hydride species A as an intermediate during the generation of H2(g).

Male and female mice display consistent lifelong ability to address potential life-threatening cues using different post-threat coping strategies.

BACKGROUND: Sex differences ranging from physiological functions to pathological disorders are developmentally hard-wired in a broad range of animals, from invertebrates to humans. These differences ensure that animals can display appropriate behaviors under a variety of circumstances, such as aggression, hunting, sleep, mating, and parental care, which are often thought to be important in the acquisition of resources, including territory, food, and mates. Although there are reports of an absence of sexual dimorphism in the context of innate fear, the question of whether there is sexual dimorphism of innate defensive behavior is still an open question. Therefore, an in-depth investigation to determine whether there are sex differences in developmentally hard-wired innate defensive behaviors in life-threatening circumstances is warranted. RESULTS: We found that innate defensive behavioral responses to potentially life-threatening stimuli between males and females were indistinguishable over their lifespan. However, by using 3 dimensional (3D)-motion learning framework analysis, we found that males and females showed different behavioral patterns after escaping to the refuge. Specifically, the defensive "freezing" occurred primarily in males, whereas females were more likely to return directly to exploration. Moreover, there were also no estrous phase differences in innate defensive behavioral responses after looming stimuli. CONCLUSIONS: Our results demonstrate that visually-evoked innate fear behavior is highly conserved throughout the lifespan in both males and females, while specific post-threat coping strategies depend on sex. These findings indicate that innate fear behavior is essential to both sexes and as such, there are no evolutionary-driven sex differences in defensive ability.

Cryptococcus gattii Infection as the Major Clinical Manifestation in Patients with Autoantibodies Against Granulocyte-Macrophage Colony-Stimulating Factor.

PURPOSE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are a predisposing factor for pulmonary alveolar proteinosis (PAP) and Cryptococcus gattii cryptococcosis. This study aimed to investigate clinical manifestations in anti-GM-CSF Ab-positive patients with C. gattii cryptococcosis and analyze the properties of anti-GM-CSF Abs derived from these patients and patients with PAP. METHODS: Thirty-nine patients diagnosed with cryptococcosis (caused by C. neoformans or C. gattii) and 6 with PAP were enrolled in the present study. Clinical information was obtained from medical records. Blood samples were collected for analysis of autoantibody properties. We also explored the National Health Insurance Research Database (NHIRD) of Taiwan to investigate the epidemiology of cryptococcosis and PAP. RESULTS: High titers of neutralizing anti-GM-CSF Abs were identified in 15 patients with cryptococcosis (15/39, 38.5%). Most anti-GM-CSF Ab-positive cryptococcosis cases had central nervous system (CNS) involvement (14/15, 93.3%). Eleven out of 14 (78.6%) anti-GM-CSF Ab-positive CNS cryptococcosis patients were confirmed to be infected with C. gattii, and PAP did not occur synchronously or metachronously in a single patient from our cohort. Exploration of an association between HLA and anti-GM-CSF Ab positivity or differential properties of autoantibodies from cryptococcosis patients and PAP yielded no significant results. CONCLUSION: Anti-GM-CSF Abs can cause two diseases, C. gattii cryptococcosis and PAP, which seldom occur in the same subject. Current biological evidence regarding the properties of anti-GM-CSF Abs cannot provide clues regarding decisive mechanisms. Further analysis, including more extensive cohort studies and investigations into detailed properties, is mandatory to better understand the pathogenesis of anti-GM-CSF Abs.

Synthesis and in situ sulfidation of molybdenum carbide MXene using fluorine-free etchant for electrocatalytic hydrogen evolution reactions.

Synthesizing MXenes from Mn+1AXn (MAX) phases using hazardous hydrogen fluoride is a common and effective method. However, fluorine termination on the basal planes and edges of the resulting MXenes is undesirable for the electrocatalytic hydrogen evolution reaction (HER), while oxygen (O), hydroxyl (OH), and sulfur (S) termination favors this reaction. Herein, we unveil a simple fluorine-free exfoliation and two-step vulcanization method for synthesizing molybdenum sulfide-modified molybdenum carbide (MoS2/Mo2CTx MXene, T = OH, O, S) for the HER in alkaline medium. Microwave-assisted hydrothermal treatment of the MAX phase (Mo3AlC2) with sodium hydroxide-sodium sulfide as an etching solution and thioacetamide as a source of sulfide ions enabled the selective dissolution of the aluminum (Al) layer and sulfidation of the surface Mo atoms to form amorphous MoS2. Thus, the vulcanization of Mo2CTx MXene resulted in the formation of MoS2/Mo2CTx MXene. The MoS2 formed on the surface of Mo2CTx provided enhanced stability by preventing oxidation. MoS2/Mo2CTx exhibited enhanced electrocatalytic activity toward the HER, mainly due to the O, OH, and amorphous MoS2 functionalities. The MoS2 sites on the surface exhibited an overpotential of 110 ± 7 mV at a current density of 10 mA cm-2 as a result of enhanced charge transfer and mass transfer. Thus, the sulfidation method demonstrated herein is capable of producing amorphous MoS2 structures on Mo2CTx MXene, which could be applied for the surface modification of other molybdenum-based nanomaterials or electrocatalysts to improve stability and enhance electrocatalytic activity.