Direction of leukocyte polarization and migration by the phosphoinositide-transfer protein TIPE2.

The polarization of leukocytes toward chemoattractants is essential for the directed migration (chemotaxis) of leukocytes. How leukocytes acquire polarity after encountering chemical gradients is not well understood. We found here that leukocyte polarity was generated by TIPE2 (TNFAIP8L2), a transfer protein for phosphoinositide second messengers. TIPE2 functioned as a local enhancer of phosphoinositide-dependent signaling and cytoskeleton remodeling, which promoted leading-edge formation. Conversely, TIPE2 acted as an inhibitor of the GTPase Rac, which promoted trailing-edge polarization. Consequently, TIPE2-deficient leukocytes were defective in polarization and chemotaxis, and TIPE2-deficient mice were resistant to leukocyte-mediated neural inflammation. Thus, the leukocyte polarizer is a dual-role phosphoinositide-transfer protein and represents a potential therapeutic target for the treatment of inflammatory diseases.

Prenatal and early childhood infections requiring hospitalization and risk of neurodevelopmental disorders in offspring: a population-based birth cohort study in Taiwan.

In utero and early childhood infections have been associated with an increased risk of neurodevelopmental disorders; however, the observed associations may be confounded by familial predispositions. This study examined the neurodevelopmental disorders attributable to maternal infections during pregnancy and early childhood infections during the first year of life, including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), tic disorders, and mental retardation (MR). We performed population and sibling comparison analyses to account for unmeasured familial confounding factors. We conducted a register-based cohort study with 2,885,662 individuals (comprising 1,864,660 full siblings) born in Taiwan between 2001 and 2018 and followed up until 2021. We employed Cox regression analysis to assess the association between in utero and early childhood infections requiring hospitalization and the subsequent risk of neurodevelopmental disorders. In the population analyses, an offspring exposed to maternal infection had an increased risk for ASD (hazard ratio (HR) = 1.19, 95% confidence interval (CI): 1.13-1.26), ADHD (HR = 1.14, 95% CI: 1.11-1.18), and MR (HR = 1.21, 95% CI: 1.13-1.30). These associations attenuated toward null in the sibling analyses. Individuals exposed to early childhood infection had an increased risk for ASD (HR = 1.13, 95% CI: 1.10-1.16), ADHD (HR = 1.16, 95% CI: 1.15-1.18), tic disorders (HR = 1.12, 95% CI: 1.09-1.15), and MR (HR = 1.64, 95% CI: 1.60-1.69) in the population analyses; these associations were also significant for ASD (HR = 1.14, 95% CI: 1.07-1.21) and MR (HR = 1.52, 95% CI: 1.44-1.62) in the sibling analyses. The association between maternal infection during pregnancy and offspring neurodevelopmental risk is largely due to familial confounding factors. Conversely, infection in early childhood may be attributable to it being a sensitive period and may play a role in the subsequent risk of ASD and MR.

Bodipy-based quinoline derivative as a highly Hg2+-selective fluorescent chemosensor and its potential applications.

A highly efficient sensor has been successfully developed using quinoline-based BODIPY compounds (8-quinoline-4,4-difluoro-4-boro-3a, 4a-diazaindacene (C1) and 7-hydroxy-8-quinoline-4,4-difluoro-4-boro-3a, 4a-diazindacene (C2) to detect Hg2+ ions. The sensor C1 exhibits remarkable selectivity in detecting Hg2+ with a limit of detection 3.06 × 10-8 mol/L. The developed chemical sensors have shown stability, cost-effectiveness, ease of preparation, and remarkable selectivity towards Hg2+ ions compared to other commonly occurring metal ions. The total recovery of the sensor C1 can be achieved by using a 0.1 mol/L solution of KI. The proposed sensor C1 has been applied to determine Hg2+ in tap and distilled water, yielding excellent results. In addition, the binding mode of C1-Hg2+ and C2-Hg2+ complexes was a 1:1 ratio confirmed by mass spectra, Job's plot, and DFT study. Moreover, the sensor C1 successfully applied for the biological studies results in negligible cytotoxicity, which demonstrates it can be used to determine Hg2+ in HT22 cells.

Synthesis of functionalized mesoporous silica nanoparticles for colorimetric and fluorescence sensing of selective metal (Fe3+) ions in aqueous solution.

The fabrication of red fluorescent hybrid mesoporous silica-based nanosensor materials has promised the bioimaging and selective detection of toxic pollutants in aqueous solutions. In this study, we present a hybrid mesoporous silica nanosensor in which the propidium iodide (PI) was used to conveniently integrate into the mesopore walls using bis(trimethoxysilylpropyl silane) precursors. Various characterization techniques including X-ray diffraction (XRD), Fourier-transform infrared (FTIR), N2 adsorption-desorption, zeta potential, particle size analysis, thermogravimetric, and UV-visible analysis were used to analyze the prepared materials. The prepared PI integrated mesoporous silica nanoparticles (PI-MSNs) selective metal ion sensing capabilities were tested with a variety of heavy metal ions (100 mM), including Ni2+, Cd2+, Co2+, Zn2+, Cr3+, Cu2+, Al3+, Mg2+, Hg2+ and Fe3+ ions. Among the investigated metal ions, the prepared PI-MSNs demonstrated selective monitoring of Fe3+ ions with a significant visible colorimetric pink color change into orange and quenching of pink fluorescence in an aqueous suspension. The selective sensing behavior of PI-MSNs might be due to the interaction of Fe3+ ions with the integrated PI functional fluorophore present in the mesopore walls. Therefore, we emphasize that the prepared PI-MSNs could be efficient for selective monitoring of Fe3+ ions in an aqueous solution and in the biological cellular microenvironment.

Enhanced Stability of Melt-Processable Organic-Inorganic Hybrid Manganese Halides for X-Ray Imaging.

Mn-based metal halides scintillators with high photoluminescence quantum yield (PLQY) have recently emerged as promising large-size candidates for X-ray imaging but still remains as difficult challenge in stability and high processing temperatures. Here, three manganese halides are designed by introducing branched chains into organic cations and extending the carbon chains, namely (i-PrTPP)2MnBr4, (i-BuTPP)2MnBr4 and (i-AmTPP)2MnBr4, successfully lowered the melting point of manganese halides to 120.2 °C. Three materials show striking light yields of 59 000, 40 000, and 52 000 photons MeV-1, respectively. The lowest detection limits are 42.30, 50.92, and 45.71 nGy s-1, respectively. Meanwhile, compared to their counterparts with linear carbon chains, the introduction of branched chains has significantly enhanced the stability of the scintillators in the glass state. A transparent glass has been prepared using a melt-quenching method, which exhibited 80% transmittance at 400-700 nm. The glass is utilized for X-ray imaging, achieving a high spatial resolution up to 46.6 lp mm-1. This result provides a new approach to enhancing the performance of such scintillator materials.

Staphylococcus aureus foldase PrsA contributes to the folding and secretion of protein A.

BACKGROUND: Staphylococcus aureus secretes a variety of proteins including virulence factors that cause diseases. PrsA, encoded by many Gram-positive bacteria, is a membrane-anchored lipoprotein that functions as a foldase to assist in post-translocational folding and helps maintain the stability of secreted proteins. Our earlier proteomic studies found that PrsA is required for the secretion of protein A, an immunoglobulin-binding protein that contributes to host immune evasion. This study aims to investigate how PrsA influences protein A secretion. RESULTS: We found that in comparison with the parental strain HG001, the prsA-deletion mutant HG001ΔprsA secreted less protein A. Deleting prsA also decreased the stability of exported protein A. Pulldown assays indicated that PrsA interacts with protein A in vivo. The domains in PrsA that interact with protein A are mapped to both the N- and C-terminal regions (NC domains). Additionally, the NC domains are essential for promoting PrsA dimerization. Furthermore, an immunoglobulin-binding assay revealed that, compared to the parental strain HG001, fewer immunoglobulins bound to the surface of the mutant strain HG001ΔprsA. CONCLUSIONS: This study demonstrates that PrsA is critical for the folding and secretion of protein A. The information derived from this study provides a better understanding of virulent protein export pathways that are crucial to the pathogenicity of S. aureus.

Protecting stable biological nomenclatural systems enables universal communication: A collective international appeal.

The fundamental value of universal nomenclatural systems in biology is that they enable unambiguous scientific communication. However, the stability of these systems is threatened by recent discussions asking for a fairer nomenclature, raising the possibility of bulk revision processes for "inappropriate" names. It is evident that such proposals come from very deep feelings, but we show how they can irreparably damage the foundation of biological communication and, in turn, the sciences that depend on it. There are four essential consequences of objective codes of nomenclature: universality, stability, neutrality, and transculturality. These codes provide fair and impartial guides to the principles governing biological nomenclature and allow unambiguous universal communication in biology. Accordingly, no subjective proposals should be allowed to undermine them.

Parametric Analysis of Donor Activation for Glycosylation Reactions.

The chemical synthesis of complex oligosaccharides relies on efficient and highly reproducible glycosylation reactions. The outcome of a glycosylation is contingent upon several environmental factors, such as temperature, acidity, the presence of residual moisture, as well as the steric, electronic, and conformational aspects of the reactants. Each glycosylation proceeds rapidly and with a high yield within a rather narrow temperature range. For better control over glycosylations and to ensure fast and reliable reactions, a systematic analysis of 18 glycosyl donors revealed the effect of reagent concentration, water content, protecting groups, and structure of the glycosyl donors on the activation temperature. With these insights, we parametrize the first step of the glycosylation reaction to be executed reliably and efficiently.

Melatonin increases Olaparib sensitivity and suppresses cancer-associated fibroblast infiltration via suppressing the LAMB3-CXCL2 axis in TNBC.

Triple-negative breast cancer (TNBC) is the most malignant breast cancer subtype, characterized with high aggressiveness and a high recurrence rate. Olaparib is the first US Food and Drug Administration-approved poly(ADP ribose) polymerase (PARP) inhibitor (PARPi) to treat breast cancer patients with a germline BRCA1 or BRCA2 mutation. However, resistance to Olaparib treatment restricts the therapeutic effects, and thus novel therapeutics are urgently required. In the present study, we identified that the combination of melatonin and Olaparib synergistically enhanced the sensitivity of TNBC cells. Moreover, melatonin exerted promising antitumor activities in Olaparib-resistant cells, implying the potential for its clinical application. An RNA-sequencing analysis revealed that melatonin treatment downregulated laminin subunit beta 3 (LAMB3) expression. Genetic ablation of LAMB3 significantly increased Olaparib sensitivity, and subsequently suppressed proliferation, epithelial-to-mesenchymal transition (EMT)-related gene expressions, and aggressiveness of breast cancer cells. Accordingly, LAMB3 expression was positively correlated with C-X-C motif chemokine ligand 2 (CXCL2), and they collaboratively promoted cancer-associated fibroblast (CAF) infiltration. An in vivo study demonstrated that combined treatment with melatonin and Olaparib showed enhanced inhibitory efficacy against tumor growth, LAMB3 expression, CXCL2 levels, and CAF infiltration compared to single treatment groups, and combined treatment with melatonin and Olaparib significantly ameliorated the immunosuppressive tumor microenvironment. These findings illustrate a promising therapeutic strategy using melatonin to overcome Olaparib resistance and activate antitumor immunity via attenuating the LAMB3-CXCL2 axis in breast cancer patients.

Oscillatory correlates of threat imminence during virtual navigation.

The Predatory Imminence Continuum Theory proposes that defensive behaviors depend on the proximity of a threat. While the neural mechanisms underlying this proposal are well studied in animal models, it remains poorly understood in humans. To address this issue, we recorded EEG from 24 (15 female) young adults engaged in a first-person virtual reality Risk-Reward interaction task. On each trial, participants were placed in a virtual room and presented with either a threat or reward conditioned stimulus (CS) in the same room location (proximal) or different room location (distal). Behaviorally, all participants learned to avoid the threat-CS, with most using the optimal behavior to actively avoid the proximal threat-CS (88% accuracy) and passively avoid the distal threat-CS (69% accuracy). Similarly, participants learned to actively approach the distal reward-CS (82% accuracy) and to remain passive to the proximal reward-CS (72% accuracy). At an electrophysiological level, we observed a general increase in theta power (4-8 Hz) over the right posterior channel P8 across all conditions, with the proximal threat-CS evoking the largest theta response. By contrast, distal cues induced two bursts of gamma (30-60 Hz) power over midline-parietal channel Pz (200 msec post-cue) and right frontal channel Fp2 (300 msec post-cue). Interestingly, the first burst of gamma power was sensitive to the distal threat-CS and the second burst at channel Fp2 was sensitive to the distal reward-CS. Together, these findings demonstrate that oscillatory processes differentiate between the spatial proximity information during threat and reward encoding, likely optimizing the selection of the appropriate behavioral response.

Human life expectancy and season of birth in Taiwan: A retrospective cohort study.

Prior research has indicated a correlation between the birth season and life expectancy; however, many of these studies did not sufficiently account for comorbidities. In this comprehensive investigation, we aimed to meticulously explore the association between the birth month and life expectancy, giving due consideration to comorbidities. We used a robust dataset derived from Taiwan's National Health Insurance Research Database (2000-2013), which allowed us to conduct a thorough examination. We divided our participants into four groups based on their season of birth: spring, summer, autumn, and winter. Propensity score matching was used to ensure an equitable distribution of demographic and clinical characteristics across the groups. Propensity scores were computed using logistic regression. Our model incorporated a broad range of demographic factors and comorbidities, providing rigorous adjustment for potential confounders. Our findings revealed a significantly increased risk of all-cause mortality among individuals born in spring, even after stringent adjustment for demographic factors and comorbidities. People born in spring demonstrated a 1.05-fold increase in the risk of all-cause mortality, with a hazard ratio of 1.05 and a 95% confidence interval of 1.01-1.09. Our study provides compelling evidence that helps understand the potential long-term impacts of a person's birth season, which acts as a proxy for pregnancy / early-life environmental exposure, on life expectancy. These findings underscore the crucial need for additional research to illuminate the underlying biological and environmental mechanisms linking the birth season and lifespan of a person. The elucidation of these links could guide the development of innovative health promotion and disease prevention strategies that are tailored to an individual's birth season.

Mechanochemical Synthesis of Cuprous Complexes for X-ray Scintillation and Imaging.

Cuprous complex scintillators show promise for X-ray detection with abundant raw materials, diverse luminescent mechanisms, and adjustable structures. However, their synthesis typically requires a significant amount of organic solvents, which conflict with green chemistry principles. Herein, we present the synthesis of two high-performance cuprous complex scintillators using a simple mechanochemical method for the first time, namely [CuI(PPh3)2R] (R = 4-phenylpyridine hydroiodide (PH, Cu-1) and 4-(4-bromophenyl)pyridine hydroiodide (PH-Br, Cu-2). Both materials demonstrated remarkable scintillation performances, exhibiting radioluminescence (RL) intensities 1.52 times (Cu-1) and 2.52 times (Cu-2) greater than those of Bi4Ge3O12 (BGO), respectively. Compared to Cu-1, the enhanced RL performance of Cu-2 can be ascribed to its elevated quantum yield of 51.54%, significantly surpassing that of Cu-1 at 37.75%. This excellent luminescent performance is derived from the introduction of PH-Br, providing a more diverse array of intermolecular interactions that effectively constrain molecular vibration and rotation, further suppressing the nonradiative transition process. Furthermore, Cu-2 powder can be prepared into scintillator film with excellent X-ray imaging capabilities. This work establishes a pathway for the rapid, eco-friendly, and cost-effective synthesis of high-performance cuprous complex scintillators.

Comparison of Demographic and Clinical Characteristics of Taiwan Biobank Participants with Nonparticipants.

BACKGROUND: This study investigated fundamental demographic variables within the Taiwan Biobank (TWBB) and compared them with national demographic statistics. Additionally, a matched cohort analysis compared TWBB participants with nonparticipants to uncover disparities in sociodemographic and clinical characteristics. METHODS: A total of 128,663 individuals aged 30 to 70 without cancer were recruited within the TWBB, and 514,652 nonparticipants matched by age and sex were randomly selected from the National Health Insurance claims database. Sociodemographic variables, healthcare utilization metrics, underlying medical conditions, and subsequent mortality and cancer risk were analyzed. RESULTS: TWBB participants were more likely to be female, older, married, higher educated, with higher incomes, and urban residency. Healthcare utilization metrics showed minimal differences. Pre-cohort entry, TWBB participants had a higher prevalence of certain medical conditions, such as peptic ulcer disease, osteoarthritis, osteoporosis, and uterine leiomyoma in females. During follow-up periods, elevated mortality rates were observed among TWBB participants but decreased cancer risk. CONCLUSION: The TWBB cohort exhibits disparities in sociodemographic and health-related attributes compared to the general population, comprising older, females, married, higher educated, higher income, and predominantly in urban areas. While mortality rates are slightly elevated within the TWBB cohort, cancer incidence rates are lower. Despite limitations in representativeness, the TWBB's size and exposure measures offer valuable insights into associations between exposures and health conditions.

Cul3-KLHL20 Ubiquitin Ligase Governs the Turnover of ULK1 and VPS34 Complexes to Control Autophagy Termination.

Autophagy, a cellular self-eating mechanism, is important for maintaining cell survival and tissue homeostasis in various stressed conditions. Although the molecular mechanism of autophagy induction has been well studied, how cells terminate autophagy process remains elusive. Here, we show that ULK1, a serine/threonine kinase critical for autophagy initiation, is a substrate of the Cul3-KLHL20 ubiquitin ligase. Upon autophagy induction, ULK1 autophosphorylation facilitates its recruitment to KLHL20 for ubiquitination and proteolysis. This autophagy-stimulated, KLHL20-dependent ULK1 degradation restrains the amplitude and duration of autophagy. Additionally, KLHL20 governs the degradation of ATG13, VPS34, Beclin-1, and ATG14 in prolonged starvation through a direct or indirect mechanism. Impairment of KLHL20-mediated regulation of autophagy dynamics potentiates starvation-induced cell death and aggravates diabetes-associated muscle atrophy. Our study identifies a key role of KLHL20 in autophagy termination by controlling autophagy-dependent turnover of ULK1 and VPS34 complex subunits and reveals the pathophysiological functions of this autophagy termination mechanism.

Thiamethoxam dynamics in pepper plants: Deciphering deposition and dissipation pattern across diverse planting modes and regions.

To reduce the application dosage of thiamethoxam (TMX), we investigated the deposition and dissipation patterns in a pepper-planted ecosystem under different planting modes across four regions in China, namely Hainan (HN), Zhejiang (ZJ), Anhui (AH) and Hebei (HB). This study focused on the deposition and dissipation of TMX at concentrations of 63.00, 47.25, 31.50, 23.63 and 15.75 g a.i.hm-2. As the application dose increased, the deposition amount of TMX initially increased in the plants and cultivated soil, showing obvious geographic differences in four cultivation areas. Surprisingly, the initial amount of TMX deposited the pepper-cultivated greenhouse of ZJ and AH was 1.1-2.1-fold and 1.0-3.6-fold higher than that in the open field system at the same application dose, respectively. In pepper leaves, stems, fruits and soil, the dissipation exhibited rapid growth and then slowed. However, the residual concentration showed an increasing trend, followed by a subsequent decrease in the pepper roots. In different planting regions, the dissipation rate of TMX followed the order HN > ZJ > AH > HB in pepper plants and cultivated soil. In comparison to the open field, the total TMX retention rate in greenhouse was higher, indicating overall greater persistence in the greenhouse conditions. These findings reveal the deposition and dissipation characteristics of TMX within the pepper-field ecosystem, offering a significant contribution to the risk assessment of pesticides.

Three chemosensory proteins enriched in antennae and tarsi of Rhaphuma horsfieldi differentially contribute to the binding of insecticides.

Antennae and legs (primarily the tarsal segments) of insects are the foremost sensory organs that contact a diverse range of toxic chemicals including insecticides. Binding proteins expressed in the two tissues are potential molecular candidates serving as the binding and sequestering of insecticides, like chemosensory proteins (CSPs). Insect CSPs endowed with multiple roles have been suggested to participate in insecticide resistance, focusing mainly on moths, aphids and mosquitos. Yet, the molecular underpinnings underlying the interactions of cerambycid CSPs and insecticides remain unexplored. Here, we present binding properties of three antenna- and tarsus-enriched RhorCSPs (RhorCSP1, CSP2 and CSP3) in Rhaphuma horsfieldi to eight insecticide classes totaling 15 chemicals. From the transcriptome of this beetle, totally 16 CSP-coding genes were found, with seven full-length sequences. In phylogeny, these RhorCSPs were distributed dispersedly in different clades. Expression profiles revealed the abundant expression of RhorCSP1, CSP2 and CSP3 in antennae and tarsi, thus as representatives for studying the protein-insecticide interactions. Binding assays showed that the three RhorCSPs were tuned differentially to insecticides but exhibited the highest affinities with hexaflumuron, chlorpyrifos and rotenone (dissociation constants <13 µM). In particular, RhorCSP3 could interact strongly with 10 of tested insecticides, of which four residues (Tyr25, Phe42, Val65 and Phe68) contributed significantly to the binding of six, four, three and four ligands, respectively. Of these, the binding of four mutated RhorCSP3s to a botanical insecticide rotenone was significantly weakened compared to the wildtype protein. Furthermore, we also evidenced that RhorCSP3 was a broadly-tuned carrier protein in response to a wide variety of plant odorants outside insecticides. Altogether, our findings shed light on different binding mechanisms and odorant-tuning profiles of three RhorCSPs in R. horsfieldi and identify key residues of the RhorCSP3-insecticide interactions.

Effectiveness of Cold Therapy for Pain and Anxiety Associated with Chest Tube Removal: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: To assess the effectiveness of cold therapy for pain and anxiety associated with chest tube removal. DESIGN: A Systematic review and meta-analysis of randomized controlled trials. DATA SOURCES: Articles were searched from Cochrane Library, PubMed, Embase, CINAHL, ProQuest, Airiti Library, China National Knowledge Infrastructure, and the National Digital Library of Theses and Dissertations in Taiwan. REVIEW/ANALYSIS METHODS: Eight electronic databases were searched from inception to August 20, 2022. The Cochrane Risk of Bias 2.0 tool was used to assess the quality of the included studies. Using a random-effects model, we calculated Hedges' g and its associated confidence interval to evaluate the effects of cold therapy. Cochrane's Q test and an I2 test were used to detect heterogeneity, and moderator and meta-regression analyses were conducted to explore possible sources of heterogeneity. Publication bias was assessed using a funnel plot, Egger's test, and trim-and-fill analysis. RESULTS: We examined 24 trials involving 1,821 patients. Cold therapy significantly reduced pain during and after chest tube removal as well as anxiety after chest tube removal (Hedges' g: -1.28, -1.27, and -1.80, respectively). Additionally, the effect size of cold therapy for reducing anxiety after chest tube removal was significantly and positively associated with that of cold therapy for reducing pain after chest tube removal. CONCLUSIONS: Cold therapy can reduce pain and anxiety associated with chest tube removal.

Nobiletin derivative, 5-acetoxy-6,7,8,3',4'-pentamethoxyflavone, inhibits neuroinflammation through the inhibition of TLR4/MyD88/MAPK signaling pathways and STAT3 in microglia.

OBJECTIVE: Microglia in the central nervous system regulate neuroinflammation that leads to a wide range of neuropathological alterations. The present study investigated the anti-neuroinflammatory properties of nobiletin (Nob) derivative, 5-acetoxy-6,7,8,3',4'-pentamethoxyflavone (5-Ac-Nob), in lipopolysaccharide (LPS)-activated BV2 microglia. MATERIALS AND METHODS: By using the MTT assay, Griess method, flow cytometry, and enzyme-linked immunosorbent assay (ELISA), we determined the cell viability, the levels of nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory factors (interleukin 1 beta; IL-1ß, interleukin 6; IL-6, tumor necrosis factor alpha; TNF-α and prostaglandin E2; PGE2) in LPS-stimulated BV2 microglia. Toll-like receptor 4 (TLR4)-mediated myeloid differentiation primary response gene 88 (MyD88)/nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK) signaling pathway and signal transducer and activator of transcription 3 (STAT3) were measured by western blotting. Analysis of NO generation and mRNA of pro-inflammatory cytokines was confirmed in the zebrafish model. RESULTS: 5-Ac-Nob reduced cell death, the levels of NO, ROS, inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and pro-inflammatory factors in LPS-activated BV-2 microglial cells. TLR4-mediated MyD88/NF-κB and MAPK pathway (p38, ERK and JNK) after exposure to 5-Ac-Nob was also suppressed. Moreover, 5-Ac-Nob inhibited phosphorylated STAT3 proteins expression in LPS-induced BV-2 microglial cells. Furthermore, we confirmed that 5-Ac-Nob decreased LPS-induced NO generation and mRNA of pro-inflammatory cytokines in the zebrafish model. CONCLUSIONS: Our findings suggest that 5-Ac-Nob represses neuroinflammatory responses by inhibiting TLR4-mediated signaling pathway and STAT3. As a result of these findings, 5-Ac-Nob has potential as an anti-inflammatory agent against microglia-mediated neuroinflammatory disorders.

Acute mountain sickness on Jade Mountain: Results from the real-world practice (2018-2019).

Acute mountain sickness (AMS) is initiated in response to a hypoxic and hypobaric environment at a high altitude. The precise prevalence of AMS in Jade Mountain climbers remained largely unknown, particularly data obtained from real medical consultations. An overnight stay at the Pai-Yun Lodge (3402 m) is usually required before an ascent of the Jade Mountain. Since 2004, a Pai-Yun Clinic has been established in the Pai-Yun Lodge. The Pai-Yun Clinic provided regular and emergency medical service every weekend. We conducted a retrospective study by using medical records from the Pai-Yun Clinic between 2018 and 2019. A total of 1021 patients were enrolled, with 56.2 % males. Different age groups were 3.2 %, 54.5 %, 37.9 %, and 4.4 % in <20, 20-39, 40-59, and ≥60 years, respectively. There were 582 (57.0 %) patients diagnosed to have AMS (230 [39.5 %] were mild type and 352 [60.5 %] were severe type). The factors associated with AMS development included young age, absence of climbing history (>3000 m) within the last 3 months, first climbing (>3000 m) experience, taking preventive medication, low oxygen saturation, and a high Lake Louise AMS score (LLAMSS). The factors associated with AMS severity included absence of taking preventive medication, low oxygen saturation, and a high LLAMSS. Approximately 15 % of Jade Mountain climbers needed medical service, of which 60 % had AMS. 60 % of patients with AMS must require oxygen supply or medication prescription. Oxygen saturation measure and LLAMSS evaluation are reasonable tools to predict the occurrence and severity of AMS on Jade Mountain.

Treatment withdrawal experiences of women with breast cancer: A phenomenological study.

AIM: To obtain an in-depth understanding of the lived experiences, values, and beliefs of Taiwanese women with breast cancer who withdrew from cancer treatment. BACKGROUND: Fear of side effects, negative experiences and personal beliefs were identified as reasons for withdrawing from cancer treatments. Body-mind consciousness and body autonomy play a crucial role in cancer treatment decisions. DESIGN: Descriptive phenomenological approach. METHODS: We conducted semi-structured, face-to-face and in-depth interviews with 16 women diagnosed with breast cancer. Participants were purposefully selected from the Cancer Registry database. Employing a phenomenological approach, our aim was to explore the lived experiences of these individuals. Data analysis followed Giorgi's five-step process. To ensure a comprehensive report the COREQ checklist was applied. FINDINGS: 'The Determination to Preserve Me' is the essence of treatment withdrawal, identified by three themes and seven sub-themes. 'Raising Body-Mind Consciousness' was generated using body autonomy and preventing repeated psychological trauma from the participant's view. Their lifestyles, maintaining the family role, and returning to a normal trajectory help develop 'Maintaining Stability for Being a Patient and a Family Carer'. 'Self-Defending Against the Body Harm' was generated by concerns about maintaining health and preventing harm. CONCLUSION: Women's behaviours became transformed by suffering. Actions were influenced by physical and psychological distress, misconceptions about treatments, and appearance changes by self-determination through self-protection. RELEVANCE TO CLINICAL PRACTICE: Healthcare professionals should respect women's autonomy and work collaboratively to ensure their decision-making with accurate information and awareness of the potential risks and benefits of treatment withdrawal need to concern.