Climate Change Projections for Stroke Incidence in Taiwan: Impact of 2 °C and 4 °C Global Warming Level.

OBJECTIVES: This study aimed to establish the exposure-lag-response effect between daily maximum temperature and stroke-related emergency department visits and to project heat-induced stroke impacts under global warming levels (GWL) of 2 °C and 4 °C. METHODS: Stroke-related emergency department visits in Taiwan from 2001 to 2020 were identified using the National Health Insurance Research Database (NHIRD). The study population consisted of 1,100,074 initial stroke cases matched with 2,200,148 non-stroke controls. We employed Distributed Lag Nonlinear Models (DLNM) in a case-crossover study to investigate the association between temperature and stroke. Generalized Estimating Equations (GEE) models with a Poisson function were used to correlate high-temperature exposure with annual stroke incidence rates. Projections were made under two global warming scenarios, GWL 2.0 °C and 4.0 °C, using Coupled General Circulation Model (GCMs). Baseline data from 1995 to 2014 were transformed for spatial distribution at the township level. Geographic Information System (GIS) spatial analysis was performed using Quantum GIS 3.2.0 software. RESULTS: DLNM exposure-lag-response effect revealed that daily maximum temperature exceeding 34 °C significantly increased the risk of stroke-related emergency department visits, particularly for ischemic stroke. Under the 2 °C GWL scenario, the frequency of days with temperatures surpassing 34 °C is projected to rise substantially by the median year of 2042, with a further increase to 92.6 ± 18.0 days/year by 2065 under the 4 °C GWL scenario. Ischemic stroke showed the highest increase in temperature-related incidence rates, notably rising from 7.80% under the GWL 2 °C to 36.06% under the GWL 4 °C. Specifically, the annual temperature-related incidence rate for ischemic stroke is expected to increase significantly by 2065. Regions such as Taichung, Hsinchu, Yilan, and Taitung demonstrated pronounced changes in heat-related ischemic stroke incidence under the GWL 4 °C. CONCLUSIONS: The findings emphasize the importance of addressing temperature-related stroke risks, particularly in regions projected to experience significant temperature increases. Effective mitigation strategies are crucial to reduce the impact of rising temperatures on stroke incidence and safeguard public health.

The association of psychological and trauma-related factors with biological and facial aging acceleration: evidence from the UK Biobank.

BACKGROUND: Psychological and trauma-related factors are associated with many diseases and mortality. However, a comprehensive assessment of the association between psycho-trauma exposures and aging acceleration is currently lacking. METHODS: Using data from 332,359 UK Biobank participants, we calculated biological aging acceleration, indexed by the presence of leukocyte telomere length (LTL) deviation (i.e., the difference between genetically determined and observed LTL > 0). The acceleration of facial aging (i.e., looking older than the chronological age) was assessed using a self-report question. Then, we estimated the associations of each psycho-trauma factor with biological and facial aging acceleration, using logistic regression models adjusted for multiple important covariates. Furthermore, restricted to 99,180 participants with complete psychological and trauma-related data, we identified clusters of individuals with distinct psycho-trauma patterns using the latent class analysis method and assessed their associations with aging acceleration using similar models. RESULTS: We observed most of the studied psycho-trauma factors were associated with biological and facial aging acceleration. Compared to the "Absence of trauma and psychopathology" cluster, the "adverse childhood experiences (ACEs) with psychopathology" cluster showed strong associations with those aging measurements (odds ratio [OR] = 1.13 [1.05 - 1.23] for biological and 1.52 [1.18 - 1.95] for facial aging acceleration), while no such association was observed for the "ACEs without psychopathology" cluster (1.04 [0.99 - 1.09] and 1.02 [0.84 - 1.24]. CONCLUSIONS: Our study demonstrated significant associations of psycho-trauma factors with both biological and facial aging acceleration. The differential aging consequences observed among ACEs exposed individuals with and without psychopathology prompt interventions aimed to improve individuals' psychological resilience to prevent aging acceleration.

Identifying prognostic predictors for postoperative pituitary neuroendocrine tumour recurrence: an integrated clinical, radiological, and immunohistochemistry assessment.

OBJECTIVE: Pituitary neuroendocrine tumours (PitNETs) are the second most common type of intracranial tumour. Several studies have explored the prognostic factors for PitNETs. However, prognostic factors for postoperative PitNET recurrence remain not fully understood. This study aimed to explore potential prognostic factors for PitNET recurrence, such as surrounding tissue invasion and the extent of surgical resection in patients with postoperative PitNETs. METHODS: We included 106 patients who underwent PitNET surgery between 2013 and 2018, dividing them into two groups: those with recurrence and those without recurrence. Tumours were classified based on demographics, neuroradiological, and immunohistological characteristics. Univariate and multivariate analyses were used to determine factors predicting recurrence. Kaplan-Meier plots and log-rank tests were used to analyse each independent factor based on the cumulative 5-year recurrence rate. RESULTS: During the 5-year follow-up period, 29.2% of the patients (n = 31) had disease recurrence. Univariate analysis showed that predictors of recurrence included cavernous and sphenoid sinus invasions, optic chiasm compression, larger tumour volume, giant adenoma >4 cm, and gross total resection (GTR). Multivariate analysis showed that lactotroph tumour type, sphenoid sinus invasion, and GTR were independent predictors. Kaplan-Meier analysis revealed significant differences in the 5-year recurrence rate among the three independent predictors, with significantly lower recurrence rate in patients with lactotroph tumours and GTR, and a significantly higher recurrence risk in patients with sphenoid sinus invasion. CONCLUSIONS: Lactotroph tumour type, sphenoid sinus invasion, and GTR are independent predictors of postoperative PitNET recurrence. This study provides insights into the factors affecting postoperative PitNET recurrence.

PitNETs are the second most common intracranial tumour typePrognostic factors for postoperative PitNET recurrence remain not fully understoodWe explored potential prognostic factors in patients with postoperative PitNETsProlactin secretion and GTR failure were independent recurrence predictorsProliferative factors did not correlate with recurrence.

Customizable Colorimetric Sensor Array via a High-Throughput Robot for Mitigation of Humidity Interference in Gas Sensing.

One challenge for gas sensors is humidity interference, as dynamic humidity conditions can cause unpredictable fluctuations in the response signal to analytes, increasing quantitative detection errors. Here, we introduce a concept: Select humidity sensors from a pool to compensate for the humidity signal for each gas sensor. In contrast to traditional methods that extremely suppress the humidity response, the sensor pool allows for more accurate gas quantification across a broader range of application scenarios by supplying customized, high-dimensional humidity response data as extrinsic compensation. As a proof-of-concept, mitigation of humidity interference in colorimetric gas quantification was achieved in three steps. First, across a ten-dimensional variable space, an algorithm-driven high-throughput experimental robot discovered multiple local optimum regions where colorimetric humidity sensing formulations exhibited high evaluations on sensitivity, reversibility, response time, and color change extent for 10-90% relative humidity (RH) in room temperature (25 °C). Second, from the local optimum regions, 91 sensing formulations with diverse variables were selected to construct a parent colorimetric humidity sensor array as the sensor pool for humidity signal compensation. Third, the quasi-optimal sensor subarrays were identified as customized humidity signal compensation solutions for different gas sensing scenarios across an approximately full dynamic range of humidity (10-90% RH) using an ingenious combination optimization strategy, and two accurate quantitative detections were attained: one with a mean absolute percentage error (MAPE) reduction from 4.4 to 0.75% and the other from 5.48 to 1.37%. Moreover, the parent sensor array's excellent humidity selectivity was validated against 10 gases. This work demonstrates the feasibility and superiority of robot-assisted construction of a customizable parent colorimetric sensor array to mitigate humidity interference in gas quantification.

Stabilizing Interlayer Repulsion in Layered Sodium-Ion Oxide Cathodes via Hierarchical Layer Modification.

Layered sodium-ion oxides hold considerable promise in achieving high-performance sodium-ion batteries. However, the notorious phase transformation during charging, attributed to increased O2-─O2- repulsion, results in substantial performance decay. Here, a hierarchical layer modification strategy is proposed to stabilize interlayer repulsion. During desodiation, migrated Li+ from the transition metal layer and anchored Ca2+ in sodium sites maintain the cationic content within the sodium layer. Meanwhile, partial oxygen substitution by fluorine and the involvement of oxygen in redox reactions increase the average valence of the oxygen layer. This sustained cation presence and elevated anion valence collectively mitigate increasing O2-─O2- repulsion during sodium extraction, enabling the Na0.61Ca0.05[Li0.1Ni0.23Mn0.67]O1.95F0.05 (NCLNMOF) cathode to retain a pure P2-type structure across a wide voltage range. Unexpected insights reveal the interplay between different doping elements: the robust Li─F bonds and Ca2+ steric effects suppressing Li+ loss. The NCLNMOF electrode exhibits 82.5% capacity retention after 1000 cycles and a high-rate capability of 94 mAh g-1 at 1600 mA g-1, demonstrating the efficacy of hierarchical layer modification for high-performance layered oxide cathodes.

Unveiling the molecular characteristics and antibacterial activity of tandem-repeat-type Galectin-8 in large yellow croaker (Larimichthys crocea).

Galectin-8 (Gal-8) is a versatile carbohydrate-binding protein with pivotal roles in immune regulation and cellular processes. This study introduces a novel galectin-8 protein, LcGal-8, from the large yellow croaker (Larimichthys crocea), showcasing typical characteristics of tandem-repeat-type galectins, including the absence of a signal peptide or transmembrane region and the presence of conserved sugar-binding motifs. Phylogenetic analysis reveals its conservation among fish species. Expression profiling indicates widespread distribution in immune tissues, particularly the spleen, implicating involvement in immune processes. The subcellular localization analysis reveals that LcGal-8 is present in both the cytoplasm and nucleus. Upon bacterial challenge, LcGal-8 is up-regulated in immune tissues, suggesting a role in host defense. Functional assays demonstrate that LcGal-8 can agglutinate gram-negative bacteria. The recombinant LcGal-8 protein agglutinates red blood cells from the large yellow croaker independently of Ca2⁺, however, this activity is inhibited by lipopolysaccharide (LPS) at 2.5 µg/mL. Fluorescence detection kits and scanning electron microscopy (SEM) confirm the agglutination and bactericidal effects of LcGal-8 against various gram-negative bacteria, including Vibrio harveyi, Aeromondaceae hydrophila, Aeromondaceae veronii, Pseudomonas plecoglossicida, Edwardsiella tarda. These findings contribute valuable insights into the genetic basis of disease resistance in the large yellow croaker and could support molecular breeding strategies to enhance disease resistance.

Baseline viral load and on-treatment hepatocellular carcinoma risk in chronic hepatitis B: A multinational cohort study.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) risk persists in chronic hepatitis B (CHB) patients despite antiviral therapy. The relationship between pre-treatment baseline hepatitis B virus (HBV) viral load and HCC risk during antiviral treatment remains uncertain. METHODS: This multinational cohort study aimed to investigate the association between baseline HBV viral load and on-treatment HCC risk in 20,826 noncirrhotic, hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with baseline HBV DNA levels ≥2,000 IU/mL (3.30 log10 IU/mL) who initiated entecavir or tenofovir treatment. The primary outcome was on-treatment HCC incidence, stratified by baseline HBV viral load as a categorical variable. RESULTS: In total, 663 patients developed HCC over a median follow-up of 4.1 years, with an incidence rate of 0.81 per 100 person-years (95% confidence interval [CI], 0.75-0.87). Baseline HBV viral load was significantly associated with HCC risk in a non-linear parabolic pattern, independent of other factors. Patients with baseline viral load between 6.00 and 7.00 log10 IU/mL had the highest on-treatment HCC risk (adjusted hazard ratio, 4.28; 95% CI, 2.15-8.52; P < .0001) compared to those with baseline viral load ≥8.00 log10 IU/mL, who exhibited the lowest HCC risk. CONCLUSION: Baseline viral load showed a significant, non-linear, parabolic association with HCC risk during antiviral treatment in noncirrhotic CHB patients. Early initiation of antiviral treatment based on HBV viral load may help prevent irreversible HCC risk accumulation in CHB patients.

Single-cell transcriptomics reveals writers of RNA modification-mediated immune microenvironment and cardiac resident Macro-MYL2 macrophages in heart failure.

BACKGROUND: Heart failure (HF), which is caused by cardiac overload and injury, is linked to significant mortality. Writers of RNA modification (WRMs) play a crucial role in the regulation of epigenetic processes involved in immune response and cardiovascular disease. However, the potential roles of these writers in the immunological milieu of HF remain unknown. METHODS: We comprehensively characterized the expressions of 28 WRMs using datasets GSE145154 and GSE141910 to map the cardiac immunological microenvironment in HF patients. Based on the expression of WRMs, the immunological cells in the datasets were scored. RESULTS: Single-cell transcriptomics analysis (GSE145154) revealed immunological dysregulation in HF as well as differential expression of WRMs in immunological cells from HF and non-HF (NHF) samples. WRM-scored immunological cells were positively correlated with the immunological response, and the high WRM score group exhibited elevated immunological cell infiltration. WRMs are involved in the differentiation of T cells and myeloid cells. WRM scores of T cell and myeloid cell subtypes were significantly reduced in the HF group compared to the NHF group. We identified a myogenesis-related resident macrophage population in the heart, Macro-MYL2, that was characterized by an increased expression of cardiomyocyte structural genes (MYL2, TNNI3, TNNC1, TCAP, and TNNT2) and was regulated by TRMT10C. Based on the WRM expression pattern, the transcriptomics data (GSE141910) identified two distinct clusters of HF samples, each with distinct functional enrichments and immunological characteristics. CONCLUSION: Our study demonstrated a significant relationship between the WRMs and immunological microenvironment in HF, as well as a novel resident macrophage population, Macro-MYL2, characterized by myogenesis. These results provide a novel perspective on the underlying mechanisms and therapeutic targets for HF. Further experiments are required to validate the regulation of WRMs and Macro-MYL2 macrophage subtype in the cardiac immunological milieu.

The role of Clec11a in bone construction and remodeling.

Bone is a dynamically active tissue whose health status is closely related to its construction and remodeling, and imbalances in bone homeostasis lead to a wide range of bone diseases. The sulfated glycoprotein C-type lectin structural domain family 11 member A (Clec11a) is a key factor in bone mass regulation that significantly promotes the osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts and stimulates chondrocyte proliferation, thereby promoting longitudinal bone growth. More importantly, Clec11a has high therapeutic potential for treating various bone diseases and can enhance the therapeutic effects of the parathyroid hormone against osteoporosis. Clec11a is also involved in the stress/adaptive response of bone to exercise via mechanical stimulation of the cation channel Pieoz1. Clec11a plays an important role in promoting bone health and preventing bone disease and may represent a new target and novel drug for bone disease treatment. Therefore, this review aims to explore the role and possible mechanisms of Clec11a in the skeletal system, evaluate its value as a potential therapeutic target against bone diseases, and provide new ideas and strategies for basic research on Clec11a and preventing and treating bone disease.

Ginsenoside RB1 Influences Macrophage-DPSC Interactions in Inflammatory Conditions.

INTRODUCTION AND AIMS: Unresolved inflammation and tissue destruction are supposed to underlie the failure of dental pulp repair. As crucial regulators of the injury response, dental pulp stem cells (DPSCs) play a key role in pulp tissue repair and regeneration. M2 macrophages have been demonstrated to induce osteogenic/odontogenic differentiation of DPSCs. Ginsenoside Rb1 (GRb1) is the major component of ginseng and manifested an anti-inflammatory role by promoting M1 macrophage polarised into M2 macrophage in inflammatory disease. However, whether GRb1 facilitates odontogenic differentiation of DPSCs via promoting M2 macrophage polarisation under inflammatory conditions has yet to be established. METHODS: Human monocyte leukemic cells (THP-1) differentiated macrophages were induced into M1 subsets and then treated with GRb1. After that, the conditioned medium was added to DPSCs. The cell co-cultured system was then subjected to odontogenic differentiation in osteogenic media. Effects of GRb1 on human dental pulp stem cells' (hDPSCs') osteogenic/odontogenic differentiation under inflammatory conditions were assessed by alkaline phosphatase (ALP) staining, Alizarin Red S (ARS) staining, and quantitative polymerase chain reaction testing. RESULTS: Results demonstrated that GRb1 could facilitate the polarisation of macrophages from the M1 subtype to the M2 subtype. Conditioned medium from GRb1 + M1 macrophages, in comparison with M1 macrophages, may markedly increase the gene expression of ALP, DSPP, and DMP1. Moreover, ALP and ARS staining uncovered that the osteogenic/odontogenic differentiation ability of hDPSCs was strengthened in the M1 + GRb1 co-culture group. CONCLUSIONS: GRb1 plays a crucial role in the inflammatory response and reparative dentine formation after dental pulp injury. Findings show that GRb1 modulates the interaction between macrophages and DPSCs during inflammation. The current study discusses modifications of deep caries therapy.

The Relationship Between Carotid Artery Stenosis and the Development of Open-Angle Glaucoma: A Long-term Cohort Study in Taiwan.

PURPOSES: To determine the relationship between carotid artery stenosis (CAS) and the development of open-angle glaucoma (OAG) in the Taiwanese population. METHODS: This retrospective cohort study was conducted using Chang Gung Research Database. Cox-proportional hazards model was applied to calculate the hazard ratio for OAG between CAS and the control cohort. RESULTS: Among 19,590 CAS patients, 17,238 had mild CAS (<50%), 1,895 had moderate CAS (50-69%), and 457 had severe CAS (≥70%). The CAS cohort had a higher proportion of several comorbidities. After adjusting for comorbidities, no significant difference in OAG development was found between CAS and control cohorts. Matching for key comorbidities, no significant differences in OAG incidence were found between matched cohorts (P = .869). Subdividing the matched CAS cohort by stenosis severity: mild (<50%), moderate (50-69%), and severe (≥70%), a statistically significantly lower OAG risk was observed in patients with mild CAS stenosis (HR: 1.12, 95% CI = 1.03-1.21, P = .006). Kaplan-Meier analysis revealed reduced OAG incidence in CAS patients who underwent surgical intervention, compared to the control cohort (P <.001). Subgroup analysis revealed that patients in the mild CAS stenosis group, those who underwent surgical intervention exhibited a reduced OAG risk (HR: 0.29, 95% CI = 0.15-0.58, P = .001). CONCLUSIONS: No statistically significant differences in OAG risk were observed between patients with CAS and the control cohort. The severity of CAS appears to influence OAG risk, with surgical intervention potentially offering protective effects, particularly in patients with mild CAS stenosis (<50%), suggesting that enhanced ocular perfusion post-surgery may act as a protective factor against OAG development.

Case report: intracranial lesions in a patient with anxiety and depression: tumor recurrence or radiation encephalopathy?

Purpose: Radiation encephalopathy (REP) is one of the most common complications of radiotherapy for malignant tumors of the head and neck. Symptoms usually appear months to years following radiotherapy, with headache, insomnia, and memory loss as the main clinical features. We report a patient who was admitted to the hospital with anxiety and depressive disorder and was eventually diagnosed with REP. Patients and methods: A 48-year-old patient who had undergone over 2 years of radiotherapy for nasopharyngeal carcinoma was admitted to the Department of Psychosomatic Medicine of our hospital because of recurrent fear, low mood, and waking up from dreams. Magnetic resonance imaging (MRI) revealed a mass in the left temporal lobe with a large peripheral edema. After multidisciplinary consultation, the possibility of tumor recurrence could not be excluded. Results: Resection of the lesioned brain tissue to obtain pathological tissue showed glial cell proliferation and small focal areas of degeneration and necrosis, which indicated that the lesions were inflammatory. Postoperative MRI showed no abnormal signal, and the patient's condition improved. Conclusion: Nasopharyngeal carcinoma patients with a history of radiotherapy and symptoms of increased intracranial pressure and neurological damage should be examined for REP. Furthermore, patients may experience anxiety and depressive disorders as a result of temporal lobe damage caused by REP.

Associations of asthma and psychiatric comorbidities on suicide mortality among community adolescents: A 20-year cohort study.

BACKGROUND: The role of psychiatric comorbidity as a confounder between asthma and subsequent suicide mortality in adolescents remained unclarified. METHODS: This study used a 20-year community-based cohort in Taiwan. Adolescents aged 11 to 16 from 123 schools were classified into three subgroups: current asthma (symptoms present in the past year), previous asthma (history of asthma but no symptoms in the past year), and no asthma. The mortality and medical care utilizations until the end of follow-up in 2015 were obtained. Cox proportional hazard and competing risk models were performed. Different adjustment models that included covariates of demographic status, allergy, cigarette smoking, psychiatric diagnoses, alcohol or substance misuse, and attention deficit and hyperactivity disorders were compared. RESULTS: During the follow-up, 285 out of 153,526 participants died from suicide. The crude hazard ratio for suicide was 1.95 (95 % CI=1.46∼2.60) in the current asthma subgroup and 2.01 (1.36∼2.97) in the previous asthma subgroup. The adjusted hazard ratios (aHR) attenuated to 1.67 (1.25∼2.24) and 1.72 (1.16∼2.54) respectively after further adjustment for all mental disorders, ADHD, substance, and alcohol use disorders. CONCLUSIONS: Our adjustment analyses stratified by different models highlight evidence of asthma as an independent risk factor that predicts suicide among adolescents. Depression and mental disorders were potential confounders and identifications of asthma and psychiatric disorders might help decrease suicide risk.

Carbon Quantum Dot-Functionalized Dermis-Derived Transparent Electronic Skin for Multimodal Human Motion Signal Monitoring and Construction of Self-Powered Triboelectric Nanogenerator.

Electronic skin (e-skin) is considered as a highly promising interface for human-computer interaction systems and wearable electronic devices. Through elaborate design and assembly of various materials, it possesses multiple characteristics similar to human skin, including remarkable flexibility, stretchability, sensitivity to temperature and humidity, biocompatibility, and efficient interfacial ion/electron transport capabilities. Here, we innovatively integrate multifunctional carbon quantum dots (CQDs), which exhibit conductivity, antibacterial properties, ultraviolet absorption, and fluorescence emission, with poly(acrylic acid) and glycerin (Gly) into a three-dimensional network structure of natural goatskin collagen fibers. Through a top-down design strategy enhanced by hydrogen bond reconstruction, we successfully fabricated a novel transparent e-skin (PAC-eSkin). This e-skin exhibited significant tensile properties (4.94 MPa of tensile strength and 263.42% of a maximum breaking elongation), while also possessing Young's modulus similar to human skin (2.32 MPa). It is noteworthy that the functionalized CQDs used was derived from discarded goat hair, and the addition of Gly gave PAC-eSkin excellent antifreezing and moisturizing properties. Due to the presence of ultrasmall CQDs, which creates efficient ion/electron transport channels within PAC-eSkin, it could rapidly sense human motion and physiological signals (with a gauge factor (GF) of 1.88). Furthermore, PAC-eSkin had the potential to replace traditional electrode patches for real-time monitoring of electrocardiogram, electromyogram, and electrooculogram signals, with a higher SNR (signal-to-noise ratio) of 25.1 dB. Additionally, the customizable size and shape of PAC-eSkin offer vast possibilities for the construction of single-electrode triboelectric nanogenerator systems. We have reason to believe that the design and development of this transparent e-skin based on CQDs-functionalized dermal collagen matrices can pave a new way for innovations in human-computer interaction interfaces and their sensing application in diverse scenarios.

Ginsenoside Rb1 ameliorates apical periodontitis via suppressing macrophage pyroptosis.

OBJECTIVES: The objectives of current study were to investigate the role and related mechanism of Ginsenoside Rb1 (GRb1) on regulating apical periodontitis (AP) prognosis. MATERIALS AND METHODS: Clinical specimens were used to determine the involvement of calcium overload-induced macrophage pyroptosis in periapical tissues. Next, a calcium ion-chelating agent (BAPTA-AM) was applied to detect the suppression of intracellular calcium overload in macrophage pyroptosis. Then, network pharmacology, western blot (WB) analysis, and Fluo-4 calcium assay were conducted to explore the role of GRb1 on intracellular calcium overload. To gain a better understanding of GRb1 in calcium overload-induced macrophage pyroptosis linked AP, GRb1-treated AP models were established. RESULTS: We discovered clinically and experimentally that calcium overload-dependent macrophage pyroptosis is involved in AP pathogenesis, and reducing calcium overload greatly decreased macrophage pyroptosis in an AP cell model. Next, based on GRb1's inhibitory role in aberrant intracellular calcium accumulation, we discovered that GRb1 alleviates AP by suppressing calcium-dependent macrophage pyroptosis in both in vitro and in vivo models. CONCLUSIONS: GRb1 is an effective therapeutic strategy to rescue the periapical tissues from inflammation due to its anti-pyroptosis function. Thus, the present study supports further investigation of GRb1 as an adjuvant therapy for AP.

Dynamic Evolution of Copper Nanowires during CO2 Reduction Probed by Operando Electrochemical 4D-STEM and X-ray Spectroscopy.

Nanowires have emerged as an important family of one-dimensional (1D) nanomaterials owing to their exceptional optical, electrical, and chemical properties. In particular, Cu nanowires (NWs) show promising applications in catalyzing the challenging electrochemical CO2 reduction reaction (CO2RR) to valuable chemical fuels. Despite early reports showing morphological changes of Cu NWs after CO2RR processes, their structural evolution and the resulting exact nature of active Cu sites remain largely elusive, which calls for the development of multimodal operando time-resolved nm-scale methods. Here, we report that well-defined 1D copper nanowires, with a diameter of around 30 nm, have a metallic 5-fold twinned Cu core and around 4 nm Cu2O shell. Operando electrochemical liquid-cell scanning transmission electron microscopy (EC-STEM) showed that as-synthesized Cu@Cu2O NWs experienced electroreduction of surface Cu2O to disordered (spongy) metallic Cu shell (Cu@CuS NWs) under CO2RR relevant conditions. Cu@CuS NWs further underwent a CO-driven Cu migration leading to a complete evolution to polycrystalline metallic Cu nanograins. Operando electrochemical four-dimensional (4D) STEM in liquid, assisted by machine learning, interrogates the complex structures of Cu nanograin boundaries. Correlative operando synchrotron-based high-energy-resolution X-ray absorption spectroscopy unambiguously probes the electroreduction of Cu@Cu2O to fully metallic Cu nanograins followed by partial reoxidation of surface Cu during postelectrolysis air exposure. This study shows that Cu nanowires evolve into completely different metallic Cu nanograin structures supporting the operando (operating) active sites for the CO2RR.

A two-pronged approach to inhibit ferroptosis of MSCs caused by the iron overload in postmenopausal osteoporosis and promote osseointegration of titanium implant.

Postmenopausal osteoporosis (PMOP) is a prevalent condition among elderly women. After menopause, women exhibit decreased iron excretion, which is prone to osteoporosis. To design a specific titanium implant for PMOP, we first analyze miRNAs and DNA characteristics of postmenopausal patients with and without osteoporosis. The results indicate that iron overload disrupts iron homeostasis in the pathogenesis of PMOP. Further experiments confirm that iron overload can cause lipid peroxidation and ferroptosis of MSCs, thus breaking bone homeostasis. Based on the findings above, we have designed a novel Ti implant coated with nanospheres of caffeic acid (CA) and deferoxamine (DFO). CA can bind on the Ti surface through the two adjacent phenolic hydroxyls and polymerize into polycaffeic acid (PCA) dimer, as well as the PCA nanospheres with the repetitive 1,4-benzodioxan units. DFO was grafted with PCA through borate ester bonds. The experimental results showed that modified Ti can inhibit the ferroptosis of MSCs in the pathological environment of PMOP and promote osseointegration in two main ways. Firstly, DFO was released under high oxidative stress, chelating with excess iron and decreasing the labile iron pool in MSCs. Meanwhile, CA and DFO activated the KEAP1/NRF2/HMOX1 pathway in MSCs and reduced the level of intracellular lipid peroxidation. So, the ferroptosis of MSCs is inhibited by promoting the SLC7A11/GSH/GPX4 pathway. Furthermore, the remained CA coating on the Ti surface could reduce the extracellular oxidative stress and glutathione level. This study offers a novel inspiration for the specific design of Ti implants in the treatment of PMOP.

Effect and mechanism of Qingre Huashi decoction on drug-resistant Helicobacter pylori.

BACKGROUND: Helicobacter pylori (HP), the most common pathogenic microorganism in the stomach, can induce inflammatory reactions in the gastric mucosa, causing chronic gastritis and even gastric cancer. HP infection affects over 4.4 billion people globally, with a worldwide infection rate of up to 50%. The multidrug resistance of HP poses a serious challenge to eradication. It has been de-monstrated that compared to bismuth quadruple therapy, Qingre Huashi decoction (QHD) combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions; in addition, QHD can directly inhibit and kill HP in vitro. AIM: To explore the effect and mechanism of QHD on clinically multidrug-resistant and strong biofilm-forming HP. METHODS: In this study, 12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected patients. In vitro, the minimum inhibitory concentration (MIC) values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining, respectively. The most robust biofilm-forming strain of HP was selected, and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm formation. This assessment was performed using agar dilution, E-test, killing dynamics, and transmission electron microscopy (TEM). The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm formation. Crystalline violet method, scanning electron microscopy, laser confocal scanning microscopy, and (p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP strains. The effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain reaction. Non-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD groups. RESULTS: HP could form biofilms of different degrees in vitro, and the intensity of formation was associated with the drug resistance of the strain. QHD had strong bacteriostatic and bactericidal effects on HP, with MICs of 32-64 mg/mL. QHD could inhibit the biofilm formation of the strong biofilm-forming HP strains, disrupt the biofilm structure, lower the accumulation of (p)ppGpp, decrease the expression of biofilm-related genes including LuxS, Spot, glup (HP1174), NapA, and CagE, and reduce the expression of efflux pump-related genes such as HP0605, HP0971, HP1327, and HP1489. Based on metabolomic analysis, QHD induced oxidative stress in HP, enhanced metabolism, and potentially inhibited relevant signaling pathways by upregulating adenosine monophosphate (AMP), thereby affecting HP growth, metabolism, and protein synthesis. CONCLUSION: QHD exerts bacteriostatic and bactericidal effects on HP, and reduces HP drug resistance by inhibiting HP biofilm formation, destroying its biofilm structure, inhibiting the expression of biofilm-related genes and efflux pump-related genes, enhancing HP metabolism, and activating AMP in HP.

Metabolic syndrome and risk of subclinical hypothyroidism: a systematic review and meta-analysis.

Background: Subclinical hypothyroidism (SCH) is a common endocrine subclinical disorder, the main adverse consequences of which are the development of clinical hypothyroidism and the promotion of ischemic heart disease. Metabolic syndrome (MetS) is a collection of metabolic problems. The goal of this meta-analysis was to evaluate the relationship between MetS and SCH. Methods: Suitable publications were identified using PubMed, Embase, and the Cochrane Library. The meta-analysis included only studies in English that reported odds ratio (OR) data for MetS and SCH. Two researchers combined data using a random-effects model. OR and 95% confidence intervals (CIs) were used to present the results. Results: MetS was associated with an elevated risk of developing SCH (OR 2.56, 95% CI 1.44-4.55). However, the individual components of MetS were not associated with the risk of SCH. Subgroup analysis revealed that different definitions of MetS had varying effects on SCH. Sensitivity analysis confirmed that our results were robust. Conclusions: This meta-analysis indicates that patients with MetS have an increased risk of SCH, while there is no significant association between the five individual components of MetS and the risk of SCH. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023454415.