Impact of Acute Short-term Hypobaric Hypoxia on Anterior Chamber Geometry.

PRCIS: Hypobaric hypoxia, the major environmental factor at high altitudes, has been observed to induce pupil miosis and widening of the anterior chamber angle. This environment may be safe for individuals with narrow angle and deserves further study. PURPOSE: This study aimed to quantify anterior chamber biometric parameters before and after acute short-term, effortless exposure to hypobaric hypoxia (HH) in healthy lowlanders using swept-source anterior segment optical coherence tomography (SS AS-OCT). METHODS: This prospective study included 25 healthy young lowlanders (50 eyes) who underwent SS AS-OCT measurements and intraocular pressure (IOP) assessments under baseline sea-level conditions (T1).They were then passively exposed to simulated 4000 m above sea level for 3 hours and underwent Acute mountain sickness (AMS) symptoms evaluation and IOP measurement after 2-hours exposure to HH (T2).Repeat SS AS-OCT measurements and IOP assessments were taken within 15 minutes after leaving the hypobaric chamber (T3). Anterior segment parameters including anterior chamber depth (ACD),lens vault (LV),angle opening distance (AOD500), trabecular-iris space area (TISA500), angle recess area (ARA500) at 500 µm from the scleral spur, iris curvature (IC), iris volume (IV), pupil diameter (PD), and central corneal thickness (CCT) were obtained through SS AS-OCT. These repeated measurements were compared using linear mixed model analysis. RESULTS: In comparison to sea level, both IOP (16.4±3.4 vs. 14.9±2.4 mm Hg, P=0.029) and PD (5.36±0.77 vs. 4.78±0.89 mm, P=0.001) significantly decreased after exposure to HH. Significant post-HH changes (Mean difference (95% CI)) were observed in AOD500 (0.129 (0.006, 0.252), P=0.04), TISA500 (0.059 (0.008, 0.11), P=0.025), ARA500 (0.074 (0.008, 0.141), P=0.029), IV (1.623 (0.092, 3.154), P=0.038), and IC (-0.073 (-0.146, 0.001), P=0.047), while CCT, ACD, and LV remained stable. After adjusting for age, post-HH variations in AOD500 (Beta=0.553, 95% CI: 0.001, 1.105, P=0.048) and TISA500 (Beta=0.256, 95% CI: 0.02, 0.492, P=0.034) were associated with decreased IC but were not related to lowered arterial oxygen pressure or IV increase per millimeter of pupil miosis (IV/PD). These differences in anterior segment parameters were neither correlated with differences in IOP nor AMS. CONCLUSION: After short-term, effortless exposure to hypobaric hypoxia, pupil miosis occurred with widening of the anterior chamber angle and decreased IC. These changes in anterior chamber angle parameters were associated with decreased IC but did not correlate with the post-hypobaric variations in IV/PD, IOP, or AMS.

Analysis of recurrence factors after balloon compression for trigeminal neuralgia and the relationship between pear-shaped balloon and guidewire path.

BACKGROUND: Percutaneous balloon compression (PBC) is widely used to treat trigeminal neuralgia due to its significant efficacy and low treatment cost. However, there is considerable variation in postoperative pain recurrence among patients. Currently, the factors influencing pain recurrence after PBC are under discussion. This study aims to explore the impact of individual patient parameters and surgical parameters on postoperative pain recurrence following PBC. The goal is to provide clinicians with a reference for preoperative assessment of pain recurrence risk and to offer insights for effectively intervening in controllable influencing parameters. METHODS: A analysis was conducted on 114 patients who underwent PBC in the Department of Neurosurgery at Hebei General Hospital. Univariate Kaplan-Meier analysis and multivariate Cox regression analysis were performed on the general and surgical data of the patients to identify factors potentially associated with postoperative pain recurrence. RESULTS: The results of the multivariate Cox regression analysis showed that a history of hypertension, MRI indicating trigeminal nerve compression and a non-ideal pear-shaped balloon were statistically significant factors for pain recurrence after PBC. Additionally, the guidewire path during the procedure had a statistically significant impact on the rate of achieving a pear-shaped balloon (P<0.05). CONCLUSION: A history of hypertension, MRI indicating trigeminal nerve compression and a non-ideal pear-shaped balloon shape are independent risk factors for pain recurrence after PBC. Additionally, to avoid pain recurrence due to an unfavorable balloon shape, it is recommended to use 3D-slicer for preoperative guidewire path simulation and 3D reconstruction of Meckel's cavity.

Association between initial diquat plasma concentration, severity index and in-hospital mortality in patients with acute diquat poisoning: a retrospective cohort study.

BACKGROUND: Since 2016, diquat has replaced paraquat in China, resulting in increased diquat poisoning cases. However, understanding of diquat poisoning is still limited. This study aimed to investigate the relationship between initial diquat plasma concentration, severity index, and in-hospital mortality in acute diquat poisoning cases. METHODS: This retrospective cohort study, conducted from January 2016 to July 2023 in a tertiary care hospital, used univariate logistic regression to examine the link between the initial diquat plasma concentration, severity index, and in-hospital mortality in acute diquat poisoned patients. A receiver operating characteristic curve assessed the predictive value of these parameters for prognosis. RESULTS: Among the 87 participants, the median age was 32 years, 35 (40.2%) were female. The overall mortality rate was 37.9%. Logistic regression analysis revealed that the initial diquat plasma concentration and severity index were associated with increased in-hospital mortality. These factors also effectively predicted the prognosis of acute diquat poisoning, with an area under the receiver operating characteristic curve of 0.851 and an optimal diquat concentration threshold of 2.25 mg/L (sensitivity 90.9%, specificity 74.1%, P < 0.05) and an area under the receiver operating characteristic curve of 0.845 with an optimal cut-off value for the sevity index of 9.1 mg/L*min (sensitivity 97%, specificity 74.1%, P < 0.05). DISCUSSION: Our results are limited by the retrospective design of this study. However, if validated, these results could impact management strategies, especially in East Asia. Further research is needed due to potential confounding factors. CONCLUSIONS: The findings suggest that a higher initial plasma concentration and severity index in patients with acute diquat poisoning were correlated with higher in-hospital mortality. Prospective validation will confirm the predicative value of these findings.

Identification of Potential Therapeutics for Infantile Hemangioma via in silico Investigation and in vitro Validation.

Introduction: Infantile Hemangioma (IH) is a prevalent benign vascular tumor affecting approximately 5-10% of infants. Its underlying pathogenesis remains enigmatic, and current therapeutic approaches show limited effectiveness. Our study aimed to discover potential IH-associated therapeutics through a transcriptomic, computational drug repurposing methodology. Methods: Utilizing the IH-specific dataset GSE127487 from the Gene Expression Omnibus, we identified differentially expressed genes (DEGs) and conducted weighted gene coexpression network analysis (WGCNA). Subsequently, a protein-protein interaction (PPI) network was constructed to obtain the top 100 hub genes. Drug candidates were sourced from the Connectivity Map (CMap) and Comparative Toxicogenomics Database (CTD). Results: Our analysis revealed 1203 DEGs and a significant module of 1780 mRNAs strongly correlated with IH. These genes were primarily enriched in the PI3K/AKT/MTOR, RAS/MAPK, and CGMP/PKG signaling pathway. After creating a PPI network of overlapping genes, we filtered out the top 100 hub genes. Ultimately, 44 non-toxic drugs were identified through the CMap and CTD databases. Twelve molecular-targeting agents (belinostat, chir 99021, dasatinib, entinostat, panobinostat, sirolimus, sorafenib, sunitinib, thalidomide, U 0126, vorinostat, and wortmannin) may be potential candidates for IH therapy. Moreover, in vitro experiments demonstrated that entinostat, sorafenib, dasatinib, and sirolimus restricted the proliferation and migration and initiated apoptosis in HemEC cells, thereby underscoring their potential therapeutic value. Conclusion: Our investigation revealed that the pathogenic mechanism underlying IH might be closely associated with the PI3K/AKT/MTOR, RAS/MAPK, and CGMP/PKG signaling pathways. Furthermore, we identified twelve molecular-targeting agents among the predicted drugs that show promise as therapeutic candidates for IH.

Transcriptomic analysis used to discover potential therapeutics for Infantile Hemangioma (IH). Key IH-related pathways: PI3K/AKT/MTOR, RAS/MAPK, and CGMP/PKG signaling identified. Identified 44 non-toxic drugs as potential IH therapies via CMap and CTD. Twelve molecular agents show potential as IH therapy candidates. In vitro studies confirmed entinostat, sorafenib, dasatinib, and sirolimus inhibit HemEC cell proliferation and induce apoptosis.

Natural agents derived Pickering emulsion enabled by silica nanoparticles with enhanced antibacterial activity against drug-resistant bacteria.

The emergence of antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) has become a global health challenge due to the overuse of antibiotics. Natural substances including enzymes and essential oils have shown great potential as alternative treatment options. However, the combinational use of these natural agents remains challenging due to the denaturation of enzymes upon direct contact with oil. In this study, we report the design of a Pickering emulsion containing two natural antibacterial agents, lysozyme and tea tree oil, stabilized by fractal silica nanoparticles. In this design, the enzyme activity is kept and the volatility problem of tea tree oil is mitigated. Due to synergistic bacterial cell wall digestion and membrane disruption functions, potent bactericidal efficacy in vitro against drug-resistant bacteria is achieved. The therapeutic potential is further demonstrated in a wound healing model with drug-resistant bacteria infection, better than a synthetic antibiotic, Ampicillin. This study opens new avenues for the development of natural product-based antimicrobial treatments with promising application potential.

Associations of static and dynamic iris parameters in healthy Chinese individuals: the Handan Eye Study.

PURPOSE: To determine the associations between the demographic factors (age and sex) and physiological dynamic iris changes and explore the associated factors for iris cross-sectional area (IA) change in healthy Chinese individuals. METHODS: This cross-sectional study included individuals aged ≥40 years with an open angle and underwent anterior segment optical coherence tomography under light and dark conditions from the follow-up cohort of the Handan Eye Study. Ocular data from the right eye were analyzed. The Pearson correlation coefficient was used to assess the relationship between age and iris parameters, including iris thickness (IT), IA, and iris curvature (IC), as well as the pupil diameter (PD) in the dark, and their changes from light to dark conditions. Linear regression analysis was performed to identify the potential factors associated with IA change. RESULTS: The final analysis included 465 healthy individuals. PD in dark, IA change and PD change decreased with age (P < 0.001), whereas IC increased with age (P < 0.001). IT and IT change were smaller, and IC was larger in women than that in men (P = 0.021, 0.007, and 0.010, respectively). Older age (P = 0.041), larger lens thickness (P = 0.013), larger IC change (P < 0.001), and smaller PD change (P < 0.001) were significantly associated with a smaller IA change. CONCLUSIONS: Our study demonstrated the associations of static and dynamic iris parameters in healthy Chinese individuals. The findings provided a possible explanation for the higher prevalence of primary angle closure disease in elderly and female populations.

Drug-drug interactions of simnotrelvir/ritonavir: an open-lable, fixed-sequence, two-period clinical trial.

OBJECTIVES: Simnotrelvir is a small molecule highly specific 3C-like protease inhibitor for anti-SARS-CoV-2 and was approved as a combination drug with ritonavir (simnotrelvir/ritonavir) in China. Simnotrelvir is a substrate of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), and a weak inhibitor of CYP3A. Ritonavir is a substrate and inhibitor of CYP3A and an inhibitor of P-gp. Hence, the drug-drug interaction (DDI) potential of simnotrelvir/ritonavir should be investigated. METHODS: This DDI study was an open-label, fixed-sequence, two-period Phase I clinical trial in Chinese healthy adult subjects, divided into 3 cohorts, including simnotrelvir/ritonavir co-administrated with a strong CYP3A and P-gp inhibitor (itraconazole) and inducer (rifampicin), and with a specific CYP3A substrate (midazolam). RESULTS: The results demonstrated that compared to administration of simnotrelvir/ritonavir alone, the co-administration with itraconazole increased the geometric least-square mean ratio (GMR) of the expose (AUC0-t) of simnotrelvir by 25% (GMR 125%, 90% confidence interval (CI) 114% - 137%), whereas co-administration with rifampicin significantly decreased the AUC0-t of simnotrelvir by 81.5% (GMR 18.5%, 90% CI 16.4% - 20.9%). Notably, simnotrelvir/ritonavir increased the AUC0-t of midazolam by 16.69-fold (GMR 1769%, 90% CI 1551% - 2018%). The co-administration of simnotrelvir/ritonavir and rifampicin caused the increased amount and severity of treatment-emergent adverse events, especially hepatotoxicity. CONCLUSIONS: The co-administration of simnotrelvir/ritonavir with CYP3A and P-gp inhibitors can be safely used, while the co-administration with CYP3A and P-gp strong inducer should be avoided to minimize the risk of under-exposure. Co-administration of midazolam with simnotrelvir/ritonavir increased systemic exposure of midazolam. GOV IDENTIFIER: NCT05665647.

A high-order time-delay difference estimation method for signal enhancement in the distorted towed hydrophone array.

In passive sonar systems, deviations from an ideal linear configuration can significantly impair the beamforming performance of towed hydrophone arrays. This paper presents a method aimed at improving the underwater acoustic signals in the presence of array distortion. The method is centered on a high-order time-delay difference estimation technique utilizing time-frequency autofocus. Initially, a detailed signal model is established that captures the distinctive characteristics of distorted arrays. Subsequently, an algorithm is introduced for high-order time-delay difference estimation to enhance signal fidelity by leveraging phase information within narrowband components originating from incidental acoustic sources. Additionally, a quality metric to evaluate these components is introduced, facilitating the practical implementation of the method. The effectiveness of the proposed approach is validated through both simulation and experimental results, demonstrating its superiority over existing techniques. Importantly, this method does not require prior knowledge of the distortion pattern, making it adaptable to various non-linear array configurations.

Comparing 24-hour IOP fluctuation slope curve between newly diagnosed ocular hypertension and primary open-angle glaucoma.

OBJECTIVE: To compare the 24-hour intraocular pressure (IOP) fluctuation slope curve between newly diagnosed patients with ocular hypertension (OHT) and primary open-angle glaucoma (POAG). METHODS AND ANALYSIS: Newly diagnosed and untreated OHT and POAG patients who underwent 24-hour IOP monitoring were consecutively enrolled in the study. IOP measurements were taken every 2 hours from 8:00 to 6:00 hours the following day using an iCare PRO tonometer. Patients maintained their daily routines, with IOP measured in a seated position during the day and supine at night. The 24-hour IOP fluctuation indices, including peak, trough and overall fluctuation, were calculated. Differences in the 24-hour IOP fluctuation slope curves over time between groups were analysed using a generalised additive mixed model. RESULTS: 46 patients with OHT and 41 with POAG were included. From 2:00 to 10:00 hours, mean IOP increased by 0.69 mm Hg every 2 hours in the POAG group (p<0.0001) and by 0.40 mm Hg in the OHT group (p<0.0001). After 10:00, the IOP showed a downward trend, decreasing by 0.31 mm Hg in the POAG group (p<0.0001) and by 0.17 mm Hg in the OHT group (p=0.0003) every 2 hours. The rate of slope change in the upward phase differed significantly between the groups (0.30 mm Hg per 2 hours; p=0.02), as did the rate in the downward phase (0.14 mm Hg per 2 hours; p for interaction=0.04). Multivariate models showed that each 1 mm Hg increase in circadian and diurnal IOP fluctuation was associated with a 27% and 21% higher likelihood of POAG presence, respectively. CONCLUSION: The 24-hour IOP slope curve differed between POAG and OHT, with a steeper slope observed in the POAG group. However, the study is limited by potential confounding factors, reliance on a single 24-hour measurement period and the need for further longitudinal studies to validate these findings.

The effectiveness of the DNA-V program on reducing anxiety among Chinese adolescents: Outcomes of the face-to-face and web-based versions.

Many studies have indicated an alarming prevalence of anxiety among Chinese adolescents, highlighting the critical need for prevention protocols. DNA-V (Discoverer, Noticer, Advisor-Values model) is an adapted version of Acceptance and Commitment Therapy designed to prevent mental health problems in adolescents. This study investigated the effects and underlying mechanisms of DNA-V. The DNA-V prevention program was culturally adapted and optimized in both content and form specifically for Chinese adolescents, with the aim of reducing anxiety levels. A total of 139 participants (59 females) from six eighth-grade classes at an average middle school in Beijing were randomly assigned to one of three groups consisting of the DNA-V face-to-face group (two classes), the DNA-V web-based group (two classes), or the active control group (two classes). Adolescents' anxiety and cognitive fusion were measured before (Time 1), immediately after (Time 2), and 2 months after (Time 3) the program using the Chinese Secondary School Students Anxiety Scale (CSSSAS) and Cognitive Fusion Questionnaire (CFQ). Results showed that in the DNA-V face-to-face group, the anxiety score at Time 3 was significantly lower than the scores at Time 1 (p < .001, Cohen's drm = 0.56) and Time 2 (p = .043, Cohen's drm = 0.24). The cognitive fusion score at Time 3 was significantly lower than the scores at Time 1 (p = .001, Cohen's drm = 0.51) and Time 2 (p = .003, Cohen's drm = 0.37). The results of the study suggest that the DNA-V prevention program could serve as an effective tool for reducing anxiety in adolescents.

Metabolomics combined with physiology reveal how white clover (Trifolium repens L.) respond to 6PPD stress.

As a ubiquitous tire antioxidant, N-(1,3-Dimethyl-butyl)-N'-phenyl-p-phenylene- diamine (6PPD) exists widely in various environmental media and has been detected at high levels in the environment. However, the effects of 6PPD on plants are still poorly understood. In this study, a hydroponic experiment was carried out to investigate the response of white clover (Trifolium repens L.) stressed by 6PPD on physiology and metabolomics. The results indicated that the length of stem and root, as well as biomass were significantly reduced after 500 µg L-1 6PPD treatment. Photosynthetic performances including photosynthetic rate (Pn), stomatal conductance (Gs), intercellular CO2 concentration (Ci), transpiration rate (Tr) and chlorophyll content of leaves decreased in all treatments except 500 µg L-1 of 6PPD. The malondialdehyde (MDA) content in the shoot of white clover increased by 66.33 % when exposed to 500 µg L-1 of 6PPD compared to control group (CK). Hydrogen peroxide and superoxide anion presented a U-shape trend and began to increase at 500 µg L-1. Besides, peroxidase and catalase significantly decreased compared to CK after exposure to 500 µg L-1. Metabolic analysis of clover showed that 6PPD treatment induced changes in 10 metabolic pathways of white clover. Metabolites were significantly down-regulated after exposure to 500 µg L-1 in shoot, while significantly down-regulated in all treatment groups except 500 µg L-1 in root. These findings may provide a novel perspective for phytotoxicity assessment and phytoremediation of 6PPD.

A Cyclometalated Iridium(III) Complex Exerts High Anticancer Efficacy via Fatty Acid Beta-Oxidation Inhibition and Sphingolipid Metabolism Reprogramming.

Given the extensive role of lipids in cancer development, there is substantial clinical interest in developing therapies that target lipid metabolism. In this study, we identified one cyclometalated iridium complex (Ir2) that exhibits potent antiproliferation activity in MIA PaCa-2 cells by regulating fatty acid metabolism and sphingolipid metabolism simultaneously. Ir2 also efficiently overcomes cisplatin resistance in vitro. Satisfyingly, the generated Ir2@F127 carriers, as a temperature-sensitive in situ gelling system of Ir2, showed effective cancer treatment with minimal side effects in an in vivo xenograft study. To the best of our knowledge, Ir2 is the first reported cyclometalated iridium complex that exerts anticancer activity in MIA PaCa-2 cells by intervening in lipid metabolism, which provides an alternative pathway for the anticancer mechanism of cyclometalated iridium complexes.

Factors influencing the dissolution rate of radon gas in water.

Measurements of radon (222Rn) in water are widely utilized across various disciplines, including technology, medicine, exploration, and ecological preservation. For accurate radon measurements in water, the availability of a standardized radon solution is essential. Researchers have predominantly concentrated on the radon concentration in water (RCW) once radon distribution equilibrium is achieved, rather than the rate of radon dissolution prior to equilibrium, in the development of standard radon solutions. This makes the preparation speed of the calibration standards radon solution slow, which seriously restricts the research and development of the standard device. The purpose of this paper is to investigate the correlation between the rate of radon dissolution and both the concentration of gaseous radon and the stirring speed. Four conclusions have been derived through univariate analysis. ➀ The radon concentration in water (RCW) increases with the duration of radon dissolution, eventually reaching a state of equilibrium. ➁ The increase in gas radon concentration correlates with a simultaneous rise in the rate of radon dissolution, while the time required for radon distribution equilibrium remains constant. ➂ The augmentation of the stirring speed enhances the rate of radon dissolution, Concurrently reducing the time needed for RCW to reach equilibrium.➃ When the stirring speed is excessively high, it results in substantial fluctuations in both RCW and the rate of radon dissolution. Consequently, when employing this method for the preparation of radon solutions, it is advisable to regulate the duration of radon dissolution to 30 min at a rate of 380 rad/min and 10 min at a rate of 480 rad/min. This regulation ensures the attainment of precise concentrations. Under conditions of environmental stability, manipulation of gas radon concentration alone proves sufficient for adjusting RCW . These empirical findings furnish a robust foundation for the efficient preparation of standardized radon solutions and the requisite apparatus, essential for the calibration and accuracy of radon measurement instruments.

Significance of longitudinal Epstein-Barr virus DNA combined with multipoint tumor response for dynamic risk stratification and treatment adaptation in nasopharyngeal carcinoma.

Dynamic therapy response is strongly associated with cancer outcomes. This study aimed to evaluate the significance of longitudinal Epstein-Barr virus (EBV) DNA and radiological tumor regression in risk stratification and response-adaptive treatment in locally-advanced nasopharyngeal carcinoma (LA-NPC). In total, 1,312 patients from two centers were assigned to the training and validation cohorts. Based on the multipoint examination of EBV-DNA and tumor response, four post-induction chemotherapy, four mid-radiotherapy, and four post-radiotherapy subgroups were established. Then seven phenotypes were further generated according to different permutations and combinations. These phenotypes were subsequently congregated into four response clusters, which reflect distinct biological treatment responses. The four response clusters correlated with an evident 5-year progression-free survival in both the training and external validation cohorts (5-year: training cohort 91.1%, 82.8%, 30.6%, and 10.0%; external validation 94.4%, 55.6%, 40.0%, and 12.7%) had superior prognostic performance compared to TNM staging and nomogram model (concordance index: training cohort-0.825 vs. 0.603 vs. 0.756 and external validation-0.834 vs. 0.606 vs. 0.789). Importantly, the response clusters exhibited an excellent capability in selecting candidates who can benefit from adjuvant chemotherapy. In conclusion, risk stratification based on the dynamic assessment of both radiological and biological responses can significantly enhance prognostic insights and shed light on individualized treatment modifications in LA-NPCs.

Simultaneous co-assembly of collagen and glycosaminoglycans to build a biomimetic extracellular matrix for bone regeneration.

Glycosaminoglycans (GAGs), also known as shape modules, are considered junctions that help define the shape of collagen matrix and further promote mineralization during osteogenesis. Many attempts have been made to immobilize GAGs on assembled collagen to modify the latter's surface state. However, it remains unclear how GAGs spontaneously identify collagen molecules during fibrillogenesis in vivo. Understanding the relationship between GAGs and collagen from both the bone physiology and materials science perspectives is of fundamental interest. Here, we introduced hyaluronic acid (HA, a main member of GAGs) during collagen self-assembly, in a process called modification cooperating with self-assembly (MCS). The molecular docking and morphological studies revealed that HA can help define collagen monomer deposition and thus promote fibrillogenesis through steric hindrance or by directly forming hydrogen bonds. Meanwhile, HA acts as a templating chaperone (TC) to increase the local mineral concentration within intrafibrillar channels but does not initiate nucleation, thus improving the crystallinity of formed apatite. The scaffolds synthesized through MCS model significantly improved the physicochemical stability and mechanical strength of collagen-based scaffolds. The optimized scaffolds promoted in-situ osteogenesis by stimulating the osteogenic differentiation of bone mesenchymal stem cells, either in an osteogenic medium, or after implantation into critical calvarial defects. This study provides novel insights towards evolving engineering scaffolds from inert supports to functional substitutes.

Wolbachia and mosquitoes: Exploring transmission modes and coevolutionary dynamics in Shandong Province, China.

Vector-borne diseases leave a large footprint on global health. Notable culprits include West Nile virus (WNV), St. Louis encephalitis virus (SLEV), and Japanese encephalitis virus (JEV), all transmitted by Culex mosquitoes. Chemical insecticides have been widely used to reduce the spread of mosquito-borne diseases. Still, mosquitoes are becoming more and more resistant to most chemical insecticides which cause particular harm to the ecology. Wolbachia belongs to the family Ehrlichiaceae in the order Rickettsiales and is a matrilineally inherited endosymbiont present in 60% of insects in nature. Wolbachia is capable of inducing a wide range of reproductive abnormalities in its hosts, such as cytoplasmic incompatibility, and can alter mosquito resistance to pathogen infection. Wolbachia has been proposed as a biological alternative to chemical vector control, and specific research progress and effectiveness have been achieved. Despite the importance of Wolbachia, this strategy has not been tested in Culex pipiens pallens, the most prevalent mosquito species in Shandong Province, China. Little is known about how the mass release of Wolbachia-infected mosquitoes may impact the genetic structure of Culex pipiens pallens, and how the symbiotic bacterium Wolbachia interacts with mitochondria during host mosquito transmission. Based on the population genetic structure of Culex pipiens pallens in Shandong Province, this study investigated the infection rate and infection type of Wolbachia in Shandong Province and jointly analysed the evolutionary relationship between the host mosquito and the symbiotic bacterium Wolbachia. Our study showed that Wolbachia naturally infected by Culex pipiens pallens in Shandong Province was less homologous to Wolbachia infected by Aedes albopictus released from mosquito factory in Guangzhou. Our results also show that Culex pipiens pallens is undergoing demographic expansion in Shandong Province. The overall Wolbachia infection rate of Culex pipiens pallens was 92.8%, and a total of 15 WSP haplotypes were detected. We found that the genetic diversity of Wolbachia was low in Culex pipiens pallens from Shandong Province, and the mosquitoes were infected only with type B Wolbachia. Visualizing the relationship between Culex pipiens pallens and Wolbachia using a tanglegram revealed patterns of widespread associations. A specific coevolutionary relationship exists between the host mosquito and Wolbachia. Knowledge of this mosquito-Wolbachia relationship will provide essential scientific information required for Wolbachia-based vector control approaches in Shandong Province and will lead to a better understanding of the diversity and evolution of Wolbachia for its utility as a biocontrol agent.

Borneol promotes berberine-induced cardioprotection in a rat model of myocardial ischemia/reperfusion injury via inhibiting P-glycoprotein expression.

Berberine is reported to protect the heart against ischemia/reperfusion (I/R) injury, although efficacy is limited by low bioavailability. This study aims to determine whether borneol, a classic guiding drug, can enhance the cardioprotection induced by berberine and to clarify the underlying mechanisms involving P-glycoprotein (P-gp) in the heart. Adult male Sprague Dawley rats were gavaged with berberine (200 mg/kg) with or without borneol (100 mg/kg) for 7 consecutive days. A rat model of myocardial I/R injury was established by 30 min left coronary artery occlusion followed with 120 min reperfusion. The arrhythmia score, cardiac enzyme content, and myocardial infarct size were determined following reperfusion. Heart tissues were collected for Western blot and immunofluorescence analyses to measure the protein expression levels of Bcl-2, Bax, and P-gp. The results showed that administration of berberine protected the heart against I/R injury, as demonstrated by lower arrhythmia scores, serum cTnI contents, myocardial infarct size, and cardiomyocytes apoptosis. Moreover, borneol substantially enhanced the cardioprotective effects of berberine. Western blot and immunofluorescence analyses showed that both berberine and I/R injury did not alter P-gp expression in heart. In contrast, borneol combined with berberine significantly reduced P-gp levels by 43.4% (P = 0.0240). Interestingly, treatment with borneol alone decreased P-gp levels, but did not protect against myocardial I/R injury. These findings suggest that borneol, as an adjuvant drug, improved the cardioprotective effects of berberine by inhibiting P-gp expression in heart. Borneol combined with berberine administration provides a new strategy to protect the heart against I/R injury.

The mechanisms, hallmarks, and therapies for brain aging and age-related dementia.

Age-related cognitive decline and dementia are significant manifestations of brain aging. As the elderly population grows rapidly, the health and socio-economic impacts of cognitive dysfunction have become increasingly significant. Although clinical treatment of dementia has faced considerable challenges over the past few decades, with limited breakthroughs in slowing its progression, there has been substantial progress in understanding the molecular mechanisms and hallmarks of age-related dementia (ARD). This progress brings new hope for the intervention and treatment of this disease. In this review, we categorize the latest findings in ARD biomarkers into four stages based on disease progression: healthy brain, pre-clinical, mild cognitive impairment, and dementia. We then systematically summarize the most promising therapeutic approaches to prevent or slow ARD at four levels: genome and epigenome, organelle, cell, and organ and organism. We emphasize the importance of early prevention and detection, along with the implementation of combined treatments as multimodal intervention strategies, to address brain aging and ARD in the future.

Render help or stand by? The effect of group size on third-party punishment and its neural mechanisms.

Third-party punishment (TPP) is the punishment that an individual executes on a violator as a third party or observer to maintain social norms. Many studies have provided insights into the neural mechanisms of third-party punishment in group environments. Still, only some studies have focused on the neural mechanisms of third-party punishment in different group sizes. This study used EEG analysis to explore the effects of group size on third-party punishment and its neural activity characteristics from the context of gain and loss. The results show that the punishment rate and amount of the third party in the small group size and loss context were significantly higher than that in the large group size and gain context. EEG results showed that third-party punishment in small groups induced greater P2 than in large groups. In the loss context, the third-party punishment in the large group size induced more negative LNP and activated more theta band activation than in the small group. The results showed that the motivation of the third party to seek a positive reputation in the small size exceeds the balance of its economic interests and tends to punish the violator for maintaining fair norms. The loss context plays a promoting role in this process. However, in the large size, the third-party consideration of its interests was stronger than the willingness to maintain social norms. This study provided neuroscientific evidence for third-party punishment to maintain fair norms in a group environment and further explanations from neuroscience for understanding Indirect Reciprocity Theory.

Association between toxicity-index of diquat and in-hospital mortality in patients with acute diquat poisoning: a retrospective cohort study.

BackgroundThis study investigates the impact of diquat toxicity levels on in-hospital mortality rates among patients with acute diquat poisoning. It aims to clarify the relationship between diquat toxicity scores and the likelihood of death during hospitalization.MethodsA retrospective cohort study was conducted on 98 individuals with acute diquat poisoning. Data on post-ingestion time, initial diquat plasma concentration, and clinical outcomes were systematically collected for all participants. The toxicity-index of diquat was calculated based on post-ingestion time and initial diquat plasma concentration. Logistic regression analysis was utilized to assess the association between toxicity-index of diquat and in-hospital mortality rates, adjusting for potential confounding variables such as age, comorbidities, and treatment interventions.ResultsThe study found that the overall prevalence of in-hospital mortality was 34.7%, with 58.2% in males. The multivariable-adjusted regression coefficient for in-hospital mortality associated with the toxicity-index was 1.09, with a 95% confidence interval (CI) of 1.01-1.17. Subsequent exploratory subgroup analysis indicated that there were no significant interactions (all P values for interaction were >0.05).ConclusionsThe study found that higher diquat toxicity-index values correlate with increased in-hospital mortality in acute diquat poisoning cases, indicating that the toxicity-index could be a useful biomarker for assessing mortality risk.