Efficacy Analysis of Endoscopic-Assisted Traditional Surgery and Traditional Surgery for Sinonasal Malignant Melanoma.

Object: To analyze the effect of traditional surgery and endoscope-assisted traditional surgery on patients with sinonasal malignant melanoma (SMM), and to explore the effective treatment of SMM. Methods: The clinicopathological data and surgical methods of 47 patients with SMM, diagnosed in the Department of Otorhinolaryngology-Head and Neck Surgery at the Third People's Hospital of Yunnan Province from October 2000 to June 2020, were retrospectively analyzed. Among them, 26 cases were treated with traditional surgery, and 21 cases were treated with endoscope-assisted traditional surgery. The 3 and 5 year local recurrence and survival rates were monitored and compared. Results: The 3 year local recurrence rate was compared between the 2 groups: χ2 = 5.4558, P = .020 (P < .05), the endoscope-assisted traditional surgery group had a lower 3 year local recurrence rate. The 3 year survival rate was compared between the 2 groups: χ2 = 1.0231, P = .312 (P > .05), the difference in 3 year survival was not significant between the 2 groups. The 5 year local recurrence rate was compared between the 2 groups: χ2 = 4.4052, P = .036 (P < .05), the endoscope-assisted traditional surgery group had a lower 5 year local recurrence rate. The 5 year survival rate was compared between the 2 groups: χ2 = 4.3085, P = .038 (P < .05), the endoscope-assisted traditional surgery group had a higher 5 year survival rate. Therefore, there were significant differences in the local recurrence rates at 3 and 5 years, as well as the 5 year survival rate, between endoscope-assisted traditional surgery and traditional surgery in the treatment of SMM. Conclusion: Endoscope-assisted traditional surgery can remove local lesions of SMM more completely, reduce the local recurrence rate, and improve the 5 year survival rate of patients.

Novel Metal-Free Nanozyme for Targeted Imaging and Inhibition of Atherosclerosis via Macrophage Autophagy Activation to Prevent Vulnerable Plaque Formation and Rupture.

Atherosclerosis is a primary cause of cardiovascular and cerebrovascular diseases, with the unpredictable rupture of vulnerable atherosclerotic plaques enriched with lipid-laden macrophages being able to lead to heart attacks and strokes. Activating macrophage autophagy presents itself as a promising strategy for preventing vulnerable plaque formation and reducing the risk of rupture. In this study, we have developed a novel metal-free nanozyme (HCN@DS) that integrates the functions of multimodal imaging-guided therapy for atherosclerosis. HCN@DS has demonstrated high macrophage-targeting abilities due to its affinity toward scavenger receptor A (SR-A), along with excellent photoacoustic and photothermal imaging capabilities for guiding the precise treatment. It combines mild photothermal effects with moderate reactive oxygen species (ROS) generation to treat atherosclerosis. This controlled approach activates autophagy in atherosclerotic macrophages, inhibiting foam cell formation by reducing the uptake of oxidized low-density lipoproteins (oxLDL) and promoting efferocytosis and cholesterol efflux in macrophages. Additionally, it prevents plaque rupture by inhibiting apoptosis and inflammation within the plaque. Therefore, this metal-free nanozyme holds great potential for reducing the risk of atherosclerosis due to its high biosafety, excellent targeting ability, dual-modality imaging capability, and appropriate modulation of autophagy.

An intervention study of poly-victimization among rural left-behind children based on the theoretical framework of planned behavior.

BACKGROUND: Poly-victimization (PV) not only threatens physical and mental health but also causes a range of social problems. Left-behind children in rural areas are more likely to experience PV problems. However, there have been fewer studies on PV among rural children, and even fewer intervention studies. OBJECTIVE: The difference-in-differences method was employed to analyze the impact of intervention measures, based on the theory of planned behavior, on PV among left-behind children in rural areas. METHODS: The study subjects were left-behind children from six middle schools in two cities in southern China, who completed the baseline survey from 2020 to 2021. They were divided into a control group and an intervention group, each consisting of 228 cases, based on their schools. Before and after the intervention, the Self-made victimization-related knowledge, attitude, and practice questionnaire, Poly-victimization scale, and Middle school students' coping style scale were used to evaluate the victimization-related KAP(knowledge, attitude, and practice), victimization occurrence, and coping styles of left-behind children, respectively. Stata 15.0 was used to establish a difference-in-differences regression model to analyze the impact of the intervention measures on poly-victimization and coping styles. RESULTS: Mixed Anova revealed that after the intervention, the KAP scores of the intervention group were significantly higher than those of the control group (p < 0.05). After the intervention, the incidence of child victimization in the intervention group dropped to 9.60% (n = 22), lower than in the baseline survey, with a statistically significant difference (p < 0.01). The incidence of PV among children in the intervention group was lower than that in the control group, with the difference being statistically significant (p < 0.01). The net reduction in the incidence of PV among children was 21.20%. After the intervention, the protection rate for preventing PV among children was 73.33%, and the effect index was 3.75. The intervention improved children's coping styles, problem-solving, and help-seeking, while reducing negative coping styles such as avoidance and venting, with the differences being statistically significant (p < 0.05). CONCLUSION: Intervention measures based on the theory of planned behavior reduce the occurrence of PV among left-behind children, and the intervention effects on different types of victimization are also different.

Exploring the variations in molecular characteristics of dissolved organic matter driven by aquaculture types.

In recent decades, global aquaculture has expanded rapidly, raising concerns about coastal environmental degradation due to unregulated or poorly regulated discharge of aquaculture tailwater. Despite the crucial role of dissolved organic matter (DOM) in biogeochemical processes and aquatic biodiversity, the influence of aquaculture type on the molecular characteristics of DOM remains largely unexplored. Herein, this study investigated the variations in chemical and spectroscopic properties as well as molecular characteristics and composition of DOM across different aquaculture types including crustacean, fish and shellfish. Our findings revealed notable differences in DOM quantities among different aquaculture types, with crustacean and fish aquaculture water containing higher DOM amount compared to shellfish aquaculture water. This disparity can be attributed to the more frequent formulated feeds of crustacean and fish in contrast to shellfish aquaculture. Furthermore, distinct differences were also observed in the characteristics and composition of DOM among the different aquaculture waters. Specifically, DOM in shellfish aquaculture water exhibited a higher abundance of unsaturated and reduced molecules as well as increased aromaticity compared to the other two aquaculture waters. Conversely, DOM from fish aquaculture water showed a greater contribution from terrestrial origin characterized by elevated levels of plant-based components such as lignin-like and tannin-like compounds. Interestingly, DOM from shellfish aquaculture water contained lower levels of microbial-derived components such as lipid-like and protein-like compounds, likely due to reduced microorganism populations resulting from lower nutrients availability and higher salinity. Overall, these significant variations in characteristics and composition of DOM underscore the potential impacts of aquaculture type on the DOM biogeochemical cycle and the environmental quality in aquatic ecosystems.

RBNE-CMI: An Efficient Method for Predicting circRNA-miRNA Interactions via Multiattribute Incomplete Heterogeneous Network Embedding.

Circular RNA (circRNA)-microRNA (miRNA) interaction (CMI) plays crucial roles in cellular regulation, offering promising perspectives for disease diagnosis and therapy. Therefore, it is necessary to employ computational methods for the rapid and cost-effective prediction of potential circRNA-miRNA interactions. However, the existing methods are limited by incomplete data; therefore, it is difficult to model molecules with different attributes on a large scale, which greatly hinders the efficiency and performance of prediction. In this study, we propose an effective method for predicting circRNA-miRNA interactions, called RBNE-CMI, and introduce a framework that can embed incomplete multiattribute CMI heterogeneous networks. By combining the proposed method, we integrate different data sets in the CMI prediction field into one incomplete network for modeling, achieving superior performance in 5-fold cross-validation. Moreover, in the prediction task based on complete data, the proposed method still achieves better performance than the known model. In addition, in the case study, we successfully predicted 18 of the 20 potential cancer biomarkers. The data and source code can be found at https://github.com/1axin/RBNE-CMI.

Targeting cuproptosis for cancer therapy: mechanistic insights and clinical perspectives.

Cuproptosis is a newly identified form of cell death induced by excessive copper (Cu) accumulation within cells. Mechanistically, cuproptosis results from Cu-induced aggregation of dihydrolipoamide S-acetyltransferase, correlated with the mitochondrial tricarboxylic acid cycle and the loss of iron-sulfur cluster proteins, ultimately resulting in proteotoxic stress and triggering cell death. Recently, cuproptosis has garnered significant interest in tumor research due to its potential as a crucial therapeutic strategy against cancer. In this review, we summarized the cellular and molecular mechanisms of cuproptosis and its relationship with other types of cell death. Additionally, we reviewed the current drugs or strategies available to induce cuproptosis in tumor cells, including Cu ionophores, small compounds, and nanomedicine. Furthermore, we targeted cell metabolism and specific regulatory genes in cancer therapy to enhance tumor sensitivity to cuproptosis. Finally, we discussed the feasibility of targeting cuproptosis to overcome tumor chemotherapy and immunotherapy resistance and suggested future research directions. This study suggested that targeting cuproptosis could open new avenues for developing tumor therapy.

Haptoglobin phenotype and levels in type 2 diabetes and effects of fenofibrate.

AIMS/HYPOTHESIS: In diabetes haptoglobin (Hp) 2 vs Hp 1 allelic product is associated with cardiac and renal complications. Few studies report both Hp phenotype and Hp levels. In a Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial substudy we evaluated the Hp phenotype, Hp levels, and fenofibrate effects. MATERIALS AND METHODS: In 480 adults with type 2 diabetes (T2D) the Hp phenotype was assessed and the Hp level quantified (both using ELISAs assays) in plasma from baseline, after 6 weeks of fenofibrate, and (in n = 200) at 2 years post-randomization to fenofibrate or placebo. RESULTS: The Hp phenotypes 1-1, 2-1, and 2-2 frequencies were 15%, 49%, and 36%, respectively. Baseline Hp levels differed by phenotype (P < 0.0001) and decreased (median 21%) after 6 weeks fenofibrate in all phenotypes (adjusted mean (95% CI): -0.27 (-0.32, -0.23) mg/mL in Hp 1-1, -0.29 (-0.31, -0.27) mg/mL in Hp 2-1 and -0.05 (-0.07, -0.02) mg/mL in Hp 2-2 (P = 0.005 and P = 0.055 vs Hp 1-1 and Hp 2-1, respectively)). At 2 years post-randomization the Hp levels in the placebo group had returned to baseline, whilst the fenofibrate-group levels remained similar to the 6 week levels. CONCLUSIONS: In type 2 diabetes, Hp levels differ by Hp phenotype and are decreased by fenofibrate in all phenotypes, but the effect is diminished in Hp 2-2.

Trends in transport injuries burden and risk factors among children under 14 years old in China: 1990-2019.

BACKGROUND: Transport injuries (TI) remains one of leading causes of death in children in China. This study aimed to analyze the temporal trend of disease burden and associated risk factors of TI among children aged 0-14 years in China, utilizing data from 1990 to 2019. METHODS: We retrieved data of disease burden and risk factors of TI among children aged 0-14 year in China from 1990 to 2019 from the Global Burden of Disease (GBD) dataset. We estimated incidence rate, death rate, and disability adjusted life years (DALYs) rate with a 95% uncertainty interval (95% UI), stratified by age, sex, and all type-road users. Trends in disease burden with annual percentage changes (APC) and average annual percent change (AAPC) were performed by Joinpoint regression model. RESULTS: The incidence rate (AAPC = 1.18%, P < 0.001) of TI among children aged 0-14 years showed an increasing trend, whereas mortality rate (AAPC = -3.87%, P < 0.001) and DALYs rate (AAPC = -3.83%, P < 0.001) decreased annually. Notably, boys experienced a higher increase in incidence (1.30%) compared to girls (1.06%), but a faster decrease in mortality and DALYs rate (-3.90% vs. -3.82%, -3.88% vs. -3.79%, respectively) (Pall < 0.001). Declines in death rates and DALYs rates were observed across all age groups (Pall < 0.001), while remained the highest among children aged 0-4 in 2019. Among different road-type users, cyclist road injuries were identified as the primary cause of TI (182.3 cases per 100,000) while pedestrians were the group with the highest mortality (2.9 cases per 100,000) and DALYs rate (243 cases per 100,000) in 2019. Besides, alcohol use was a significant risk factors for TI, while low temperature appeared to be a protective factor. CONCLUSION: Future efforts must prioritize raising awareness among children and their guardians to mitigate the disease burden of TI in children. It's critical to enhance preventive interventions for boys, children aged 0-4 and vulnerable road users such as pedestrians and cyclists in future.

Neoadjuvant cabozantinib restores CD8+ T cells in patients with locally advanced non-metastatic clear cell renal cell carcinoma: a phase 2 trial.

Cabozantinib is an oral multikinase inhibitor approved for treatment in metastatic renal cell carcinoma (RCC). We hypothesized that neoadjuvant cabozantinib could downstage localized tumors, facilitating partial nephrectomy, and facilitating surgery in patients with locally advanced tumors that would require significant adjacent organ resection. We, therefore, conducted a phase 2, single-arm trial of cabozantinib treatment for 12 weeks in 17 patients with locally advanced biopsy-proven non-metastatic clear cell RCC before surgical resection. Six patients (35%) experienced a partial response, and 11 patients (65%) had stable disease. We identified that plasma cell-free DNA (cfDNA), VEGF, c-MET, Gas6, and AXL were significantly increased while VEGFR2 decreased during cabozantinib treatments. There was a trend towards CD8+ T cells becoming activated in the blood, expressing the proliferation marker Ki67 and activation markers HLA-DR and CD38. Cabozantinib treatment depleted myeloid populations acutely. Importantly, immune niches made up of the stem-like CD8+ T cells and antigen presenting cells were increased in every patient. These data suggest that cabozantinib treatment was clinically active and safe in the neoadjuvant setting in patients with locally advanced non-metastatic clear cell RCC and activated the anti-tumor CD8+ T cell response. The trial is registered at ClinicalTrials.gov under registration no. NCT04022343.

Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor- and Cygb-associated signaling pathways.

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease. Consequently, enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression. Nonetheless, non-pharmacological interventions aimed at inducing adult neurogenesis are currently limited. Although individual non-pharmacological interventions, such as aerobic exercise, acousto-optic stimulation, and olfactory stimulation, have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease, the therapeutic effect of a strategy that combines these interventions has not been fully explored. In this study, we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months. Amyloid deposition became evident at 4 months, while neurogenesis declined by 6 months, further deteriorating as the disease progressed. However, following a 4-week multifactor stimulation protocol, which encompassed treadmill running (46 min/d, 10 m/min, 6 days per week), 40 Hz acousto-optic stimulation (1 hour/day, 6 days/week), and olfactory stimulation (1 hour/day, 6 days/week), we found a significant increase in the number of newborn cells (5'-bromo-2'-deoxyuridine-positive cells), immature neurons (doublecortin-positive cells), newborn immature neurons (5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells), and newborn astrocytes (5'-bromo-2'-deoxyuridine-positive/ glial fibrillary acidic protein-positive cells). Additionally, the amyloid-beta load in the hippocampus decreased. These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice. Furthermore, cognitive abilities were improved, and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation, as evidenced by Morris water maze, novel object recognition, forced swimming test, and tail suspension test results. Notably, the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2 weeks after treatment cessation. At the molecular level, multifactor stimulation upregulated the expression of neuron-related proteins (NeuN, doublecortin, postsynaptic density protein-95, and synaptophysin), anti-apoptosis-related proteins (Bcl-2 and PARP), and an autophagy-associated protein (LC3B), while decreasing the expression of apoptosis-related proteins (BAX and caspase-9), in the hippocampus of amyloid precursor protein/presenilin 1 mice. These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways. Furthermore, serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis, oxidative damage, and cognition. Collectively, these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.

Interfacial electronic modulation of NiCo decorated nano-flowered MoS2 on carbonized wood as a remarkable bifunctional electrocatalyst for boosting overall water splitting.

The development of a cost-effective and efficient bifunctional electrode for overall water splitting holds significant importance in accelerating the sustainable advancement of hydrogen energy. The present study involved a bifunctional catalytic electrode was prepared by loading NiCo-modified 1T/2H MoS2 onto carbonized wood (NiCo-MoS2-CW) using the hydrothermal and electrodeposition techniques. The XPS analysis revealed that NiCo-modified MoS2 exhibited a weak electron characteristic, which facilitated the ionization of H2O and significantly enhanced the Volmer step. The XPS analysis unveiled that NiCo-modified MoS2 displayed a weak electron characteristic, thereby promoting the ionization of H2O and substantially augmenting the Volmer step. The electrocatalytic performance of the NiCo-MoS2-CW in 1.0 M KOH is remarkably impressive, exhibiting minimal overpotentials of only 64 mV (10 mA cm-2) and 216 mV (50 mA cm-2) for the hydrogen evolution reaction and oxygen evolution reaction, respectively. The NiCo-MoS2-CW || NiCo-MoS2-CW electrolytic cell can achieve a cell voltage of only 1.69 V to achieve a current density of 50 mA cm-2. Overall, this study proposes a potential approach to improve the catalytic efficiency of overall water splitting by modulating the interfacial electronic properties of MoS2.

Problem-solving ability and future time perspective among the Chinese nursing interns: The mediating role of future work self.

BACKGROUND: The significance of problem-solving ability has been confirmed in numerous studies worldwide, highlighting its role in enhancing the skills of nursing interns and reducing psychological pressure. However, existing research indicates that the problem-solving ability of nursing interns urgently needs to be further improved. Limited research has been conducted on the problem-solving ability of nursing interns, and the correlations among problem-solving ability, future time perspective, and future work self of Chinese nursing interns are unclear. OBJECTIVES: To investigate problem-solving ability, future time perspective, and future work self among the Chinese nursing interns, and to examine the relationships among these variables. Additionally, the study aims to explore the mediating role of future work self between problem-solving ability and future time perspective. METHODS: A cross-sectional and correlational design was employed, adhering to the quality reporting conformed to the STROBE Checklist. From May 8, 2023, to February 15, 2024, 1,251 nursing interns were recruited from 15 tertiary grade-A hospitals across six cities in China. The Demographic Characteristics Questionnaire, Social Problem-Solving Inventory, Future Time Perspective Inventory, and Future Work Self Scale were used. The data was analyzed using descriptive statistics, univariate, correlation, and process plug-in mediation effect analyses. RESULTS: The total scores for problem-solving ability, future time perspective, and future work self were 64.39 ± 18.55, 45.08 ± 11.37, and 16.92 ± 5.28, respectively. Problem-solving ability was positively correlated with future time perspective (r = 0.638, p < 0.001) and future work self (r = 0.625, p < 0.001). Additionally, future work self partially mediated mediating role between problem-solving ability and future time perspective, accounting for 39.7% of the total effect. CONCLUSION: The problem-solving ability, future time perspective, and future work self among the Chinese nursing interns were relatively moderate, indicating a need for improvement. It is suggested that nursing managers and educators should actively implement career management and planning programs. By enhancing the future time perspective and future work self of nursing interns, their problem-solving ability can be improved. This, in turn, will facilitate their adaptation to clinical work, enhance the quality of nursing care, and promote the development of their nursing profession.

Comparing oxygen therapies for hypoxemia prevention during gastrointestinal endoscopy under procedural sedation: A systematic review and network meta-analysis.

STUDY OBJECTIVE: Hypoxemia is the most frequent adverse event observed during gastrointestinal endoscopy under procedural sedation. An optimum oxygen therapy has still not been conclusively determined. DESIGN: A systematic review and network meta-analysis of randomized clinical trials. SETTING: Digestive Endoscopy Center. PATIENTS: Adults (≥18 years old and of both sexes) during gastrointestinal endoscopy under procedural sedation. INTERVENTIONS: Pubmed, MEDLINE, Web of Science, Embase, and Clinicaltrials.gov. were searched until June 30, 2023. Randomized clinical trials (RCTs) comparing any oxygen therapy with another oxygen therapy or with placebo (nasal cannula, NC) were included. MEASUREMENT: The primary outcome was the incidence of hypoxemia, defined as the pulse oxygen saturation (SpO2). Random-effects network meta-analyses were performed. Data are reported as odds ratios (OR), prediction intervals (PrI) and 95% CI. Bias risk was evaluated following the guidelines outlined by the Cochrane Collaboration. The quality of evidence was evaluated through the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. MAIN RESULTS: We included 27 RCTs with a total of 7552 patients. Compared to the use of NC, non-invasive positive pressure ventilation (NIPPV) demonstrated superior efficacy in mitigating hypoxemia (NIPPV vs. NC, OR = 0.16, 95% CI: 0.08-0.31, 95% PrI: 0.06-0.41), followed by Wei nasal jet tube (WNJT) (WNJT vs. NC, OR = 0.17, 95% CI: 0.10-0.30, 95% PrI: 0.07-0.42). The efficacy for preventing hypoxemia was ranked as follows: NIPPV > WNJT > oropharynx/nasopharyngeal catheter > high-flow nasal oxygenation > nasal mask > NC. CONCLUSIONS: During gastrointestinal endoscopy under procedural sedation, all other advanced oxygen therapies were found to be more efficacious than nasal cannula. NIPPV and WNJT appear to be the most efficacious oxygen therapy for preventing hypoxemia. Additionally, clinicians should make a choice regarding the most suitable oxygen therapy based on the risk population, type of endoscopy and adverse events.

Improving the identification of pollution source areas with catchment-resolution sensitivity analysis.

The significant impacts of total nitrogen (TN) and total phosphorus (TP) on riverine ecosystems underscores the critical need to identify the primary nutrient source areas in watersheds. This study aims to unravel the influences of terrain and land use types on mean monthly TN (TNM) and mean monthly TP (TPM) export across varying catchment resolutions in the Qiantang River Watershed of China. The findings of this study illuminated the critical role of topography in understanding nutrient dynamics, wielding a profound influence over water flow patterns and nutrient dispersion. Both land slope and Stream Power Index (SPI) displayed substantial negative correlations (r < -0.6) with TNM and TPM concentrations, whereas the Topographic Wetness Index (TWI) showed positive correlations with the nutrient indexes. In addition to terrain characteristics, impervious land surfaces had a positive correlation with nutrient concentrations, while grassland and forest areas exhibited negative correlations. Results further underscored the substantial influence of catchment resolution on correlations between watershed properties and riverine nutrient concentrations. It was imperative to choose an effective catchment resolution in watershed delineation - not too coarse, nor too fine - to accurately capture the topographic and land use impacts on nutrient dynamics. With the most appropriate catchment size (Catchment 700 km2), the critical pollution source areas for TN and TP pollution were identified, and thus could be used to guide future pollution reduction efforts. The study not only highlights the importance of identifying an appropriate catchment size for water pollution, but also emphasizes the necessity of effectively extracting critical pollution source areas to mitigate water nutrient pollution and increase the ecological integrity of the Qiantang River Watershed.

The scheduling of adolescence with Netrin-1 and UNC5C.

Dopamine axons are the only axons known to grow during adolescence. Here, using rodent models, we examined how two proteins, Netrin-1 and its receptor, UNC5C, guide dopamine axons toward the prefrontal cortex and shape behaviour. We demonstrate in mice (Mus musculus) that dopamine axons reach the cortex through a transient gradient of Netrin-1-expressing cells - disrupting this gradient reroutes axons away from their target. Using a seasonal model (Siberian hamsters; Phodopus sungorus) we find that mesocortical dopamine development can be regulated by a natural environmental cue (daylength) in a sexually dimorphic manner - delayed in males, but advanced in females. The timings of dopamine axon growth and UNC5C expression are always phase-locked. Adolescence is an ill-defined, transitional period; we pinpoint neurodevelopmental markers underlying this period.

Isobavachalcone Exhibits Potent Antifungal Efficacy by Inhibiting Enolase Activity and Glycolysis in Candida albicans.

Invasive fungal diseases (IFDs) are becoming increasingly acknowledged as a significant concern linked to heightened rates of morbidity and mortality. Regrettably, the available antifungal therapies for managing IFDs are constrained. Emerging evidence indicates that enolase holds promise as a potential target protein for combating IFDs; however, there is currently a deficiency in antifungal medications specifically targeting enolase. This study establishes that isobavachalcone (IBC) exhibits noteworthy antifungal efficacy both in vitro and in vivo. Moreover, our study has demonstrated that IBC effectively targets Eno1 in Candida albicans (CaEno1), resulting in the suppression of the glycolytic pathway. Additionally, our research has indicated that IBC exhibits a higher affinity for CaEno1 compared to human Eno1 (hEno1), with the presence of isoprenoid in the side chain of IBC playing a crucial role in its ability to inhibit enolase activity. These findings contribute to the comprehension of antifungal approaches that target Eno1, identifying IBC as a potential inhibitor of Eno1 in human pathogenic fungi.

HNRNP I promotes IRAK1 degradation to reduce podocyte apoptosis and inflammatory response alleviating renal injury in diabetic nephropathy.

Podocytes maintain renal filtration integrity when the glomerular filtration barrier (GFB) is integrated. Impairment or attrition of podocytes, leading to compromised GFB permeability, constitutes the primary etiology of proteinuria and is a hallmark pathological feature of diabetic nephropathy (DN). This study centers on Heterogeneous Nuclear Ribonucleoprotein I (HNRNP I), an RNA-binding protein, delineating its role in facilitating DN-induced renal damage by modulating podocyte health. Comparative analyses in renal biopsy specimens from DN patients and high-glucose-challenged podocyte models in vitro revealed a marked downregulation of HNRNP I expression relative to normal renal tissues and podocytes. In vitro assays demonstrated that high-glucose conditions precipitated a significant reduction in podocyte viability and an escalation in markers indicative of apoptosis. Conversely, HNRNP I overexpression was found to restore podocyte viability and attenuate apoptotic indices. IRAK1, a gene encoding a protein integral to inflammatory signaling, was shown to interact with HNRNP I, which promotes IRAK1 degradation. This interaction culminates in suppressing the PI3K/AKT/mTOR signaling pathway, thereby diminishing podocyte apoptosis and mitigating renal damage in DN. This investigation unveils the mechanistic role of HNRNP I in DN for the first time, potentially informing novel therapeutic strategies for DN renal impairment.

Observation of therapeutic effect of lamp irradiation combined with purple gromwell oil gauze on alleviating intestinal colic in patients.

BACKGROUND: Intestinal colic is a common complication in patients who have undergone radical surgery for colorectal cancer. Traditional Chinese medicine has advantages, including safety and stability, for the treatment of intestinal colic. Lamp irradiation for abdominal ironing has been applied in the treatment of many gastrointestinal diseases. Purple gromwell oil has the effects of clearing heat, cooling blood, reducing swelling, and relieving pain. AIM: To investigate the impact of lamp irradiation combined with purple gromwell oil gauze on ameliorating intestinal colic in patients after radical surgery for colorectal cancer. METHODS: A total of 120 patients who experienced postoperative intestinal colic complications after radical surgery for colorectal cancer and who were admitted to Foshan Traditional Chinese Medicine Hospital between June 2019 and March 2023 were enrolled as study subjects. The patients were divided into a control group (60 patients) and an observation group (60 patients) based on treatment method. The control group was treated with lamp irradiation, while the observation group was treated with lamp irradiation and external application of purple gromwell oil gauze. The clinical efficacy, Numeric Rating Scale (NRS) score, duration of symptoms, and rate of adverse reaction occurrence were further compared between the two groups. RESULTS: The general effective rate in the observation group was 95.00%, which was significantly higher than that in the control group (86.67%, P < 0.05). Before treatment, there was no significant difference in the duration of symptoms between the groups (P > 0.05). After 1, 2, 3, and 4 d of treatment, the duration of symptoms in both groups were decreased, and the duration in the observation group was significantly lower than that in the control group (96.54 ± 9.57 vs 110.45 ± 11.23, 87.26 ± 12.07 vs 104.44 ± 11.68, 80.45 ± 16.21 vs 99.44 ± 14.95, 73.18 ± 15.58 vs 92.17 ± 14.20; P < 0.05). After 1, 3, 5, and 7 d of treatment, the NRS scores in both groups were decreased, and the NRS scores in the observation group were significantly lower than those in the control group (3.56 ± 0.41 vs 4.04 ± 0.58, 3.07 ± 0.67 vs 3.74 ± 1.02, 2.52 ± 0.76 vs 3.43 ± 0.85, 2.03 ± 0.58 vs 3.03 ± 0.82; P < 0.05). There was no significant difference in the rate of adverse reaction occurrence between the groups (P > 0.05). CONCLUSION: The use of lamp irradiation combined with purple gromwell oil gauze in patients with intestinal colic after radical surgery for colorectal cancer can reduce symptom duration, alleviate intestinal colic, and improve treatment efficacy, and this approach is safe. It is worth promoting the use of this treatment in clinical practice.