Strigolactones alleviate AlCl3 stress by vacuolar compartmentalization and cell wall blocking in apple.

Poor management and excess fertilization of apple (Malus domestica Borkh.) orchards are causing increasingly serious soil acidification, resulting in Al toxicity and direct poisoning of roots. Strigolactones (SLs) are reported to be involved in plant responses to abiotic stress, but their role and mechanism under AlCl3 stress remain unknown. Here, we found that applying 1 µm GR24 (an SL analoge) significantly alleviated AlCl3 stress of M26 apple rootstock, mainly by blocking the movement of Al through cell wall and by vacuolar compartmentalization of Al. RNA-seq analysis identified the core transcription factor gene MdWRKY53, and overexpressing MdWRKY53 enhanced AlCl3 tolerance in transgenic apple plants through the same mechanism as GR24. Subsequently, we identified MdPMEI45 (encoding pectin methylesterase inhibitor) and MdALS3 (encoding an Al transporter) as downstream target genes of MdWRKY53 using chromatin immunoprecipitation followed by sequencing (ChIP-seq). GR24 enhanced the interaction between MdWRKY53 and the transcription factor MdTCP15, further increasing the binding of MdWRKY53 to the MdPMEI45 promoter and inducing MdPMEI45 expression to prevent Al from crossing cell wall. MdWRKY53 also bound to the promoter of MdALS3 and enhanced its transcription to compartmentalize Al in vacuoles under AlCl3 stress. We therefore identified two modules involved in alleviating AlCl3 stress in woody plant apple: the SL-WRKY+TCP-PMEI module required for excluding external Al by blocking the entry of Al3+ into cells and the SL-WRKY-ALS module allowing internal detoxification of Al through vacuolar compartmentalization. These findings lay a foundation for the practical application of SLs in agriculture.

Time-dependent systolic blood pressure within 72 h after endovascular treatment in large vessel occlusion stroke.

BACKGROUND: The association of systolic blood pressure (SBP) and ischemic stroke outcome has recently been proved to be varied at different time points within 72 h after acute ischemic stroke onset; however, the specific status of how SBP affects prognosis at different time points within 72 h after endovascular treatment (EVT) among patients with large vessel occlusion (LVO) remains unclear. METHODS: Consecutive LVO patients treated with EVT were enrolled in our study. BP data were collected at eight time points (1, 2, 4, 8, 16, 24, 48, and 72 h post-EVT). Outcome measure of interest was functional dependence, which was defined as mRS >2 at 90 days. RESULTS: A total of 406 LVO patients treated with EVT from 2016 to 2022 were included. At 16 h after EVT, the relationship between SBP and functional dependence showed a nonlinear association. At other time points after EVT, SBP had linear relationships with functional dependence. Furthermore, higher SBP, as either a linear or quadratic term, had an adverse effect on functional outcome. In addition, three SBP trajectories were observed, and the high-to-low group was independently associated with functional dependence. CONCLUSION: Taken together, higher SBP within the first 72 h after EVT has a time-dependent association with adverse clinical outcomes. Optimal blood pressure management during the first 72 h after EVT may be important to improve clinical outcome.

Core microbiota for nutrient digestion remained and ammonia utilization increased after continuous batch culture of rumen microbiota in vitro.

Introduction: This study aimed to investigate the digestive function, urea utilization ability, and bacterial composition changes in rumen microbiota under high urea (5% urea in diet) over 23 days of continuous batch culture in vitro. Methods: The gas production, dry matter digestibility, and bacterial counts were determined for the continuously batch-cultured rumen fluid (CRF). The changes in fermentation parameters, NH3-N utilization efficiency, and microbial taxa were analyzed in CRF and were compared with that of fresh rumen fluid (RF), frozen rumen fluid (FRF, frozen rumen fluid at -80°C for 1 month), and the mixed rumen fluid (MRF, 3/4 RF mixed with 1/4 CRF) with in vitro rumen fermentation. Results: The results showed that the dry matter digestibility remained stable while both the microbial counts and diversity significantly decreased over the 23 days of continuous batch culture. However, the NH3-N utilization efficiency of the CRF group was significantly higher than that of RF, FRF, and MRF groups (p < 0.05), while five core genera including Succinivibrio, Prevotella, Streptococcus, F082, and Megasphaera were retained after 23 days of continuous batch culture. The NH3-N utilization efficiency was effectively improved after continuous batch culture in vitro, and Streptococcus, Succinivibrio, Clostridium_sensu_stricto_1, p.251.o5, Oxalobacter, Bacteroidales_UCG.001, and p.1088.a5_gut_group were identified to explain 75.72% of the variation in NH3-N utilization efficiency with the RandomForest model. Conclusion: Thus, core bacterial composition and function retained under high urea (5% urea in diet) over 23 days of continuous batch culture in vitro, and bacterial biomarkers for ammonia utilization were illustrated in this study. These findings might provide potential applications in improving the efficiency and safety of non-protein nitrogen utilization in ruminants.

Short-term exposure to extreme temperature and outpatient visits for respiratory diseases among children in the northern city of China: a time-series study.

BACKGROUND: Although studies have indicated that extreme temperature is strongly associated with respiratory diseases, there is a dearth of studies focused on children, especially in China. We aimed to explore the association between extreme temperature and children's outpatient visits for respiratory diseases and seasonal modification effects in Harbin, China. METHODS: A distributed lag nonlinear model (DLNM) was used to explore the effect of extreme temperature on daily outpatient visits for respiratory diseases among children, as well as lag effects and seasonal modification effects. RESULTS: Extremely low temperatures were defined as the 1st percentile and 2.5th percentile of temperature. Extremely high temperatures were defined as the 97.5th percentile and 99th percentile of temperature. At extremely high temperatures, both 26 °C (97.5th) and 27 °C (99th) showed adverse effects at lag 0-6 days, with relative risks (RRs) of 1.34 [95% confidence interval (CI): 1.21-1.48] and 1.38 (95% CI: 1.24-1.53), respectively. However, at extremely low temperatures, both - 26 °C (1st) and - 23 °C (2.5th) showed protective effects on children's outpatient visits for respiratory diseases at lag 0-10 days, with RRs of 0.86 (95% CI: 0.76-0.97) and 0.85 (95% CI: 0.75-0.95), respectively. We also found seasonal modification effects, with the association being stronger in the warm season than in the cold season at extremely high temperatures. CONCLUSIONS: Our study indicated that extremely hot temperatures increase the risk of children's outpatient visits for respiratory diseases. Efforts to reduce the exposure of children to extremely high temperatures could potentially alleviate the burden of pediatric respiratory diseases, especially during the warm season.

Endovascular thrombectomy for acute ischemic stroke in elderly patients with large ischemic cores.

BACKGROUND: Understanding the benefits and risks of endovascular therapy (EVT) is crucial for elderly patients with large ischemic cores, as the combination of advanced age and extensive brain infarction may negatively impact clinical outcomes. METHODS: The study retrospectively analyzed clinical outcomes for elderly stroke patients (age ≥ 70) with large ischemic cores (Alberta Stroke Program Early CT Score [ASPECTS] < 6 or ischemic cores ≥ 70 ml) in the anterior circulation using data from our prospective database between June 2018 and January 2022. The effectiveness and risks of EVT in those patients were investigated, with the primary outcome being fair outcome (modified Rankin Scale, mRS ≤ 3). RESULTS: Among 182 elderly patients with large ischemic core volume (120 in the EVT group and 62 in the non-EVT group), 20.9% (38/182, 22.5% in the EVT group vs. 17.7% in the non-EVT group) achieved a fair outcome. Meanwhile, 49.5% (90/182, 45.8% in the EVT group vs. 56.5% in the non-EVT group) of them died at 3 months. The benefits of EVT numerically exceeded non-EVT treatment for those aged ≤ ~ 85 years or with a mismatch volume ≥ ~ 50 ml. However, after adjustment, EVT was associated with an increased risk of symptomatic intracranial hemorrhage (aOR 4.24, 95%CI 1.262-14.247). CONCLUSIONS: This study highlights the clinical challenges faced by elderly patients with large infarctions, resulting in poor outcomes at 3 months. EVT may still provide some benefits in this population, but it also carries an increased risk of intracranial hemorrhage.

Combining CD4 count, CD8 count and CD4/CD8 ratio to predict risk of mortality among HIV-positive adults after therapy: a group-based multi-trajectory analysis.

Introduction: Previous studies have indicated different immunological recovery trajectories based on CD4 count or CD4/CD8 ratio. However, these immune indicators are interconnected, and relying solely on one indicator may lead to inaccurate estimates. Therefore, it is essential to develop a comprehensive trajectory model that integrates CD4 count, CD8 count and CD4/CD8 ratio. Methods: We utilized a group-based multi-trajectory model to characterize the latent cluster of recovery based on measurements of CD4 count, CD8 count and CD4/CD8 ratio over a period of up to 96 months following ART initiation. Subsequently, we investigated the characteristics associated with trajectory groups, especially sex and age. Cox model and Kaplan-Meier survival curve were employed to assess differences in all-cause, AIDS-related and non-AIDS related mortality between trajectory groups. Results: A total of 14,718 eligible individuals were followed for a median of 55 months. Longitudinal model identified four subgroups: group 1 (32.5%, low CD4 and CD4/CD8 inversion), group 2 (25.9%, high CD8 and CD4/CD8 inversion), group 3 (27.2%, slow recovery of CD4 and CD4/CD8 inversion) and group 4 (14.4%, rapid increase of CD4 and normal CD4/CD8). Immune recovery was slower in male than in female, and in elders than in youngers. Compared to group 2, group 1 (adjusted hazard ratio [aHR]=3.28; 95% CI 2.33-4.60) and group 3 (aHR=1.56; 95% CI 1.09-2.24) had increased risk of all-cause mortality after adjusting for other factors. Besides, group 1 (aHR=2.17) and group 3 (aHR=1.58) had higher risk of non-AIDS related mortality, and group 1 (aHR=5.92) had significantly increased risk of AIDS related mortality. Conclusion: Longitudinal trajectory analysis of multiple immune indicators can be employed to guide targeted interventions among vulnerable populations in clinical practice.

Association of tirofiban treatment with outcomes following endovascular therapy in cardioembolic stroke: insights from the RESCUE BT randomized trial.

BACKGROUND AND PURPOSE: The efficacy and safety of tirofiban in endovascular therapy for cardioembolic ischemic stroke patients remain controversial. This study aimed to evaluate the role of intravenous tirofiban before endovascular therapy in cardioembolic stroke. METHODS: This post hoc analysis utilized data from the RESCUE BT (Endovascular Treatment With versus Without Tirofiban for Patients with Large Vessel Occlusion Stroke) trial, which was an investigator-initiated, randomized, double-blind, placebo-controlled trial. Participants were randomized to receive either tirofiban or a placebo in a 1:1 ratio before undergoing endovascular therapy. The study included patients aged 18 years or older, presenting with occlusion of the internal carotid artery or middle cerebral artery (MCA) M1/M2 within 24 h of the last known well time, and with a stroke etiology of cardioembolism. The primary efficacy outcome was global disability at 90 days, assessed using the modified Rankin Scale (mRS). The safety outcome included symptomatic intracranial hemorrhage (sICH) within 48 h and mortality within 90 days. RESULTS: A total of 406 cardioembolic stroke patients were included in this study, with 212 assigned to the tirofiban group and 194 assigned to the placebo group. Tirofiban treatment did not correlate with a favorable shift towards a lower 90-day mRS score (adjusted common odds ratio [OR], 0.91; 95% CI 0.64-1.3; p = 0.617). However, the tirofiban group had a significantly higher risk of symptomatic intracranial hemorrhage (sICH) within 48 h (adjusted OR, 3.26; 95% CI 1.4-7.57; p = 0.006) compared to the placebo group. The adjusted odds ratio (aOR) for mortality within 90 days was 1.48 (95% CI 0.88-2.52; p = 0.143). CONCLUSIONS: Tirofiban treatment was not associated with a lower level of disability and increased the incidence of sICH after endovascular therapy in cardioembolic stroke patients.

Association between creatinine to body weight ratio and all-cause mortality: a cohort study of NHANES.

Research on the relationship between the weight-adjusted skeletal muscle mass index and all-cause mortality is rare, and even rarer is the relationship between the creatinine/body weight (Cre/BW) ratio and all-cause mortality. Therefore, this study aimed to investigate the relationship between the Cre/BW ratio and mortality in individuals with normal renal function. This prospective study used data from the National Health and Nutrition Examination Survey (NHANES) database. A Cox hazard model was used to analyze the relationship between the Cre/BW ratio and mortality risk. In total, 45,459 participants were included, of which 49.97% were women, with an average age of 45.68 ± 18.08 years. The incidence of all-cause mortality was 10.9% among these participants during the median (interquartile range) follow-up of 9.6 (5.2, 14.2) years. After adjusting for all covariates, a U-shaped relationship was found between the Cre/BW ratio and all-cause mortality (P for nonlinearity <0.001), with the lowest risk observed at Cre/BW ratios (×100) between 0.821 and 0.987. In the threshold effect analysis, the Cre/BW ratio (×100) had a threshold value of 0.96. When the Cre/BW ratio (×100) was <0.96, all-cause mortality was negatively associated with the Cre/BW ratio (×100) (0.63 (0.41, 0.97)). In contrast, when the Cre/BW ratio (×100) was ≥0.96, the higher Cre/BW ratio was associated with a greater hazard ratio of all-cause mortality (1.67 (1.41, 1.97)). In conclusion, we report a U-shaped relationship between the Cre/BW ratio and all-cause mortality. Controlling the Cre/BW ratio within a certain range may reduce the risk of all-cause mortality.

Association between human herpes simplex virus and periodontitis: results from the continuous National Health and Nutrition Examination Survey 2009-2014.

BACKGROUND: Periodontitis is a common chronic oral disease which seriously affects people's quality of life. Although human herpes simplex virus (HSV) is also found in periodontal lesions, the association between HSV infection and periodontitis is unclear. METHODS: The National Health and Nutrition Examination Survey (NHANES) data for 2009-2010, 2011-2012 and 2013-2014 was combined, and the association between HSV infection and periodontitis in the general population and particular subgroups was investigated through weighted multi-logistic analyses. RESULTS: There were 4,733 participants aged 30-50 years old with clinically assessed periodontitis concurrent with HSV infection. In general analysis, after adjusted for covariates, both HSV-1 (OR = 1.09, P < 0.001) and HSV-2 (OR = 1.06, P = 0.030) infection was significantly associated with periodontitis. In subgroup analyses, compared with patients without HSV infection, patients with HSV-1( +) & HSV-2( +) and HSV-1( +) & HSV-2(-) infection showed higher risk of periodontitis in all subgroups (OR = 1.15, OR = 1.09, P < 0.001), while patients with HSV-1(-) & HSV-2( +) infection showed higher risk of and periodontitis only in the subgroup of people aged 40-50 years (OR = 1.10, P = 0.032) and the Mexican-American subgroup (OR = 1.35, P = 0.042). When only severe periodontitis is considered, HSV infection was associated with periodontitis, no matter the patient was infected with either of the virus or both. CONCLUSIONS: HSV-1 infection was significantly associated with periodontitis and severe periodontitis, while HSV-2 infection was associated with severe periodontitis, and periodontitis in 40-50-year-olds and Mexican-Americans.

Collateral Status Modification of the Association Between Blood Pressure Variation Within 72 Hours After Endovascular Treatment and Clinical Outcome in Acute Ischemic Stroke: A Retrospective Cohort Study.

Background: Blood pressure variation and collateral status have been reported to be associated with clinical outcome in patients with acute ischemic stroke who received endovascular treatment; however, the relationship between blood pressure variation within 72 hours after EVT and clinical outcome in different collateral status remains unclear. Methods: Acute ischemic stroke patients due to large vessel occlusion with EVT were retrospectively enrolled. We classified participants into poor collateral (ASITN/SIR grade <2) and good collateral subgroups (ASITN/SIR grade ≥2). The primary outcome was unfavorable neurological outcome defined as a 3-month modified Rankin Scale (mRS) score ≥2. The interactive effect was tested to determine the influence of collateral status on the association between BP variation and clinical outcome. Results: A total of 545 patients were included. The poor collateral subgroup was detected in 198 patients with an average age of 70.2 years. The association between BP variation and primary outcome did not differ under different collateral status (P for interaction >0.05). However, the association between the mean and coefficient of variation (CV) values of DBP and 3-month mortality was significantly discrepant under different collateral status (P for interaction <0.05). In the good collateral subgroup, higher mean DBP was associated with a lower risk of 3-month mortality (OR 0.95, 95% CI 0.91-1, P = 0.033) compared with the poor subgroup (OR 1.04, 95% CI 0.97-1.1, P = 0.286). In addition, a higher CV of DBP was associated with a higher risk of 3-month mortality (OR 1.24, 95% CI 1.13-1.36, P < 0.01) compared with poor status (OR 1.08, 95% CI 0.94-1.23, P=0.275). Conclusion: For patients who received EVT with good collateral status, increased CV of DBP was significantly associated with higher 3-month mortality, while higher mean DBP within 72 h after EVT was associated with a decrease in 3-month mortality.

Assessing the influencing factors of out-of-pocket costs on tuberculosis in Sichuan Province: a cross-sectional study.

BACKGROUND: Although diagnosis and treatment services for tuberculosis (TB) are provided free of charge in most countries, direct non-medical and indirect costs due to absenteeism, also place a significant burden on patients and their families. Sichuan Province has the second highest incidence of TB in China, with an incidence of approximately 100 cases per 100 000 people. However, there are limited research on out-of-pocket expenditure (OOPE) and its influencing factors in TB patients in Sichuan Province. METHODS: A retrospective cross-sectional study was conducted on TB patients in designated medical institutions for TB in Sichuan Province from 2017-2021. A face-to-face questionnaire was conducted to obtain the information related to hospitalization of patients, and the multi-level regression model was used to analyse the factors that influence OOPE and total out-of-pocket expenditure (TOOPE) of TB patients. RESULTS: A total of 2644 patients were investigated, and 74.24% of TB patients and their families experienced catastrophic total costs due to TB. The median total cost was 9223.37 CNY (1429.98 USD), in which the median direct and indirect costs of TB patients were 10185.00 CNY (1579.07 USD) and 2400.00 CNY (372.09 USD), respectively, and indirect costs contributed to 43% of total costs. The median OOPE and TOOPE costs were 6024.00 CNY (933.95 USD) and 11890.50 CNY (1843.49 USD), respectively. OOPE and TOOPE had common influencing factors including whether the patient's family had four or more members, a history of hospitalization, combination with other types of TB, the number of visits before diagnosis, and co-occurrence with chronic disease. CONCLUSIONS: The OOPE and TOOPE for TB patients and their families in Sichuan Province are still heavy. In the long run, it is necessary to strengthen education and awareness campaigns on TB related knowledge, disseminate basic medical knowledge to the public, improve healthcare-seeking behavior, and enhance the healthcare infrastructure to improve the accuracy of TB diagnosis and reduce the significant OOPE and TOOPE faced by TB patients and their families in Sichuan Province.

Vitamin D3 affects the gut microbiota in an LPS-stimulated systemic inflammation mouse model.

Although gut dysbiosis contributes to systemic inflammation, the counteractive effect of systemic inflammation on gut microbiota is unknown. Vitamin D may exert anti-inflammatory effects against systemic inflammation, but its regulation of the gut microbiota is poorly understood. In this study, mice were intraperitoneally injected with lipopolysaccharide (LPS) to create a systemic inflammation model and received vitamin D3 treatment orally for 18 continuous days. Then, body weight, morphological changes in the colon epithelium, and gut microbiota (n = 3) were evaluated. We verified that LPS stimulation caused inflammatory changes in the colon epithelium, which could be obviously attenuated by vitamin D3 treatment (10 µg/kg/day) in mice. Then, 16S rRNA gene sequencing of the gut microbiota first revealed that LPS stimulation induced a large number of operational taxonomic units, and vitamin D3 treatment reduced the number. In addition, vitamin D3 had distinctive effects on the community structure of the gut microbiota, which was obviously changed after LPS stimulation. However, neither LPS nor vitamin D3 affected the alpha and beta diversity of the gut microbiota. Furthermore, statistical analysis of differential microorganisms showed that the relative abundance of microorganisms in the phylum Spirochaetes decreased, the family Micrococcaceae increased, the genus [Eubacterium]_brachy_group decreased, the genus Pseudarthrobacter increased, and the species Clostridiales_bacterium_CIEAF_020 decreased under LPS stimulation, but vitamin D3 treatment significantly reversed the LPS-induced changes in the relative abundance of these microorganisms. In conclusion, vitamin D3 treatment affected the gut microbiota and alleviated inflammatory changes in the colon epithelium in the LPS-stimulated systemic inflammation mouse model.

Cyclin-dependent kinase 5 negatively regulates antiviral immune response by disrupting myeloid differentiation primary response protein 88 self-association.

As a member of the pattern recognition receptors (PRRs) involving in the innate immune system, Toll-like receptors (TLRs) can sense a wide range of microbial pathogens and combat infections by producing antimicrobial products, inflammatory cytokines, and chemokines. All TLRs, with the exception of TLR3, activate a signalling cascade via the myeloid differentiation primary response gene 88 (MyD88). Therefore, the activation of MyD88-dependent signalling pathway must be finely controlled. Herein, we identified that cyclin-dependent kinase 5 (CDK5) negatively regulated TLR-MyD88 signalling pathway by targeting MyD88. Overexpression of CDK5 reduced the production of interferons (IFNs), while a deficiency in CDK5 increased the expression of IFNs in response to vesicular stomatitis virus (VSV) infection. Mechanistically, CDK5 suppressed the formation of MyD88 homodimers, resulting in the attenuated production of IFNs induced by VSV infection. Surprisingly, its kinase activity does not play a role in this process. Therefore, CDK5 can act as an internal regulator to prevent excessive production of IFNs by restricting TLR-MyD88-induced activation of antiviral innate immunity in A549 cells.

Upregulation of Microglial Sirt6 and Inhibition of Microglial Activation by Vitamin D3 in Lipopolysaccharide-stimulated Mice and BV-2 Cells.

Vitamin D3 may suppress microglial activation and neuroinflammation, which play a central role in the pathophysiology of many neurological disorders. Sirt6 can remove histone 3 lysine 9 acetylation (H3K9ac) to repress expression of pathological genes and produce anti-inflammatory effects. However, whether vitamin D3 upregulates microglial Sirt6 to exert its protective effects against microglial activation and neuroinflammation is unclear. The effects of lower, normal, and higher dosages (1, 10 and 100 µg/kg/day) of vitamin D3 on behavioral and neuromorphological changes, brain inflammatory factors, Sirt6 and H3K9ac levels, and microglial Sirt6 distribution in hippocampus were evaluated in lipopolysaccharide (LPS)-stimulated mice. In addition, the effects of vitamin D3 on inflammatory factors, reactive oxygen species, Sirt6, and H3K9ac were confirmed in LPS-stimulated BV-2 cells. We verified that vitamin D3 ameliorated the impaired sociability of LPS-stimulated mice by three-chamber test. In addition, vitamin D3 upregulated brain Sirt6 generation, reduced H3K9ac levels and inhibited generation of brain inflammatory factors. Moreover, vitamin D3 promoted microglial Sirt6 distribution and attenuated microglia displaying an activated morphology in the hippocampus of LPS-stimulated mice. Similarly, vitamin D3 upregulated Sirt6 generation and intensity, reduced H3K9ac levels, and inhibited the inflammatory activation of LPS-stimulated BV-2 cells. In conclusion, vitamin D3 may upregulate microglial Sirt6 to reduce H3K9ac and inhibit microglial activation, thereby antagonizing neuroinflammation.

Antiretroviral treatment interruption and resumption within 16 weeks among HIV-positive adults in Jinan, China: a retrospective cohort study.

Background: Treatment interruption has been found to increase the risk of opportunistic infections and death among HIV-positive adults, posing a challenge to fully realizing antiretroviral therapy (ART). However, it has been observed that short-term interruption (<16 weeks) was not associated with significant increases in adverse clinical events. There remains a dearth of evidence concerning the interruption and resumption of ART after short-term discontinuation in China. Methods: HIV-positive adults who initiated ART in Jinan between 2004 and 2020 were included in this study. We defined ART interruption as more than 30 consecutive days off ART and used Cox regression to identify predictors of interruption. ART resumption was defined as a return to ART care within 16 weeks following discontinuation, and logistic regression was used to identify barriers. Results: A total of 2,506 participants were eligible. Most of them were male [2,382 (95%)] and homosexual [2,109 (84%)], with a median age of 31 (IQR: 26-40) years old. Of all participants, 312 (12.5%) experienced a treatment interruption, and the incidence rate of interruption was 3.2 (95% CI: 2.8-3.6) per 100 person-years. A higher risk of discontinuation was observed among unemployed individuals [adjusted hazard ratio (aHR): 1.45, 95% CI: 1.14-1.85], with a lower education level (aHR: 1.39, 95% CI: 1.06-1.82), those with delayed ART initiation (aHR: 1.43, 95% CI: 1.10-1.85), receiving Alafenamide Fumarate Tablets at ART initiation (aHR: 5.19, 95% CI: 3.29-8.21). About half of the interrupters resumed ART within 16 weeks, and participants who delayed ART initiation, missed the last CD4 test before the interruption and received the "LPV/r+NRTIs" regimen before the interruption were more likely to discontinue treatment for the long term. Conclusion: Antiretroviral treatment interruption remains relatively prevalent among HIV-positive adults in Jinan, China, and assessing socioeconomic status at treatment initiation will help address this issue. While almost half of the interrupters returned to care within 16 weeks, further focused measures are necessary to reduce long-term interruptions and maximize the resumption of care as soon as possible to avoid adverse clinical events.

Major intracranial arterial stenosis influence association between baseline blood pressure and clinical outcomes after thrombolysis in ischemic stroke patients.

BACKGROUND: This study aimed to investigate the relationship between baseline blood pressure (BP) and clinical outcomes after thrombolysis for acute ischemic stroke (AIS) in different intracranial arterial stenosis subgroups. METHODS: AIS patients from multicenter with intravenous thrombolysis were retrospectively enrolled from January 2013 to December 2021. We categorized participants into severe (≥ 70%) and nonsevere (< 70%) stenosis of major intracranial arteries subgroups. The primary outcome was unfavorable functional outcome defined as 3-month modified Rankin Scale (mRS) ≥2. The association coefficients between baseline BP and functional outcomes were estimated in general linear regression model. The interactive effect was tested to determine the influence of intracranial arterial stenosis on the association between BP and clinical outcomes. RESULTS: A total of 329 patients were included. Severe subgroup was detected in 151 patients with average age of 70.5. Association between baseline diastolic BP (DBP) and unfavorable functional outcome in intracranial artery stenosis subgroups was significantly different (p for interaction < .05). In nonsevere subgroup, higher baseline DBP was associated with higher risk of unfavorable outcome (OR 1.11, 95% CI 1.03 to 1.20, p = .009) compared with severe subgroup (OR 1.02, 95% CI 0.97 to 1.08, p = .341). Besides, intracranial artery stenosis also modified association between baseline systolic BP (SBP) and 3-month death (p for interaction < .05). In severe subgroup, higher baseline SBP was associated with decreased 3-month death risk (OR 0.88, 95% CI 0.78 to 1, p = .044) compared with nonsevere subgroup (OR 1, 95% CI 0.93 to 1.07, p = .908). CONCLUSIONS: The major intracranial artery state modulates association between baseline BP and 3-month clinical outcomes after intravenous thrombolysis.

Chalcone Derivative CX258 Suppresses Colorectal Cancer via Inhibiting the TOP2A/Wnt/ß-Catenin Signaling.

The deregulation in the Wnt/ß-catenin signaling pathway is associated with many human cancers, particularly colorectal cancer (CRC) and, therefore, represents a promising target for drug development. We have screened over 300 semisynthetic and natural compounds using a Wnt reporter assay and identified a family of novel chalcone derivatives (CXs) that inhibited Wnt signaling and CRC cell proliferation. Among them, we selected CX258 for further in vitro and in vivo study to investigate the molecular mechanisms. We found that CX258 significantly inhibited ß-catenin expression and nuclear translocation, inducing cell cycle arrest at the G2/M phase in CRC cells. Additionally, CX258 reduced the expression of DNA Topoisomerase II alpha (TOP2A) in CRC cells. Moreover, knocking down TOP2A by siRNAs inhibited the Wnt/ß-catenin signaling pathway, a finding suggesting that CX258 inhibited Wnt/ß-catenin signaling and CRC cell proliferation at least partially by modulating TOP2A. Further studies showed that CDK1 that interacts with TOP2A was significantly reduced after TOP2A knockdown. We demonstrated that CX258 significantly inhibited DLD-1 CRC cell xenografts in SCID mice. In summary, we identified CX258 as a promising candidate for colorectal cancer treatment by targeting the TOP2A/Wnt/ß-catenin signaling pathway.

Effect of tracheal intubation on postoperative complications in patients with pulmonary hypertension combined with non-cardiothoracic, non-obstetric surgery.

Endotracheal intubation can be associated with certain complications in certain group of patients. However, the relationship between endotracheal intubation and postoperative complications is unclear in patients with pulmonary hypertension (PHTN). This study evaluated the relationship between endotracheal intubation and postoperative complications in non-cardiothoracic and non-obstetric surgery patients with PHTN. A secondhand analysis of non-cardiothoracic, non-obstetric procedures was performed on patients with PHTN between 2007 and 2013 in a hospital at the University of Washington. Multivariable logistic regression analyses were used to calculate the adjusted odds ratios to estimate the association between anesthesia and 30-day postoperative complications. Interaction and stratified analyses were conducted according to the American Society of Anesthesiologists score (ASA), smoking, hypertension, and open surgical approach. A total of 573 patients were included in this study, and the mean age was 60.3; 54% were male. In a multivariate regression model for patients with non-cardiothoracic, non-obstetric surgery combined with PHTN, the risk of 30-day postoperative complications was higher in the tracheal intubation group than in patients with non-intubated anesthesia after adjusting for potential covariates (adjusted odds ratio = 2.47; 95% CI, 1.28-4.78). However, there was no significant difference in postoperative mortality between these groups. Statistical analysis showed no interaction between the variables of tracheal intubation and 30-day postoperative complications. In this study, we found that tracheal intubation anesthesia is associated with increased risk of 30-day postoperative complications in PHTN patients undergoing non-cardiothoracic, non-obstetric surgery. Further studies are needed to confirm our findings.

Association between C-reactive protein-albumin ratio and overall survival in Parkinson's disease using publicly available data: A retrospective cohort study.

Background: At present, many studies have confirmed that inflammation plays a central role in Parkinson's disease (PD). The inflammatory index is related to the prognosis of the disease, but a single inflammatory index has some limitations. The C-reactive protein-albumin ratio (CAR) is a better marker of inflammation or nutritional status than C-reactive protein (CRP) or albumin (Alb), but there is limited study on the association between CAR and the overall survival (OS) of PD. Object: To study the association between CAR and OS in PD patients. Methods: All of these data were obtained from the Dryad Digital Repository, based on which we conducted a secondary analysis. The study was conducted by the Department of Neurology, the National Regional Center for Neurological Disorders, and the National Hospital of Utano study between March 2004 to November 2007. The final analytic sample included 235 PD patients with the outcome of survival or all-cause death from the study registration to the endpoint. In this study, univariate and multivariate COX regression analyses were used to calculate the adjusted hazard ratio (HR), with a 95% confidence interval (CI). In addition, the association between CAR and OS in PD patients was explored by Kaplan-Meier curve and subgroup analysis. Results: This study included 235 PD patients with an average age of 62.25 years, including 135 females and 100 males, and 45 died during the follow-up period. CAR was associated with gender, modified Hoehn-Yahr stages (mH-Y), and Mini-Mental State Examination (MMSE) of PD patients. In the COX multivariate regression model, after adjusting the age, gender, PD duration, mH-Y, MMSE, and the non-steroidal anti-inflammatory drugs, CAR was found to be associated with the OS in PD (HR = 1.54, 95% CI = 1.01-2.34, p = 0.044). Subgroup analysis showed that the subgroup did not play an interactive role in the association between the prognosis of patients with CAR and PD (p for interaction >0.05), and the results remained stable. Conclusions: The all-cause mortality of PD patients with a high level of CAR is higher, which indicates that the poor overall survival of PD patients is associated with the increase of CAR. The CAR may be a reliable prognostic biomarker for PD patients.

Study on the extension of the dynamic benchmark system of per capita carbon emissions in China's county.

County is the center of China's socio-economic development and the key node for urban-rural integration. Also, the county is an important carrier for promoting urban and rural green development. Improving green and low-carbon development capabilities and formulating county-level low-carbon standards will play a significant role in promoting China's new people-oriented urbanization and rural revitalization. Although there have been extensive studies on low-carbon benchmarks, over half of the benchmarks tend to ignore the development stage of the evaluated region and its needs. When the region's economy reaches a certain level, constraints from low-carbon targets may limit the local development process. This study firstly allocated county carbon intensity reduction targets (CIRT) by considering the differences in county carbon reduction capacity and responsibility. Secondly, a dynamic benchmark system of per capita carbon emissions (PCCE) in counties in China is constructed. Finally, we took Changxing County in Zhejiang Province as a research case to verify the dynamic benchmark of PCCE. According to the carbon intensity target reduction rate (CITRR), China's counties can be divided into three categories: low carbon emissions reduction capability-responsible counties (L-CERCRC), medium carbon emissions reduction capability-responsible counties (M-CERCRC), and high carbon emissions reduction capability-responsible counties (H-CERCRC). The results show that (1) due to the national CO2 emission reduction target in 2030, the carbon intensity will be 60% lower than in 2005, the CITRR for China's 1510 counties range from 8.36 to 137.83%; the average CITRR is 48.40%. (2) Changxing County's CITRR is 57.71%, which belongs to the H-CERCRC. The PCCE of Changxing County will be much higher than the benchmark when the carbon peak is reached in the future. (3) For reaching the aiming benchmark, Changxing County is suggested to adjust its relevant influencing factors of PCCE for converting local's PCCE reaching to the benchmark within a certain time period. The dynamic benchmark system for PCCE in China's counties established in this study is economically sensitive, which not only takes the differences of counties into account, but also meets the needs of counties' diverse development form stages. This system provides counties a few coordinated directions which can improve the local's economic development and reduce greenhouse gas (GHGs) emissions through the development progress.