Injectable Hydrogels Based on Hyaluronic Acid and Gelatin Combined with Salvianolic Acid B and Vascular Endothelial Growth Factor for Treatment of Traumatic Brain Injury in Mice.

Traumatic brain injury (TBI) leads to structural damage in the brain, and is one of the major causes of disability and death in the world. Herein, we developed a composite injectable hydrogel (HA/Gel) composed of hyaluronic acid (HA) and gelatin (Gel), loaded with vascular endothelial growth factor (VEGF) and salvianolic acid B (SAB) for treatment of TBI. The HA/Gel hydrogels were formed by the coupling of phenol-rich tyramine-modified HA (HA-TA) and tyramine-modified Gel (Gel-TA) catalyzed by horseradish peroxidase (HRP) in the presence of hydrogen peroxide (H2O2). SEM results showed that HA/Gel hydrogel had a porous structure. Rheological test results showed that the hydrogel possessed appropriate rheological properties, and UV spectrophotometry results showed that the hydrogel exhibited excellent SAB release performance. The results of LIVE/DEAD staining, CCK-8 and Phalloidin/DAPI fluorescence staining showed that the HA/Gel hydrogel possessed good cell biocompatibility. Moreover, the hydrogels loaded with SAB and VEGF (HA/Gel/SAB/VEGF) could effectively promote the proliferation of bone marrow mesenchymal stem cells (BMSCs). In addition, the results of H&E staining, CD31 and α-SMA immunofluorescence staining showed that the HA/Gel/SAB/VEGF hydrogel possessed good in vivo biocompatibility and pro-angiogenic ability. Furthermore, immunohistochemical results showed that the injection of HA/Gel/SAB/VEGF hydrogel to the injury site could effectively reduce the volume of defective tissues in traumatic brain injured mice. Our results suggest that the injection of HA/Gel hydrogel loaded with SAB and VEGF might provide a new approach for therapeutic brain tissue repair after traumatic brain injury.

Nomogram-based geometric and hemodynamic parameters for predicting the growth of small untreated intracranial aneurysms.

Previous studies have shown that the growth status of intracranial aneurysms (IAs) predisposes to rupture. This study aimed to construct a nomogram for predicting the growth of small IAs based on geometric and hemodynamic parameters. We retrospectively collected the baseline and follow-up angiographic images (CTA/ MRA) of 96 small untreated saccular IAs, created patient-specific vascular models and performed computational fluid dynamics (CFD) simulations. Geometric and hemodynamic parameters were calculated. A stepwise Cox proportional hazards regression analysis was employed to construct a nomogram. IAs were stratified into low-, intermediate-, and high-risk groups based on the total points from the nomogram. Receiver operating characteristic (ROC) analysis, calibration curves, decision curve analysis (DCA) and Kaplan-Meier curves were evaluated for internal validation. In total, 30 untreated saccular IAs were grown (31.3%; 95%CI 21.8%-40.7%). The PHASES, ELAPSS, and UIATS performed poorly in distinguishing growth status. Hypertension (hazard ratio [HR] 4.26, 95%CI 1.61-11.28; P = 0.004), nonsphericity index (95%CI 4.10-25.26; P = 0.003), max relative residence time (HR 1.01, 95%CI 1.00-1.01; P = 0.032) were independently related to the growth status. A nomogram was constructed with the above predictors and achieved a satisfactory prediction in the validation cohort. The log-rank test showed significant discrimination among the Kaplan-Meier curves of different risk groups in the training and validation cohorts. A nomogram consisting of geometric and hemodynamic parameters presented an accurate prediction for the growth status of small IAs and achieved risk stratification. It showed higher predictive efficacy than the assessment tools.

Effect of Physical Exercise on Executive Functions Using the Emotional Stroop Task in Perimenopausal Women: A Pilot Study.

Exercise has beneficial effects on emotional cognitive control for the majority of the population. However, the impact of exercise on cognitive processes in perimenopausal women remains unclear. Therefore, this study investigated the effect of aerobic exercise on the cognitive processes of perimenopausal women using an emotional Stroop task (EST). METHOD: A quasi-experimental pilot study was conducted involving 14 perimenopausal women (Peri-MG) and 13 healthy young women (YG) who completed an EST before and after an aerobic cycling exercise. Mixed-effects models for repeated measures were used to analyze reaction times (RTs) and error rates (ERs) during emotional word processing (positive, negative, and neutral) for both groups. RESULTS: Compared with the YG, the Peri-MG showed significantly shortened RTs for positive and negative emotions (p < 0.05) post-exercise, but not for neutral words. In addition, the Peri-MG exhibited significantly increased ERs for negative words at baseline compared with the YG (p < 0.05), but this difference was not observed during the post-exercise test. CONCLUSION: The findings suggest that aerobic exercise can enhance executive control performance in perimenopausal women. The Peri-MG exhibited marked behavioral plasticity in the form of reduced bias to salient cues that were significantly more sensitive to alterations due to exercise. This new evidence enhances the understanding of emotional vulnerability and beneficial susceptibility to exercise in perimenopausal women.

A detection model of testis-derived circular RNAs in serum for predicting testicular sperm retrieval rate in non-obstructive azoospermia patients.

BACKGROUND: Microdissection testicular sperm extraction is an effective method to retrieve sperm from non-obstructive azoospermia patients. However, its successful rate is less than 50%. OBJECTIVES: To identify the predictive value of circular RNAs in serum for sperm retrieval rate in non-obstructive azoospermia patients. MATERIALS AND METHODS: 180 non-obstructive azoospermia patients were recruited in this study, including 84 individuals with successful sperm retrieval and 96 individuals with failed sperm retrieval. Our study contained two phases. First, 20 patients, selected from the 180 patients, were included in screening cohort. In this cohort, the top 20 circular RNAs from our previous testicular circRNA profiles were verified between successful and failed sperm retrieval groups using real-time polymerase chain reaction. Six circular RNAs with the most significantly different expressions were selected for further verification. Second, the 180 patients were included as discovery cohort to verify the six circular RNAs. Circular RNAs were extracted from serum in each participant. Logistic regression analysis was further performed to identify the predictive value and the area under the curve analysis was used to evaluate diagnostic efficiency, sensitivity, and specificity. RESULTS: Six circular RNAs including hsa_circ_0058058, hsa_circ_0008045, hsa_circ_0084789, hsa_circ_0000550, hsa_circ_0007422, and hsa_circ_0004099 showed aberrant expressions between the successful and failed sperm retrieval group. In addition, both single-circular RNA panels and multi-circular RNA panels were finally verified to be significant in predicting sperm retrieval rate. Notably, multi-circular RNAs panels demonstrated better predictive abilities compared with single-circRNA panels, and the combined panel of six-circular RNAs (risk score = 1.094×hsa_circ_0058058+0.697×hsa_circ_0008045+0.718×hsa_circ_0084789-0.591×hsa_circ_0000550-0.435×hsa_circ_0007422-1.017×hsa_circ_0004099-1.561) exhibited the best predictive ability in the present study with an AUC of 0.977, a sensitivity of 91.7% and a specificity of 86.5%. A higher risk score indicated a higher risk of failure in sperm retrieval. DISCUSSION AND CONCLUSION: Our study was the first to report that testis-derived circular RNAs in serum have the ability to predict sperm retrieval rate in non-obstructive azoospermia patients, whether it is a single-circular RNA or a combination of multi-circular RNAs.

Exosomes-Mediated Signaling Pathway: A New Direction for Treatment of Organ Ischemia-Reperfusion Injury.

Ischemia reperfusion (I/R) is a common pathological process which occurs mostly in organs like the heart, brain, kidney, and lung. The injury caused by I/R gradually becomes one of the main causes of fatal diseases, which is an urgent clinical problem to be solved. Although great progress has been made in therapeutic methods, including surgical, drug, gene therapy, and transplant therapy for I/R injury, the development of effective methods to cure the injury remains a worldwide challenge. In recent years, exosomes have attracted much attention for their important roles in immune response, antigen presentation, cell migration, cell differentiation, and tumor invasion. Meanwhile, exosomes have been shown to have great potential in the treatment of I/R injury in organs. The study of the exosome-mediated signaling pathway can not only help to reveal the mechanism behind exosomes promoting reperfusion injury recovery, but also provide a theoretical basis for the clinical application of exosomes. Here, we review the research progress in utilizing various exosomes from different cell types to promote the healing of I/R injury, focusing on the classical signaling pathways such as PI3K/Akt, NF-κB, Nrf2, PTEN, Wnt, MAPK, toll-like receptor, and AMPK. The results suggest that exosomes regulate these signaling pathways to reduce oxidative stress, regulate immune responses, decrease the expression of inflammatory cytokines, and promote tissue repair, making exosomes a competitive emerging vector for treating I/R damage in organs.

Exploring the provision, efficiency and improvements of urban green spaces on accessibility at the metropolitan scale.

Accurately assessing urban green space (UGS) accessibility and proposing effective and specific proposals for UGS provision improvement accordingly is vital to urban development. Taking the metropolitan of Shanghai, China as the study site, this study first assessed its UGS provision by improved multiple step floating catchment area methods and multiple indexes, including UGS accessibility, theoretical capacity, potential demand, and traffic supply. Second, it investigated the impacts on citywide UGS accessibility justice for each UGS by comparing Gini index differences of citywide UGS accessibility between the conditions when exist and non-exist for each UGS. Third, it used ternary plots to explore the influence mechanism of the factors of UGS theoretical capacity, potential demand, and traffic supply on accessibility, and introduced an RGB color triangle to spatially and simultaneously display the effects of these three factors on accessibility for each UGS in Shanghai. Fourth, it assessed and classified the UGS provision efficiency for accessibility according to the relationships among the theoretical capacity, potential demand, and traffic supply factors by 3D scatter plot. Fifth, it proposed specific types and priorities of requirement for UGS improvement according to its impact on citywide UGS accessibility justice and the effect of its theoretical capacity factor on UGS accessibility. The findings showed that UGS accessibility and its three factors in Shanghai were correlative and had a spatial clustering trend in central city areas. The majority of UGSs showed positive impact on citywide accessibility justice, which went up with the values of accessibility and the three factors. Most UGSs were dominated by theoretical capacity power. The UGS provision efficiency was relatively good for most UGSs, which had relatively well-matched conditions and demands. The improvement requirements for UGSs on accessibility investigated in this study will improve UGS provision.

Prevalence and prognosis of acute ischemic stroke coexisting with unruptured intracranial aneurysms.

Objectives: The prevalence of unruptured intracranial aneurysms (UIAs) in the acute ischemic stroke (AIS) cohort is probably higher than in the general population. This study investigated the prevalence of UIAs in AIS patients and the management risk and prognosis when treating AIS. Methods: From January 2020 to January 2023, we conducted a single-center retrospective study at Tianjin Huanhu Hospital. Each patient underwent both brain MRI and MRA/CTA to diagnose AIS and UIAs. Clinical, radiologic, and therapeutic data during hospitalization and prognosis were analyzed. Propensity-score matching (PSM) was performed to evaluate the risk of in-hospital adverse events, unfavorable outcomes at discharge when receiving post-stroke treatment and stroke recurrence. Results: In all, 2,181 AIS patients were included, of whom 270 had UIAs (12.4%; 95%CI 11.0-13.8%). From the unmatched and matched cohort, the incidence of in-hospital adverse events and unfavorable outcomes at discharge in patients with UIAs were not significantly different; the risk of stroke recurrence was significantly higher in patients with UIAs than in those without (unmatched: aHR, 1.71 [1.08-2.70]; matched: aHR, 2.55 [1.16-5.58]). Multivariable Cox regression models showed that aneurysm size and the presence of homoregional infarction associated with higher risk of recurrence (unmatched: aHR, 1.31 [1.21-1.41] and aHR, 3.50 [1.52-8.10]; matched: aHR, 1.28 [1.18-1.40]; p < 0.001 and aHR, 3.71 [1.12-12.34]). Conclusion: The UIAs may not increase the risk of in-hospital adverse events and unfavorable outcomes at discharge in receiving post-stroke treatment, but it may associated with a high risk of stroke recurrence.

A comparative study of biological properties of three root canal sealers.

OBJECTIVES: The aim of this study was to evaluate the effects of Hiflow with other two kinds of root canal sealers on the biological behavior of stem cells from the apical papilla (SCAP), the influence on inflammatory cytokines release and its antibacterial effects. MATERIALS AND METHODS: Material extracts of Hiflow, iRoot SP, and AH Plus were prepared. Then, SCAP was incubated with extracts. The effects were evaluated by CCK-8, wound healing assay, ALP staining, alizarin red staining, and qRT-PCR. Meanwhile, polymorphonuclears (PMNs) and monocytes were isolated and treated with extracts for 4 h and 24 h respectively. Cell viability was analyzed by Annexin-V/PI double staining flow cytometry. The effects on the release of cytokines were observed by ELISA. The antibacterial effects of different sealers were tested against three kinds of bacteria found in chronic apical periodontitis. RESULTS: A series of results of SCAP showed that Hiflow and iRoot SP could promote cell proliferation, migration, and osteogenesis (p < 0.05). Although Hiflow was associated with greater cell apoptosis and necrosis when incubated with PMNs and monocytes (p < 0.05), it had an approximate release of anti-inflammatory cytokines with iRoot SP, which was higher than AH plus (p < 0.05). The co-culture showed that Hiflow and iRoot SP inhibited the colony formation of F. nucleatum (p < 0.05). However, both sealers had no obvious antibacterial effect on E. faecalis and P. gingivalis (p > 0.05). CONCLUSIONS: In summary, Hiflow and iRoot SP both had positive biological stimulus on SCAP. Meanwhile, Hiflow showed a better induction on anti-inflammatory cytokines over the others. All the properties mentioned above and its antibacterial effect of F. nucleatum promise Hiflow a bright application prospect in endodontic uses. CLINICAL RELEVANCE: References for clinical work to use BC Sealer Hiflow as a good biological root canal sealer.

Complete genome sequence of Proteiniborus sp. MB09-C3, isolated from the feces of the black soldier fly larvae.

Here, we report the complete genome sequence of Proteiniborus sp. MB09-C3 (= BCRC 81405), isolated from the feces of black soldier fly (Hermetia illucens) larvae. The genome of strain MB09-C3 was selected for further species delineation and comparative genomic analysis.

Recent Advances in Biodegradable and Biocompatible Synthetic Polymers Used in Skin Wound Healing.

The treatment of skin wounds caused by trauma and pathophysiological disorders has been a growing healthcare challenge, posing a great economic burden worldwide. The use of appropriate wound dressings can help to facilitate the repair and healing rate of defective skin. Natural polymer biomaterials such as collagen and hyaluronic acid with excellent biocompatibility have been shown to promote wound healing and the restoration of skin. However, the low mechanical properties and fast degradation rate have limited their applications. Skin wound dressings based on biodegradable and biocompatible synthetic polymers can not only overcome the shortcomings of natural polymer biomaterials but also possess favorable properties for applications in the treatment of skin wounds. Herein, we listed several biodegradable and biocompatible synthetic polymers used as wound dressing materials, such as PVA, PCL, PLA, PLGA, PU, and PEO/PEG, focusing on their composition, fabrication techniques, and functions promoting wound healing. Additionally, the future development prospects of synthetic biodegradable polymer-based wound dressings are put forward. Our review aims to provide new insights for the further development of wound dressings using synthetic biodegradable polymers.

Clinical characteristics of spontaneous intracranial basal ganglia hemorrhage and risk factors for hematoma expansion in the plateaus of China.

Background and purpose: The clinical features of intracranial cerebral hemorrhage (ICH) and the risk factors for hematoma expansion (HE) have been extensively studied. However, few studies have been performed in patients who live on a plateau. The natural habituation and genetic adaptation have resulted in differences in disease characteristics. The purpose of this study was to investigate the differences and consistency of clinical and imaging characteristics of patients in the plateaus of China compared with the plains, and to analyze the risk factors for HE of intracranial hemorrhage in the plateau patients. Methods: From January 2020 to August 2022, we undertook a retrospective analysis of 479 patients with first-episode spontaneous intracranial basal ganglia hemorrhage in Tianjin and Xining City. The clinical and radiologic data during hospitalization were analyzed. Univariate and multivariate logistic regression analyzes were used to assess the risk factors for HE. Results: HE occurred in 31 plateau (36.0%) and 53 plain (24.2%) ICH patients, and HE was more likely to occur in the plateau patients compared with the plain (p = 0.037). The NCCT images of plateau patients also showed heterogeneity of hematoma imaging signs, and the incidence of blend signs (23.3% vs. 11.0%, p = 0.043) and black hole signs (24.4% vs. 13.2%, p = 0.018) was significantly higher than in the plain. Baseline hematoma volume, black hole sign, island sign, blend sign, and PLT and HB level were associated with HE in the plateau. Baseline hematoma volume and the heterogeneity of hematoma imaging signs were independent predictors of HE in both the plain and plateau. Conclusion: Compared with the plain, ICH patients in the plateau were more prone to HE. The patients showed the same heterogeneous signs on the NCCT images as in the plain, and also had predictive value for HE.

Investigation of the antibacterial effect, osteogenic activity, and tracing properties of hydroxyapatite co-doped with Tb3+ and Zn2.

Hydroxyapatite (HA) is a biomimetic biomaterial that has been widely used in bone repair for many years. However, the increased risk of infection after surgery and long-time tracing for the material distribution and degradation during bone reconstruction remain challenges in the clinic. Zinc (Zn) is considered as an indispensable microelement for humans and is characterized with antibacterial action and osteogenic activity. Terbium (Tb), a rare-earth element, emits stable fluorescence under ultraviolet light. Here, Tb3+/Zn2+ co-doped hydroxyapatite (HA:Tb/Zn) was prepared to synchronously realize the antibacterial effect, osteogenic activity, and long-time tracing property. We found that HA:Tb/Zn had a strong antibacterial effect on both Gram-positive and Gram-negative clinical infectious bacteria, as well as improved osteogenic activity. HA:Tb/Zn also displayed stable green fluorescence in vitro and in vivo, which indicated great potential for recognizing the material changes during the bone reconstruction process. The combination of the ternary functions is of great significance to control the overuse of antibiotics and realize long-time tracing, and provide a versatile design on biomaterials in bone repair.

The landscape of endodontic education research area: A bibliometric analysis.

OBJECTIVES: Educational research is essential for rationalizing curriculum design, improving evaluation systems, and updating teaching content. This bibliometric study aimed at analyzing the characteristics of publications relevant to endodontic education, thus forming a comprehensive scope of this research area. METHODS: The search was conducted in the Web of Science Core Collection database in May 2022. Knowledge units of the included publications, such as year of publication, journal, country/institution/author, keywords, and highly cited articles/references, were analyzed. RESULTS: The United States ranked first in the number of articles with a total of 17 articles. The majority of included articles were published in Journal of Dental Education (n = 25), International Endodontic Journal (n = 21), and European Journal of Dental Education (n = 14). The top 3 most frequent keywords were Endodontics, Education, and Root canal treatment. The main topic in endodontic education were curriculum, preclinical education, educational technology, and continuing education. CONCLUSION: Forming a full scope of the endodontic research area, this bibliomertic analysis can help mine the hot topic, predict the frontiers in the field and provide the data necessary to determine the direction of research, rationalize resource allocation, and formulate policy.

The application and perspective of hyperbaric oxygen therapy in acute ischemic stroke: From the bench to a starter?

Stroke has become a significant cause of death and disability globally. Along with the transition of the world's aging population, the incidence of acute ischemic stroke is increasing year by year. Even with effective treatment modalities, patients are not guaranteed to have a good prognosis. The treatment model combining intravenous thrombolysis/endovascular therapy and neuroprotection is gradually being recognized. After the clinical translation of pharmacological neuroprotective agents failed, non-pharmacological physical neuroprotective agents have rekindled hope. We performed a literature review using the National Center for Biotechnology Information (NCBI) PubMed database for studies that focused on the application of hyperbaric oxygen therapy in acute ischemic stroke. In this review, we present the history and mechanisms of hyperbaric oxygen therapy, focusing on the current status, outcomes, current challenges, perspective, safety, and complications of the application of hyperbaric oxygen in animal experiments and human clinical trials. Hyperbaric oxygen therapy, a non-pharmacological treatment, can improve the oxygenation level at the ischemic lesions in increased dissolved oxygen and oxygen diffusion radius to achieve salvage of neurological function, giving a new meaning to acute ischemic stroke.

Natural products from traditional medicine as promising agents targeting at different stages of oral biofilm development.

Oral cavity is an ideal habitat for more than 1,000 species of microorganisms. The diverse oral microbes form biofilms over the hard and soft tissues in the oral cavity, affecting the oral ecological balance and the development of oral diseases, such as caries, apical periodontitis, and periodontitis. Currently, antibiotics are the primary agents against infectious diseases; however, the emergence of drug resistance and the disruption of oral microecology have challenged their applications. The discovery of new antibiotic-independent agents is a promising strategy against biofilm-induced infections. Natural products from traditional medicine have shown potential antibiofilm activities in the oral cavity with high safety, cost-effectiveness, and minimal adverse drug reactions. Aiming to highlight the importance and functions of natural products from traditional medicine against oral biofilms, here we summarized and discussed the antibiofilm effects of natural products targeting at different stages of the biofilm formation process, including adhesion, proliferation, maturation, and dispersion, and their effects on multi-species biofilms. The perspective of antibiofilm agents for oral infectious diseases to restore the balance of oral microecology is also discussed.

The Arginine Biosynthesis Pathway of Candida albicans Regulates Its Cross-Kingdom Interaction with Actinomyces viscosus to Promote Root Caries.

The cross-kingdom interactions between Candida albicans and Actinomyces viscosus play critical roles in root caries. However, the key pathway by which C. albicans regulates its interactions with A. viscosus is unclear. Here, we first employed 39 volunteers with root caries and 37 caries-free volunteers, and found that the abundances of C. albicans and A. viscosus were significantly increased in the individuals with root caries and showed a strong positive correlation. Their dual-species combination synergistically promoted biofilm formation and root caries in rats. The arginine biosynthesis pathway of C. albicans was significantly upregulated in dual-species biofilms and dental plaques from another 10 root caries volunteers compared with the 10 caries-free volunteers. The exogenous addition of arginine increased the cariogenicity of the dual-species biofilm. The C. albicans ARG4, a key gene from the arginine biosynthesis pathway, null mutant failed to promote dual-species biofilm formation and root caries in rats; however, the addition of arginine restored its synergistic actions with A. viscosus. Our results identified the critical roles of the C. albicans arginine biosynthesis pathway in its cross-kingdom interactions with A. viscosus for the first time and indicated that targeting this pathway was a practical way to treat root caries caused by multiple species. IMPORTANCE Root caries is a critical problem that threatens the oral health of the elderly population. Our results identified the essential roles of the C. albicans arginine biosynthesis pathway in its cross-kingdom interactions with A. viscosus in root caries for the first time and indicated that targeting this pathway was a practical way to treat root caries caused by multiple species.

Exposure to melamine and its derivatives in Chinese adults: The cumulative risk assessment and the effect on routine blood parameters.

Melamine (MEL) and its derivatives, ammeline (AMN), ammelide (AMD), cyanuric acid (CYA) are widely existed in environmental media. Animal studies have reported the cumulative risk assessment (CRA) of simultaneous exposure to MEL and its derivatives and explored the associations between exposure and routine blood parameters. Such information is largely unknown in human studies. In this study, we detected the urinary concentrations of MEL and its derivatives in 239 Chinese adults to conduct the CRA by evaluating their hazard quotients (HQ) and hazard Index (HI), and also explored the possible associations between exposure and measured routine blood parameters in study population. The detectable frequencies of MEL, AMN, AMD and CYA were 96.65%, 41.00%, 97.91% and 97.07%, respectively. The median values of creatinine (Cr)-adjusted MEL, AMN, AMD, CYA and the total concentrations of MEL and its derivatives (∑MEL) were 11.41 µg/g Cr, not detected (ND), 2.64 µg/g Cr, 15.30 µg/g Cr, 35.02 µg/g Cr, respectively. There were 9 (3.77%) participants with estimated daily intakes (EDIs) of CYA exceeding the tolerable daily intake (TDI) of 2500 ng/kg bw/day, and 12 (5.02%) participants with HI of ∑MEL exposure exceeding 1 based on the strictest TDI value. Urinary concentrations of MEL and its derivatives were positively associated with specific routine blood parameters, including hematocrit, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin concentration, mean corpuscular hemoglobin, white blood cell, neutrophil count (P < 0.05). Meanwhile, exposure to MEL and its derivatives increased the risk of red blood cell abnormality (P < 0.05). Our study is the first study to provide evidence-based data on the CRA of exposure to MEL and its derivatives in Chinese adults, and to propose a possible association between such exposure and routine blood parameters in human.

Anterior Circulation Acute Ischemic Stroke in the Plateau of China: Risk Factors and Clinical Characteristics.

Background and Purpose: Acute ischemic stroke has a high incidence in the plateau of China. It has unique characteristics compared to the plains, and the specific relationship with altitude has not yet been appreciated. This study aimed to investigate the specificity of the plateau's anterior circulation acute ischemic stroke in China. Methods: To retrospectively collect clinical data of patients with first-episode acute ischemic stroke in the anterior circulation in Tianjin and Xining city. The differences in clinical presentation, laboratory, and imaging examinations were compared. Results: Patients at high altitudes showed a significant trend toward lower age (61.0 ± 10.2 vs. 64.8 ± 8.1, P = 0.010) and had a history of dyslipidemia, higher levels of inflammatory markers, erythrocytosis, and alcohol abuse. The main manifestations were higher diastolic blood pressure (85.5 ± 14.0 mmHg vs. 76.8 ± 11.6 mmHg, P < 0.001), triglycerides [2.0 (1.8) mmol/L vs. 1.3 (0.9) mmol/L, P < 0.001], CRP [4.7 (4.4) mg/L vs. 2.1 (1.9) mg/L, P < 0.001], homocysteine levels [14.5 (11.7) µmol/L vs. 11.2 (5.2) µmol/L, P < 0.001]; larger infarct volume [3.5 (4.8) cm3 vs. 9.0 (6.9) cm3, P < 0.001] and worse prognosis. Patients at high altitudes had higher atherosclerotic indexes in cIMT and plaque than those in plains. Conclusions: The natural habituation and genetic adaptation of people to the particular geo-climatic environment of the plateau have resulted in significant differences in disease characteristics. Patients with the anterior circulation acute ischemic stroke in the plateau show more unfavorable clinical manifestations and prognosis. This study provides a preliminary interpretation of the effects of altitude and suggests developing preventive and therapeutic protocol measures that are more appropriate for the plateau of China.

Various potentially toxic element tolerances in different rice genotypes correlate with distinct physiological responses and alterations in DNA methylation.

Potentially toxic elements (PTEs) are harmful to plant growth and reduce crop productivity. In this work, we studied three rice genotypes (T-35, RZ-1, and RZ-2) to quantify the diverse PTE effects and tolerances by examining morphology, physiology, and DNA methylation patterns. Morphological results showed that T-35 exhibits the highest tolerance to all studied PTE stressors (Cu, Cd, Cr). Physiological responses under PTE stresses confirmed earlier findings, where T-35 showed a higher potassium (K+) content and more peroxidase (POD) accumulation in the roots than the other two rice genotypes. The differences in PTE tolerance levels observed among the three rice genotypes were also associated with variations in the heavy metal transportation (HMT) gene expression level. Moreover, methylation-sensitive blotting analysis of the selected genes showed that the DNA methylation changes occurring due to PTE treatments are mainly CHG hypomethylation in T-35 but hypermethylation in RZ-1 and RZ-2. Our results demonstrate a tight relationship among physiological response, expression levels of the HMT genes, and DNA methylation pattern under PTEs stresses. It is also indicated that plants use generic mechanisms to tolerate stresses; however, different genotypes employ different combinations of such tactics to confer tolerance, which results in diverse PTE stress tolerances. These findings shed light on the PTE stresses tolerance mechanism and help direct future breeding activities in rice.