Highly concentrated collagen/chondroitin sulfate scaffold with platelet-rich plasma promotes bone-exposed wound healing in porcine.

In the case of wounds with exposed bone, it is essential to provide not only scaffolds with sufficient mechanical strength for protection, but also environments that are conducive to the regeneration of tissues and blood vessels. Despite the excellent biocompatibility and biodegradability of collagen and chondroitin sulfate, they display poor mechanical strength and rapid degradation rates. In contrast to previous methodologies that augmented the mechanical properties of biomaterials through the incorporation of additional substances, this investigation exclusively enhanced the mechanical strength of collagen/chondroitin sulfate scaffolds by modulating collagen concentrations. Furthermore, platelet-rich plasma (PRP) was employed to establish optimal conditions for vascular and tissue regeneration at the wound site. High-concentration collagen/chondroitin sulfate (H C-S) scaffolds were synthesized using high-speed centrifugation and combined with PRP, and their effects on endothelial cell proliferation were assessed. A porcine model of bone-exposed wounds was developed to investigate the healing effects and mechanisms. The experimental results indicated that scaffolds with increased collagen concentration significantly enhanced both tensile and compressive moduli. The combination of H C-S scaffolds with PRP markedly promoted endothelial cell proliferation. In vivo experiments demonstrated that this combination significantly accelerated the healing of porcine bone-exposed wounds and promoted vascular regeneration. This represents a promising strategy for promoting tissue regeneration that is worthy of further exploration and clinical application.

Hypomagnesemia is Associated with the Skull Computed Tomography Black Hole Sign in Patients with Spontaneous Intracerebral Hemorrhage.

OBJECTIVES: The evaluation of hypomagnesemia's significance in predicting the presence of the black hole sign in patients with intracranial hemorrhage is currently under investigation. METHODS: The study included 261 patients with cerebral hemorrhage who underwent initial skull computed tomography within 24 hours of admission. Sixty-nine patients (26.4%) exhibited hypomagnesemia in the initial laboratory examinations. The black hole sign was observed in 123 patients (referred to as the black hole sign group, which includes patients with and without hypomagnesemia), while the remaining 138 patients (nonblack hole sign group) did not exhibit this feature. The values of hypomagnesemia were assessed through multivariable logistic regression analyses. RESULTS: The black hole sign occurred in 45 of the 69 (65.2%) patients with hypomagnesemia, and in 78 of the 192 (40.6%) patients without hypomagnesemia. In the black hole sign group, hypomagnesemia was observed in 45 patients (36.6%). However, only 24 patients (19.5%) from the normal magnesium concentration group exhibited hypomagnesemia. The sensitivity, specificity, and positive and negative predictive values of hypomagnesemia for predicting the black hole sign were 69.9%, 82.5%, 36.6%, and 82.8%, respectively. The odds ratios for hypomagnesemia, smoking history, and hypokalemia in predicting the presence of the black hole sign were 2.74, 1.971, and 1.629, correspondingly. CONCLUSIONS: The presence of hypomagnesemia may serve as a predictive factor for the black hole sign and rebleeding in patients with intracerebral hemorrhage, thereby providing valuable guidance for clinical treatment.

Trefoil factor 1 (TFF1) reduces cerebral edema and gastric mucosal injury by regulating the EGFR/Src/FAK pathway in an intracerebral hemorrhage rat model.

The destruction of the blood-brain barrier and damage to the gastrointestinal mucosa after intracerebral hemorrhage (ICH) are important reasons for its high disability and mortality rates. However, the exact etiology is not yet clear. In addition, there are currently no effective treatments for improving cerebral edema and gastric mucosal damage after ICH. Trefoil factor 1 (TFF1) is a secretory protein that plays a crucial role in maintaining the integrity and barrier function of the gastric mucosa, and it has been reported to have a protective effect on brain damage induced by various causes. This study utilized a rat model of ICH induced by type IV collagenase was utilized, and intervened with recombinant TFF1 protein from an external institute to investigate the protective mechanisms of TFF1 against brain edema and gastric mucosal damage after ICH. The results demonstrated that TFF1 alleviated the neurological function and gastric mucosal damage in the rat model of ICH induced by type IV collagenase. TFF1 may ensure the integrity of the blood-brain and gastric mucosal barriers by regulating the EGFR (epidermal growth factor receptor)/Src (non-receptor tyrosine kinase)/FAK (focal adhesion kinase) pathway. Clearly, the disruption of the blood-brain barrier and the destruction of the gastric mucosal barrier are key pathological features of ICH, and TFF1 can improve the progression of blood-brain barrier and gastric mucosal barrier disruption in ICH by regulating the EGFR/Src/FAK pathway. Therefore, TFF1 may be a potential target for the treatment of ICH.

Effect of Reinforcement Bar on Trueness of Printed Titanium Kennedy I Removable Partial Denture Frameworks by Selective Laser Melting.

OBJECTIVE: The addition of reinforcement bars is a commonly used method to improve the fabrication trueness of selective laser melting removable partial denture alloy frameworks. However, the effects of different reinforcement bar designs on the trueness of the entire framework remain unclear. This study investigated the trueness of removable partial denture frameworks of pure titanium fabricated by selective laser melting under different reinforcement bar settings. METHOD: A virtual framework was designed based on the Kennedy Class I partially edentulous model using computer-aided design software. Frameworks with different reinforcement bar settings (Ti-A without reinforcement bar, Ti-B with a single horizontal bar joining the lingual bar, Ti-C with two more bars at the anterior region, Ti-D with another horizontal bar at the anterior region, and Ti-E with one more bar at the posterior region, n = 5) were printed using pure titanium powder using a direct metal laser melting machine. The fabricated frameworks were scanned, and their fabrication trueness was compared with the designed virtual framework using one-way ANOVA. RESULTS: The overall mean discrepancies for Ti-A, Ti-B, Ti-C, Ti-D, and Ti-E were 0.111, 0.047, 0.073, 0.068, and 0.047 mm, respectively. For the group of Ti-A set with no reinforcement bars, larger discrepancies were observed compared with the other four groups (P < .05). Groups Ti-B and Ti-E showed better trueness of the RPI clasps, rests, and distal ends (P < .05). CONCLUSIONS: Adding reinforcement bars improved the printing trueness of the pure titanium frameworks, and different settings resulted in various degrees of improvement. Setting a single reinforcement bar to join the lingual bar or an additional reinforcement bar at the distal end significantly enhanced the printing trueness of the RPI clasps, rests, and distal ends.

Comparison of selective laser melting and stereolithography etching templates for guided endodontics.

Background: With the increasing application of guided endodontics to treat complex root canal treatment, the entire process of root canal treatment has become more precise, reducing damage to tooth structure and improving success rates. However, due to the limitations of the operating space, the use of guided endodontic templates in posterior root canal treatment is less common. This study aims to compare the accuracy and reliability of selective laser melting (SLM) and traditional stereolithography etching (SLA) guided endodontic templates for posterior root canals, providing better treatment strategies for posterior root canal treatment. Methods: The teeth were randomly assigned to either SLM or SLA group. Preoperative cone-beam computed tomography (CBCT) and a three-dimensional (3D) scanner were used to establish the 3D root canal system and the accurate occlusal models of the teeth. The virtual access to the canal access was designed using Mimics 19.0 and 3-Matic 11.0. The endodontic access was performed based on either SLM or SLA templates. The accuracy of endodontic preparation was measured in three-dimensions by calculating deviations from planned accesses. The template height and tooth substance loss rates in each group were measured. Results: SLM-guided templates have a low average deviation at the entry point and apical portion of the bur of total posterior teeth (including premolars and molars) and individual molars (P < 0.05). Moreover, there was a significant difference in angular deviations and height of template in total posterior teeth and individual molars (P < 0.05). The mean substance loss rate of the SLA group was slightly greater than that of the SLM group, but the difference was not statistically (P > 0.05). Conclusions: SLM-guided endodontics provides a more predictable and precise location of root canal orifice for the treatment of posterior teeth.

Synaptic vesicle protein 2A mitigates parthanatos via apoptosis-inducing factor in a rat model of pharmacoresistant epilepsy.

AIMS: Synaptic vesicle protein 2A (SV2A) is a unique therapeutic target for pharmacoresistant epilepsy (PRE). As seizure-induced neuronal programmed death, parthanatos was rarely reported in PRE. Apoptosis-inducing factor (AIF), which has been implicated in parthanatos, shares a common cytoprotective function with SV2A. We aimed to investigate whether parthanatos participates in PRE and is mitigated by SV2A via AIF. METHODS: An intraperitoneal injection of lithium chloride-pilocarpine was used to establish an epileptic rat model, and phenytoin and phenobarbital sodium were utilized to select PRE and pharmacosensitive rats. The expression of SV2A was manipulated via lentivirus delivery into the hippocampus. Video surveillance was used to assess epileptic ethology. Biochemical tests were employed to test hippocampal tissues following a successful SV2A infection. Molecular dynamic calculations were used to simulate the interaction between SV2A and AIF. RESULTS: Parthanatos core index, PARP1, PAR, nuclear AIF and MIF, γ-H2AX, and TUNEL staining were all increased in PRE. SV2A is bound to AIF to form a stable complex, successfully inhibiting AIF and MIF nuclear translocation and parthanatos and consequently mitigating spontaneous recurrent seizures in PRE. Moreover, parthanatos deteriorated after the SV2A reduction. SIGNIFICANCE: SV2A protected hippocampal neurons and mitigated epileptic seizures by inhibiting parthanatos via binding to AIF in PRE.

Ultrasound­guided erector spinae plane block in posterior lumbar surgery (Review).

The erector spinae plane block (ESPB) is a novel fascial planar block technique, which is used to reduce postoperative pain in several surgical procedures, including breast, thoracic, spine and hip surgery. Due to its recognizable anatomy and low complication rate, the application of ESPB has been significantly increased. However, it is rarely used in clinical practice for postoperative analgesia after posterior lumbar spine surgery, while the choice of adjuvant drugs, block levels and drug doses remain controversial. Based on the current literature review, ropivacaine and dexmedetomidine could be considered as the best available drug combination. The present review aimed to analyze the currently available clinical evidence and summarize the benefits and challenges of ESPB in spinal surgery, thus providing novel insights into the application of ESPB in the postoperative management of posterior lumbar surgery.

Relationship between socioeconomic status and hypertension incidence among adults in southwest China: a population-based cohort study.

PURPOSE: To investigate the correlation between socioeconomic status (SES) and the incidence of hypertension among adults aged 18 or above in southwest China. METHODS: A multistage proportional stratified cluster sampling method was employed to recruited 9280 adult residents from 12 counties in southwest China, with all participants in the cohort tracked from 2016 to 2020. The questionnaire survey gathered information on demographics, lifestyle habits, and household income. The physical exam recorded height, weight, and blood pressure. Biochemical tests measured cholesterol levels. The chi-square test was employed to assess the statistical differences among categorical variables, while the Cox proportional hazards regression model was applied to evaluate the association between socioeconomic status (SES) and the incidence of hypertension. RESULTS: The finally effective sample size for the cohort study was 3546 participants, after excluding 5734 people who met the exclusion criteria. Adults in the highest household income group had a significantly lower risk of hypertension compared to those in the lowest income group (HR = 0.636, 95% CI: 0.478-0.845). Besides, when compared to individuals in the illiterate population, the risk of hypertension among adults with elementary school, junior high school, senior high school and associate degree educational level decreased respectively by 34.4% (HR = 0.656, 95%CI: 0.533-0.807), 44.9% (HR = 0.551, 95%CI: 0.436-0.697), 44.9% (HR = 0.551, 95%CI: 0.405-0.750), 46.1% (HR = 0.539, 95%CI: 0. 340-0.854). After conducting a thorough analysis of socioeconomic status, compared with individuals with a score of 6 or less, the risk of hypertension in participants with scores of 8, 10, 11, 12, and greater than 12 decreased respectively by 23.9% (HR = 0.761, 95%CI: 0.598-0.969), 29.7% (HR = 0.703, 95%CI: 0.538-0.919), 34.0% (HR = 0.660, 95%CI: 0.492-0.885), 34.3% (HR = 0.657, 95%CI: 0.447-0.967), 43.9% (HR = 0.561, 95%CI: 0.409-0.769). CONCLUSION: The findings indicate a negative correlation between socioeconomic status and hypertension incidence among adults in southwest China, suggesting that individuals with higher socioeconomic status are less likely to develop hypertension.

Cystatin C Attenuates Perihematomal Secondary Brain Injury by Inhibiting the Cathepsin B/NLRP3 Signaling Pathway in a Rat Model of Intracerebral Hemorrhage.

Secondary brain injury (SBI) is a noticeable contributor to the high mortality and morbidity rates associated with intracerebral hemorrhage (ICH), and effective treatment options remain limited. Cystatin C (CysC) emerges as a novel candidate for SBI intervention. The therapeutic effects and underlying mechanisms of CysC in mitigating SBI following ICH were explored in the current research. An in vivo ICH rat model was established by injecting autologous blood into the right caudate nucleus. Western blotting (WB) was utilized to assess the levels of CysC, cathepsin B (CTSB), and the NLRP3 inflammasome. Subsequently, the ICH rat model was treated with exogenous CysC supplementation or CysC knockdown plasmids. Various parameters, including Evans blue (EB) extravasation, brain water content, and neurological function in rats, were examined. RT-qPCR and WB were employed to determine the expression levels of CTSB and the NLRP3 inflammasome. The co-expression of CTSB, CysC, and NLRP3 inflammasome with GFAP, NeuN, and Iba1 was assessed through double-labeled immunofluorescence. The interaction between CysC and CTSB was investigated using double-labeled immunofluorescence and co-immunoprecipitation. The findings revealed an elevation of CysC expression level, particularly at 24 h after ICH. Exogenous CysC supplementation alleviated severe brain edema, neurological deficit scores, and EB extravasation induced by ICH. Conversely, CysC knockdown produced opposite effects. The expression levels of CTSB and the NLRP3 inflammasome were significantly risen following ICH, and exogenous CysC supplement attenuated their expression levels. Double-labeled immunofluorescence illustrated that CysC, CTSB, and the NLRP3 inflammasome were predominantly expressed in microglial cells, and the interaction between CysC and CTSB was evidenced. CysC exhibited potential in ameliorating SBI following ICH via effectively suppressing the activation of the NLRP3 inflammasome mediated by CTSB specifically in microglial cells. These findings underscore the prospective therapeutic efficacy of CysC in the treatment of ICH-induced complications.

Rosiglitazone Promotes Microglial Distribution via Activation of PPARγ and CD36 in the ICH Rat Model.

OBJECTIVES: Intracerebral hemorrhage (ICH) is a serious public health problem with high mortality and morbidity. The current study aims to investigate the effects of rosiglitazone on the microglial distribution and the expression of PPARγ and CD36 in the ICH rat model. METHODS NEW: Sprague-Dawley male rats (n=116) were randomly divided into four groups: control, ICH, rosiglitazone, and PPARγ antagonist (GW9662). Hematoxylin-eosin staining was used to observe the brain edema in the ICH rat model. The effect of rosiglitazone on the expression of OX-42, a microglial marker, was evaluated by immunohistochemistry. Immunohistochemistry, quantitative real-time PCR, and western blot were utilized to assess the role of rosiglitazone in the expression of PPARγ and CD36. RESULTS: ICH rats exhibited a remarkable brain edema at 72 h. OX-42 expression was significantly increased in brain tissues of ICH rats. Rosiglitazone remarkably promoted the OX-42 expression in ICH rats, whereas GW9662 suppressed OX-42 expression. In addition, immunohistochemistry analysis showed that rosiglitazone markedly enhanced the expression of PPARγ and CD36 in brain tissues around the hematoma in ICH rats, while GW9662 inhibited their expression in ICH rats. Moreover, rosiglitazone significantly promoted the mRNA and protein expression of PPARγ and CD36 in the brain tissues of ICH rats, while GW9662 showed the opposite trend. CONCLUSION: Rosiglitazone may improve microglial distribution via promoting the expression of PPARγ and CD36 around the hematoma in the ICH rat model, which may provide effective therapeutic targets for the treatment of ICH.

Influence of 3D printed surface micro-structures on molding performance and dental bonding properties of zirconia.

OBJECTIVES: To investigate the influence of the 3D printed micro-structured surfaces on the bond strength of zirconia to resin cement. METHODS: Zirconia specimens were divided into five groups based on manufacturing technique and surface preparation: (1) milled zirconia (M group); (2) milled zirconia airborne abraded (MA group); (3) printed zirconia (M group); (4) printed zirconia airborne abraded (PA group); and (5) printed zirconia with micro-structured surface (PM group). The surface morphology, cross-sectional morphology, and elemental composition were observed using a scanning electron microscope (SEM). Surface roughness was measured using a laser scanning confocal microscope (SLCM). Shear bond strength (SBS) was measured using a universal testing machine after bonding resin cement (n = 10). The failure modes of the bonded fracture interfaces were observed and counted using a stereomicroscope and a SEM. In addition, boundary dimensional accuracy (n = 10) and micro-structural dimensional accuracy (n = 20) of printed zirconia specimens with micro-structured surfaces were measured using digital calipers and Fiji software. The crystalline phase changes before and after surface treatment were investigated using X-ray diffractometry. Data was analysed using one-way ANOVA and Tukey HSD post-hoc tests (α = 0.05). RESULT: The surface micro-structures of the PM group had regular morphology and no obvious defects. The surface roughness results showed that the PM group had higher Sa (42.21±1.38 um) and Ra (21.25±1.80 um) values than the other four groups (p < 0.001). The SBS test showed that the bond strength of the PM group reached 11.23 ± 0.66 MPa, which was 55.97% (p < 0.001) higher than that of the P group (7.20 ± 1.14 MPa). The boundary dimensional accuracy of the PM group was proficient (diameter: 99.63 ± 0.31%, thickness: 98.05 ± 1.12%), and the actual fabrication dimensions of the hexagonal micro-structures reached 77.45%-80.01% of the original design. The micro-structured surface did not affect the crystalline phase of zirconia. CONCLUSIONS: The current study illustrates that 3D-printed microstructured surfaces effectively improve the bond strength of zirconia to resin cements. CLINICAL SIGNIFICANCE: With the advantage of 3D printing, this study provides a new idea for improving the bonding properties of zirconia.

Increased Cyclic Adenosine Monophosphate Responsive Element is Closely Associated with the Pathogenesis of Drug-resistant Epilepsy.

BACKGROUND: Drug-resistant epilepsy (DRE) is a refractory neurological disorder. There is ample evidence that suggest that γ-aminobutyric acid-a (GABAA) receptors could be one of the mechanisms responsible for the development of drug resistance in epilepsy. It is also known that the cAMP response element binding protein (CREB) plays a possible key role in the transcriptional regulation of GABAA. OBJECTIVE: This study explores the role of CREB in the development of DRE and the effect of CREB on GABA-related receptors in DRE. METHODS: The CREB expression was increased or decreased in the hippocampus of normal rats by lentiviral transfection, who then underwent the lithium-pilocarpine-induced epilepsy model. Phenobarbital (PB) sodium and carbamazepine (CBZ) were used to select a drug-resistant epileptic model. The expression levels of GABAA receptor α1, ß2, and γ2 subunits and CREB protein were measured in the rat hippocampus by western blot and fluorescent quantitative PCR. RESULTS: The frequency and duration of seizures increased in the overexpression group compared to that in the control group. In addition, the severity, frequency, and duration of seizures decreased in the group with decreased expression. The hippocampus analysis of the expression levels of the CREB protein and CREB mRNA yielded similar findings. Altering the CREB protein expression in the rat hippocampus could negatively regulate the expression and transcript levels of GABAA receptors α1, ß2, and γ2, suggesting that CREB may serve as a potential target for the development of treatment protocols and drugs for epilepsy. CONCLUSION: Our study shows that enhanced CREB expression promotes the development of DRE and negatively regulates GABAA receptor levels and that the inhibition of CREB expression may reduce the incidence of DRE.

Influence of intraoral scanning duration on data accuracy.

STATEMENT OF PROBLEM: The use of intraoral scanners (IOSs) correlates with clinical outcome and patient satisfaction. While the accuracy of IOSs has been well evaluated, studies on the effect of scanning duration on data accuracy are limited. PURPOSE: The purpose of this in vitro study was to investigate the relationship between different scanning durations and the accuracy of the scanned data. MATERIAL AND METHODS: Two experienced operators used the same intraoral scanner (TRIOS 3; 3Shape A/S) to scan a gypsum cast, but with 5 different scanning durations (30 seconds, 60 seconds, 90 seconds, 120 seconds, and 180 seconds), and the trueness of the scanned data was assessed. Ten scans for each duration group were performed, and all the acquired data were evaluated for precision analysis. In addition, each scanned complete arch cast was divided into anterior and posterior regions at the canine teeth, and the 3-way ANOVA test was used to assess the scanning trueness and precision of the scanned anterior and posterior dental arch. RESULTS: The intraoral scanning results between the 2 operators were highly consistent. The data of the 30-second group showed the lowest trueness and precision (P<.001), whereas no significant difference was found among the other groups (P>.05). The trueness and precision of the scanning data in the posterior region was inferior to that in the anterior region (P<.001). CONCLUSIONS: The duration time of the intraoral scanning (ranging from 60 seconds to 180 seconds) did not influence the accuracy of the acquired data, while excessively rapid scanning adversely affected accuracy.

Inhibitory effect and mechanism of Rosiglitazone on M1 type polarization of central microglia in intracerebral hemorrhage mice based on JNK/STAT3 signaling pathway.

BACKGROUND: Intracerebral hemorrhage (ICH) seriously threatens the health of people. In addition, microglia M1 polarization was confirmed to be involved in the progression of ICH. Rosiglitazone was able to be used as an antidiabetic agent, which could activate PPAR-γ, and PPAR-γ was reported to inhibit inflammation in microglia. However, the detailed function of Rosiglitazone in ICH remains unclear. METHODS: In vivo and in vitro experiments were used to test the function of Rosiglitazone in ICH. In addition, RT-qPCR and western blot were performed to evaluate the mRNA and protein level of PPAR-γ, respectively. Immunofluorescence staining was performed to detect the levels of CD206 and CD86, and ELISA was used to measure the levels of pro-inflammatory cytokines. RESULTS: PPAR-γ was downregulated in ICH mice, whereas p-JNK and p-STAT3 were upregulated. Thrombin notably downregulated the level of PPAR-γ in BV2 cells, whereas Rosiglitazone partially reversed this phenomenon. In addition, Rosiglitazone markedly reversed thrombin-induced microglia M1 polarization. Consistently, thrombin-induced inflammatory response in BV2 cells was abolished in the presence of Rosiglitazone. SP600125 (JNK/STAT3 inhibitor) greatly reversed thrombin-induced M1 polarization in microglia, and GW9662 abolished the effect of SP600125. Meanwhile, Rosiglitazone could inactivate JNK/STAT3 pathway through the upregulation of PPAR-γ. Furthermore, Rosiglitazone notably alleviated the symptom of ICH in vivo through inhibiting the apoptosis and mediating PPAR-γ/JNK/STAT3 axis. CONCLUSION: Rosiglitazone could attenuate the inflammation in ICH through inhibiting microglia M1 polarization. Thus, our research would shed now lights on exploring new therapeutic strategies against ICH.

Case report: Inspiration from a rare fatal heart perforation after percutaneous vertebroplasty.

The principal benefit of employing percutaneous vertebroplasty (PVP) for managing osteoporotic vertebral compression fractures lies in its capacity to facilitate early mobilization in elderly patients, thereby effectively avoiding the potential catastrophic complications associated with prolonged bedridden states. However, bone cement leakage, as the most common complication of PVP, may have fatal consequences. Here, we report a case involving an 85-year-old male patient with L1 vertebral compression fracture who underwent PVP at our hospital and was discharged on the same day of the surgical intervention. Subsequently, the patient experienced symptoms of chest tightness and palpitations. Cardiac ultrasound examination revealed pericardial effusion, while pulmonary computed tomographic angiography (CTA) demonstrated a strip high-density shadow in the right ventricular area. Finally, it was determined that the perforation of the right ventricular wall was caused by bone cement embolism. Through this comprehensive case report, we aim to deepen the understanding of orthopedic doctors on the importance of preventing bone cement leakage.

Human Expansion-Induced Biodiversity Crisis over Asia from 2000 to 2020.

Asia stands out as a priority for urgent biodiversity conservation due to its large protected areas (PAs) and threatened species. Since the 21st century, both the highlands and lowlands of Asia have been experiencing the dramatic human expansion. However, the threat degree of human expansion to biodiversity is poorly understood. Here, the threat degree of human expansion to biodiversity over 2000 to 2020 in Asia at the continental (Asia), national (48 Asian countries), and hotspot (6,502 Asian terrestrial PAs established before 2000) scales is investigated by integrating multiple large-scale data. The results show that human expansion poses widespread threat to biodiversity in Asia, especially in Southeast Asia, with Malaysia, Cambodia, and Vietnam having the largest threat degrees (∼1.5 to 1.7 times of the Asian average level). Human expansion in highlands induces higher threats to biodiversity than that in lowlands in one-third Asian countries (most Southeast Asian countries). The regions with threats to biodiversity are present in ∼75% terrestrial PAs (including 4,866 PAs in 26 countries), and human expansion in PAs triggers higher threat degrees to biodiversity than that in non-PAs. Our findings provide novel insight for the Sustainable Development Goal 15 (SDG-15 Life on Land) and suggest that human expansion in Southeast Asian countries and PAs might hinder the realization of SDG-15. To reduce the threat degree, Asian developing countries should accelerate economic transformation, and the developed countries in the world should reduce the demands for commodity trade in Southeast Asian countries (i.e., trade leading to the loss of wildlife habitats) to alleviate human expansion, especially in PAs and highlands.

Hemolysin from Aeromonas hydrophila enhances the host's serum enzyme activity and regulates transcriptional responses in the spleen of Cyprinus rubrofuscus.

Aeromonas hydrophila is a conditional pathogen impacting public hygiene and safety. Hemolysin is a virulence factor of Aeromonas hydrophila that causes erythrocyte hemolysis, yet its transcriptional response to Cyprinus rubrofuscus remains unknown. Our investigation confirmed the hemolysis of hemolysin from A. hydrophila. Serum enzyme activity was evaluated weekly after C. rubrofuscus were immunized with hemolysin Ahh1. The results showed that the hemolysin enhances the serum superoxide dismutase (SOD), lysozyme (LZM), and catalase (CAT) activity, which reached a maximum on day 14. To elucidate the molecular interaction between hemolysin from A. hydrophila and the host, we performed transcriptome sequencing on the spleen of C. rubrofuscus 14 days post hemolysin infection. The total number of clean reads was 41.37 Gb, resulting in 79,832 unigenes with an N50 length of 1863 bp. There were 1982 significantly differentially expressed genes (DEGs), including 1083 upregulated genes and 899 downregulated genes. Transcript levels of the genes, such as LA6BL, CD2, and NLRC5, were significantly downregulated, while those of IL11, IL1R2, and IL8 were dramatically upregulated. The DEGs were mainly enriched in the immune disease, viral protein interaction with cytokine and cytokine receptor, and toll-like receptor pathways, suggesting that hemolysin stimulation can activate the transcriptional responses. RT-qPCR experiments results of seven genes, IL-8, STAT2, CTSK, PRF1, CXCL9, TLR5, and SACS, showed that their expression was highly concordant with RNA-seq data. We clarified for the first time the key genes and signaling pathways response to hemolysin from A. hydrophila, which offers strategies for treating and preventing diseases.

Low-frequency Electrical Stimulation of the Hippocampus Plays a Role in the Treatment of Pharmacoresistant Epilepsy by Blocking the PKA-CREB Pathway.

OBJECTIVE: The objective of this study is to study the mechanism of Low frequency electrical stimulation (LFS) in the treatment of drug-resistant epilepsy by regulating the protein kinase A (PKA)-cAMP response element-binding protein (CREB) signaling pathway upstream of gamma aminobutyric acid A (GABAA) receptor. METHODS: Primary hippocampal neurons were extracted and cultured from fetal rat brains and randomly divided into the normal control group, PKA-CREB agonist group, and PKA-CREB inhibitor group. Drug-resistant epileptic rats were established and randomly divided into the pharmacoresistant group, LFS group, PKA-CREB agonist combined with hippocampal LFS group, and PKA-CREB inhibitor combined with hippocampal LFS group. The normal rats were in the normal control group and drug-sensitive rats were in the pharmacosensitive group. The seizure frequency of epileptic rats was determined using video surveillance. The expression of PKA, CREB, p-CREB, and GABAA receptor subunits α1 and ß2 of each group were detected using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting assays. RESULTS: The in vitro expression levels of PKA, CREB, and p-CREB in the agonist group were significantly higher than those in the normal control group (NRC group), while the expression levels of GABAA receptor subunits α1 and ß2 were significantly lower than those in the NRC group. The expression levels of PKA, CREB, and p-CREB in the inhibitor group were significantly lower, while the expression levels of GABAA receptor subunits α1 and ß2 were significantly higher than those in the NRC group. The in vivo seizure frequency was significantly lower in the LFS group than in the pharmacoresistant group (PRE group). Compared to the LFS group, the seizure frequency and the expression levels of PKA, CREB, and p-CREB in the rat hippocampus were significantly higher, and the expression levels of GABAA receptor subunits α1 and ß2 were significantly lower in the agonist group. The results in the inhibitor group were exactly the opposite of those in the agonist group. CONCLUSION: The PKA-CREB signaling pathway is involved in the regulation of GABAA receptor subunits α1 and ß2. In addition, LFS plays an important role in increasing GABAA receptor expression by regulating the PKA-CREB signaling pathway.

Regulatory mechanisms of GCN5 in osteogenic differentiation of MSCs in periodontitis.

OBJECTIVES: The regulatory mechanisms of GCN5 (General control non-repressed protein5) in the osteogenic differentiation of mesenchymal stem cells (MSCs) in periodontitis are still unclear. The purpose of this review focuses on the regulating roles of GCN5 in bone metabolism and periodontitis, discusses the potential molecular mechanism and provides targets and new ideas for the treatment of periodontitis. MATERIAL AND METHODS: The integrative review methodology was used. Data sources include PubMed, Cochrane Library, and additional sources. RESULTS: MSCs play an important role in the osteogenesis balance of periodontal tissue. Periodontal ligament stem cells (PDLSCs) from periodontitis patients exhibited defective osteogenic differentiation capacities. Histone acetylation is important in regulating the differentiation of different types of MSCs cells and is closely related to the reduced osteogenic differentiation of PDLSCs. GCN5, one of the first histone acetyltransferase linked to gene transcriptional activation, participates in many biological processes of mesenchymal stem cells. Downregulation of GCN5 expression and lack of GCN5 caused decreased osteogenic differentiation of PDLSCs. Intercellular information exchange may be an important way for MSCs to exert their regulatory and therapeutic functions. CONCLUSIONS: GCN5 affects the function of cell metabolism-related genes by regulating the acetylation status of histones or non-histones, thereby regulating some important progress of MSCs such as PDLSCs' osteogenic differentiation and BMCS osteogenic differentiation.

Polyetherketoneketone, a high-performance polymer for splinting mobile teeth: A clinical report.

A digital workflow for fabricating a polyetherketoneketone (PEKK) periodontal splint is described. The antibacterial properties of PEKK and the precision and efficiency of digital technology led to the provision of a splint with no adverse effects on oral hygiene or periodontal maintenance during a 2-year follow-up.