Inhibition of Extracellular Signal-Regulated Kinase Activity Improves Cognitive Function in Mice Subjected to Myocardial Infarction.

Cognitive impairment is a commonly observed complication following myocardial infarction; however, the underlying mechanisms are still not well understood. The most recent research suggests that extracellular signal-regulated kinase (ERK) plays a critical role in the development and occurrence of cognitive dysfunction-related diseases. This study aims to explore whether the ERK inhibitor U0126 targets the ERK/Signal Transducer and Activator of Transcription 1 (STAT1) pathway to ameliorate cognitive impairment after myocardial infarction. To establish a mouse model of myocardial infarction, we utilized various techniques including Echocardiography, Hematoxylin-eosin (HE) staining, Elisa, Open field test, Elevated plus maze test, and Western blot analysis to assess mouse cardiac function, cognitive function, and signal transduction pathways. For further investigation into the mechanisms of cognitive function and signal transduction, we administered the ERK inhibitor U0126 via intraperitoneal injection. Reduced total distance and activity range were observed in mice subjected to myocardial infarction during the open field test, along with decreased exploration of the open arms in the elevated plus maze test. However, U0126 treatment exhibited a significant improvement in cognitive decline, indicating a protective effect through the inhibition of the ERK/STAT1 signaling pathway. Hence, this study highlights the involvement of the ERK/STAT1 pathway in regulating cognitive dysfunction following myocardial infarction and establishes U0126 as a promising therapeutic target.

Auxin regulates bulbil initiation by mediating sucrose metabolism in Lilium lancifolium.

Lily bulbils, which serve as advantageous axillary organs for vegetative propagation, have not been extensively studied in terms of the mechanism of bulbil initiation. The functions of auxin and sucrose metabolism have been implicated in axillary organ development, but their relationship in regulating bulbil initiation remains unclear. In this study, exogenous indole-3-acetic acid (IAA) treatment increased the endogenous auxin levels at leaf axils and significantly decreased bulbil number, whereas treatment with the auxin polar transport inhibitor N-1-naphthylphthalamic acid (NPA), which resulted in a low auxin concentration at leaf axils, stimulated bulbil initiation and increased bulbil number. A low level of auxin caused by NPA spraying or silencing of auxin biosynthesis genes YUCCA FLAVIN MONOOXYGENASE-LIKE 6 (LlYUC6) and TRYPTOPHAN AMINOTRANSFERASERELATED 1 (LlTAR1) facilitated sucrose metabolism by activating the expression of SUCROSE SYNTHASES 1 (LlSusy1) and CELL WALL INVERTASE 2 (LlCWIN2), resulting in enhanced bulbil initiation. Silencing LlSusy1 or LlCWIN2 hindered bulbil initiation. Moreover, the transcription factor BASIC HELIX-LOOP-HELIX 35 (LlbHLH35) directly bound the promoter of LlSusy1, but not the promoter of LlCWIN2, and activated its transcription in response to the auxin content, bridging the gap between auxin and sucrose metabolism. In conclusion, our results reveal that an LlbHLH35-LlSusy1 module mediates auxin-regulated sucrose metabolism during bulbil initiation.

The efficacy of nasal administration of esketamine in patients having moderate-to-severe pain after preoperative CT-guided needle localization: a randomized, double-blind, placebo-controlled trial.

Background: Whether nasal administration of esketamine can provide effective analgesia is unclear in patients with acute pain after preoperative CT-guided needle localization. Methods: In this double-blind, randomized, placebo-controlled trial, patients were assigned to receive either nasal administration of esketamine (0.3 mg/kg or 0.5 mg/kg) or saline (identical in appearance to esketamine) when they had visual analog scale (VAS) pain scores >3/10 during deep breathing after preoperative CT-guided needle localization. The primary outcome was the percentage of patients with satisfactory pain relief, which was defined as VAS pain scores ≤3/10 measured 15 min after intranasal of esketamine or saline. Secondary outcomes included VAS measured following esketamine or saline, the incidence and cumulative dose of rescue hydromorphone use, and related adverse events. Results: A total of 90 patients were included in the final analysis. Following intranasal treatment, the percentage of patients with satisfactory pain relief was 16.7% (5/30) in the saline group, 56.7% (17/30) in the 0.3 mg/kg esketamine group, and 53.3% (16/30) in the 0.5 mg/kg esketamine group (p = 0.002). The median VAS during deep breathing was less after the intranasal administration of esketamine {median (IQR), 3 (3, 5) in 0.3 mg/kg or 0.5 mg/kg esketamine compared to the saline group [5 (4, 6)], p = 0.009}. The incidence of rescue hydromorphone use was detected less in the esketamine group compared to the saline group (43.3% in the 0.3 mg/kg esketamine group, 36.7% in the 0.5 mg/kg esketamine group, and 73.3% in the saline group, p = 0.010). The adverse events were similar among the three groups (p > 0.05). Conclusion: Intranasal administration of esketamine is easier and more effective in alleviating acute pain in patients after preoperative CT-guided needle localization without significant adverse effects.

Recent advances in photothermal nanomaterials-mediated detection of circulating tumor cells.

Photothermal materials have shown great potential for cancer detection and treatment due to their excellent photothermal effects. Circulating tumor cells (CTCs) are tumor cells that are shed from the primary tumor into the blood and metastasize. In contrast to other tumor markers that are free in the blood, CTCs are a collective term for all types of tumor cells present in the peripheral blood, a source of tumor metastasis, and clear evidence of tumor presence. CTCs detection enables early detection, diagnosis and treatment of tumors, and plays an important role in cancer prevention and treatment. This review summarizes the application of various photothermal materials in CTC detection, including gold, carbon, molybdenum, phosphorus, etc. and describes the significance of CTC detection for early tumor diagnosis and tumor prognosis. Focus is also put on how various photothermal materials play their roles in CTCs detection, including CT, imaging and photoacoustic and therapeutic roles. The physicochemical properties, shapes, and photothermal properties of various photothermal materials are discussed to improve the detection sensitivity and efficiency and to reduce the damage to normal cells. These photothermal materials are capable of converting radiant light energy into thermal energy for highly-sensitive CTCs detection and improving their photothermal properties by various methods, and have achieved good results in various experiments. The use of photothermal materials for CTCs detection is becoming more and more widespread and can be of significant help in early cancer screening and later treatment.

Netrin-1 Role in Nociceptive Neuron Sprouting through Activation of DCC Signaling in a Rat Model of Bone Cancer Pain.

BACKGROUND: Bone cancer pain (BCP) is a common primary or metastatic bone cancer complication. Netrin-1 plays an essential role in neurite elongation and pain sensitization. This study aimed to determine the role of netrin-1 from the metastatic bone microenvironment in BCP development and identify the associated signaling pathway for the strategy of BCP management. METHODS: The rat BCP model was established by intratibial implantation of Walker 256 cells. Von Frey filaments measured the mechanical pain threshold. Movement-induced pain was assessed using limb use scores. Expressions of associated molecules in the affected tibias or dorsal root ganglia (DRG) were measured by immunofluorescence, immunohistochemistry, real-time quantitative polymerase chain reaction, or western blotting. Transduction of deleted in colorectal cancer (DCC) signaling was inhibited by intrathecal injection of DCC-siRNA. RESULTS: In BCP rats, the presence of calcitonin gene-related peptide (CGRP)-positive nerve fibers increased in the metastatic bone lesions. The metastatic site showed enrichment of well-differentiated osteoclasts and expressions of netrin-1 and its attractive receptor DCC. Upregulation of DCC and increased phosphorylation levels of focal adhesion kinase (FAK) and Rac family small GTPase 1/Cell division cycle 42 (Rac1/Cdc42) were found in the DRG. Intrathecal administration of DCC-siRNA led to a significant reduction in FAK and Rac1/Cdc42 phosphorylation levels in the DRG, decreased nociceptive nerve innervation, and improved pain behaviors. CONCLUSIONS: Netrin-1 may contribute to the activation of the BCP by inducing nociceptive nerve innervation and improving pain behaviors.

Activation of the BMP2-SMAD1-CGRP pathway in dorsal root ganglia contributes to bone cancer pain in a rat model.

Peripheral nerve remodeling and sensitization are involved in cancer-related bone pain. As a member of the transforming growth factor-ß class, bone morphogenetic protein 2 (BMP2) is recognized to have a role in the development of the neurological and skeletal systems. Our previous work showed that BMP2 is critical for bone cancer pain (BCP) sensitization. However, the mechanism remains unknown. In the current study, we demonstrated a substantial increase in BMP2 expression in the dorsal root ganglia (DRG) in a rat model of BCP. Knockdown of BMP2 expression ameliorated BCP in rats. Furthermore, the DRG neurons of rats with BCP expressed higher levels of calcitonin gene-related peptide (CGRP), and BCP was successfully suppressed by intrathecal injection of a CGRP receptor blocker (CGRP8-37). Downregulation of BMP2 expression reduced the expression of CGRP in the DRG of rats with BCP and relieved pain behavior. Moreover, we revealed that upregulation of CGRP expression in the DRG may be induced by activation of the BMPR/Smad1 signaling pathway. These findings suggest that BMP2 contributes to BCP by upregulating CGRP in DRG neurons via activating BMPR/Smad1 signaling pathway and that therapeutic targeting of the BMP2-Smad1-CGRP pathway may ameliorate BCP in the context of advanced cancer.

Development and external validation of a novel model for predicting new clinically important atrial fibrillation after thoracoscopic anatomical lung cancer surgery: a multicenter retrospective cohort study.

BACKGROUND: New clinically important postoperative atrial fibrillation (POAF) is the most common arrhythmia after thoracoscopic anatomical lung cancer surgery and is associated with increased morbidity and mortality. The full spectrum of predictors remains unclear, and effective assessment tools are lacking. This study aimed to develop and externally validate a novel model for predicting new clinically important POAF. METHODS: This retrospective study included 14 074 consecutive patients who received thoracoscopic anatomical lung cancer surgery from January 2016 to December 2018 in Shanghai Chest Hospital. Based on the split date of 1 January 2018, we selected 8717 participants for the training cohort and 5357 participants for the testing cohort. For external validation, we pooled 2941 consecutive patients who received this surgical treatment from July 2016 to July 2021 in Shanghai Ruijin Hospital. Independent predictors were used to develop a model and internally validated using a bootstrap-resampling approach. The area under the receiver operating characteristic curves (AUROCs) and Brier score were performed to assess the model discrimination and calibration. The decision curve analysis (DCA) was used to evaluate clinical validity and net benefit. New clinically important POAF was defined as a new-onset of POAF that causes symptoms or requires treatment. RESULTS: Multivariate analysis suggested that age, hypertension, preoperative treatment, clinical tumor stage, intraoperative arrhythmia and transfusion, and operative time were independent predictors of new clinically important POAF. These seven candidate predictors were used to develop a nomogram, which showed a concordance statistic (C-statistic) value of 0.740 and good calibration (Brier score; 0.025). Internal validation revealed similarly good discrimination (C-statistic, 0.736; 95% CI: 0.705-0.768) and calibration. The decision curve analysis showed positive net benefits with the threshold risk range of 0-100%. C-statistic value and Brier score were 0.717 and 0.028 in the testing cohort, and 0.768 and 0.012 in the external validation cohort, respectively. CONCLUSIONS: This study identified seven predictors of new clinically important POAF, among which preoperative treatment, intraoperative arrhythmia, and operative time were rarely reported. The established and externally validated model has good performance and clinical usefulness, which may promote the application of prevention and treatment in high-risk patients, and reduce the development and related adverse outcomes of this event.

Dye-augmented bandgap engineering of a degradable cascade nanoreactor for tumor immune microenvironment-enhanced dynamic phototherapy of breast cancer.

Non-invasive precision tumor dynamic phototherapy has broad application prospects. Traditional semiconductor materials have low photocatalytic activity and low reactive oxygen species (ROS) production rate due to their wide band gap, resulting in unsatisfactory phototherapy efficacy for tumor treatment. Employing the dye-sensitization mechanism can significantly enhance the catalytic activity of the materials. We develop a multifunctional nanoplatform (BZP) by leveraging the benefits of bismuth-based semiconductor nanomaterials. BZP possesses robust ROS generation and remarkable near-infrared photothermal conversion capabilities for improving tumor immune microenvironment and achieving superior phototherapy sensitization. BZP produces highly cytotoxic ROS species via the photocatalytic process and cascade reaction, amplifying the photocatalytic therapy effect. Moreover, the simultaneous photothermal effect during the photocatalytic process facilitates the improvement of therapeutic efficacy. Additionally, BZP-mediated phototherapy can trigger the programmed death of tumor cells, stimulate dendritic cell maturation and T cell activation, modulate the tumor immune microenvironment, and augment the therapeutic effect. Hence, this study demonstrates a promising research paradigm for tumor immune microenvironment-improved phototherapy. STATEMENT OF SIGNIFICANCE: Through the utilization of dye sensitization and rare earth doping techniques, we have successfully developed a biodegradable bismuth-based semiconductor nanocatalyst (BZP). Upon optical excitation, the near-infrared dye incorporated within BZP promptly generates free electrons, which, under the influence of the Fermi energy level, undergo transfer to BiF3 within BZP, thereby facilitating the effective separation of electron-hole pairs and augmenting the catalytic capability for reactive oxygen species (ROS) generation. Furthermore, a cascade reaction mechanism generates highly cytotoxic ROS, which synergistically depletes intracellular glutathione, thereby intensifying oxidative stress. Ultimately, this dual activation strategy, combining oxidative and thermal damage, holds significant potential for tumor immunotherapy.

Echinacoside Prevents Sepsis-Induced Myocardial Damage via Targeting SOD2.

Echinacoside (ECH) is a prominent naturally occurring bioactive compound with effects of alleviating myocardial damage. We aimed to explore the beneficial effects of ECH against sepsis-induced myocardial damage and elucidate the potential mechanism. Echocardiography and Masson staining demonstrated that ECH alleviates cardiac function and fibrosis in the cecal ligation and puncture (CLP) model. Transcriptome profiling and network pharmacology analysis showed that there are 51 overlapping targets between sepsis-induced myocardial damage and ECH. Subsequently, chemical carcinogenesis-reactive oxygen species (ROS) were enriched in multiple targets. Wherein, SOD2 may be the potential target of ECH on sepsis-induced myocardial damage. Polymerase chain reaction results showed that ECH administration could markedly increase the expression of SOD2 and reduce the release of ROS. Combined with injecting the inhibitor of SOD2, the beneficial effect of ECH on mortality, cardiac function, and fibrosis was eliminated, and release of ROS was increased after inhibiting SOD2. ECH significantly alleviated myocardial damage in septic mice, and the therapeutic mechanism of ECH is achieved by upregulating SOD2 which decreased the release of ROS.

Topology-regulated nanocatalysts for ferroptosis-mediated cancer phototherapy.

Ferroptosis-mediated tumor treatment is constrained by the absence of single-component, activatable multifunctional inducers. Given this, a topological synthesis strategy is employed to develop an efficient bismuth-based semiconductor nano-photocatalyst (Bi2O3:S) for tumor ferroptosis therapy. Photo-excited electrons can participate in the reduction reaction to produce harmful reactive oxygen species (ROS) when exposed to near-infrared light. Meanwhile, photo-excited holes can contribute to the oxidation reaction to utilize extra glutathione (GSH) in tumors. In the acidic tumor microenvironment, bismuth ions generated from Bi2O3:S may further cooperate with GSH to amplify oxidative stress damage and achieve biodegradation. Both promote ferroptosis by downregulating glutathione peroxidase 4 (GPX4) expression. Besides, sulfur doping optimizes its near-infrared light-induced photothermal conversion efficiency, benefiting its therapeutic effect. Thus, bismuth ions and holes synergistically drive photo-activable ferroptosis in this nanoplatform, opening up new avenues for tumor therapy.

Regulating bulb dormancy release and flowering in lily through chemical modulation of intercellular communication.

Lily is a bulbous plant with an endogenous dormancy trait. Fine-tuning bulb dormancy release is still a challenge in the development of bulb storage technology. In this study, we identified three regulators of symplastic transport, 2,3-Butanedione oxime (BDM), N-Ethyl maleimide (NEM), and 2-Deoxy-D-glucose (DDG), that also regulate bulb dormancy release. We demonstrated that BDM and DDG inhibited callose synthesis between cells and promoted symplastic transport and soluble sugars in the shoot apical meristem (SAM), eventually accelerating bulb dormancy release and flowering in lilies. Conversely, NEM had the opposite effect. These three regulators can be flexibly applied to either accelerate or delay lily bulb dormancy release.

Treatment of Distal Third Humeral Shaft Fracture with Intramedullary Nail Combined with Anterior Minimally Invasive Plate Osteosynthesis.

OBJECTIVE: The treatment of distal third humeral shaft fracture is difficult. Studies have shown that anterior minimally invasive plate has lower probability of complication and higher healing rate. However there is no applicable anatomical plate at present. This study is to investigate the clinical effect of intramedullary nail combined with anterior minimally invasive plate in the treatment of distal humeral shaft fractures. METHODS: The data of 83 patients with lower humerus shaft fracture treated from September 2015 to January 2020 were analyzed. According to different treatment methods, they were divided into two groups: 40 patients were treated with intramedullary nailing combined with minimally invasive anterior plate fixation (group A), and 43 patients were treated with double plate fixation through posterior approach (group B). General preoperative data, operative time, intraoperative blood loss, total incision length, fracture healing time, shoulder and elbow visual analogue scale (VAS) score, Constant-Murley shoulder function score, Mayo elbow function score, and complications were recorded and compared between the two groups. Two independent sample t-tests was used for follow-up, age, BMI, operation time, intraoperative bleeding, total incision length, fracture healing time, Constant-Murley score and Mayo score, and rank sum test was used for VAS score of shoulder and elbow. RESULTS: There was no significant difference in preoperative general data between the two groups (p > 0.05), indicating comparability. There were no significant differences in operation time, total incision length, fracture healing time, Constant-Murley shoulder function score at the last follow-up, Mayo elbow function score, and shoulder and elbow VAS pain score between 2 groups (p > 0.05). The amount of intraoperative blood loss in observation group was 76.98 ± 16.46, which was significantly less than that in control group, and the difference was statistically significant (p < 0.01). There were no radial nerve injury, musculocutaneous nerve injury, incision infection and fracture nonunion in the observation group. In the control group, four cases of iatrogenic radial nerve injury, three cases of incision infection and three cases of fracture nonunion were found. The complication rate was 23.3% (10/43). There was statistical difference in the incidence of complications between the two groups (p < 0.01). CONCLUSION: A humeral intramedullary nail combined with an anterior minimally invasive plate in the treatment of distal humeral shaft fracture has the advantages of less soft tissue damage, less blood transfusion, high fracture healing rate and low risk of iatrogenic radial nerve injury, which is an effective method for clinical treatment of this type of fracture.

Unplanned reoperation after pulmonary surgery: Rate, risk factors and early outcomes at a single center.

Background: Unplanned reoperation is a potential risk factor for worse prognoses and reflects the quality of surgical treatment. This study compared the short-term outcomes between patients with and without reoperation and identified clinical factors predicting reoperation within 90 days following pulmonary surgery. Methods: Consecutive patients undergoing pulmonary resection from January 2012 to August 2021 at our institution were retrospectively reviewed. Clinical and operation-related data were collected and analyzed. Kaplan‒Meier, Cox hazard proportional regression, and propensity score matching were adopted for prognostic evaluation. Results: A total of 90263 patients were included: 247 (0.27%) patients required reoperation within 90 days. Patients undergoing unplanned reoperation had higher mortality and more postoperative complications than the nonreoperation group. Reoperation within 24 h was associated with reduced odds of mortality relative to reoperation beyond 24 h. Independent risk factors for unplanned reoperation were male sex, benign lung disease, specific surgical locations, lobectomy, and pneumonectomy. A history of smoking, pulmonary tuberculosis, intraoperative pleural adhesion, and postoperative complications were also identified as predisposing factors. The most common complication was hemorrhage in 75.7% (187 of 247). Conclusion: Our study found that unplanned reoperation was a rare but serious event that increased the risk of postoperative complications and mortality. We identified several risk factors that could be used to stratify patients according to their reoperation risk and suggest that high-risk patients should receive more intensive monitoring and preventive measures. Moreover, our study indicated that reoperating within 24 h could improve the outcomes for patients who needed reoperation.

GlideScope versus C-MAC D-blade videolaryngoscope for double-lumen tube intubation in patients with anticipated difficult airways: A multi-center, prospective, randomized, controlled trial.

STUDY OBJECTIVE: Videolaryngoscopes are widely used to visualize difficult airways. Our aim was to compare the GlideScope and C-MAC D-blade videolaryngoscopes for double-lumen tube (DLT) intubation in patients with difficult airways. DESIGN: A multi-center, prospective, randomized controlled trial. SETTING: Three comprehensive tertiary, high-volume hospitals from 5 December 2020 to 4 November 2021. PATIENTS: We included 348 adult patients with anticipated difficult airways who underwent elective thoracic surgery. INTERVENTIONS: Patients were randomized into two groups: GlideScope and C-MAC D-blade. Following anesthesia induction, DLT intubation was performed using different videolaryngoscopes. MEASUREMENTS: The primary outcome was the first-pass success rate of DLT intubation. All other results were recorded as secondary outcomes. MAIN RESULTS: No significant differences were observed in the first-pass success rate of DLT intubation between the GlideScope and C-MAC D-blade (86.21% and 89.66%, respectively; P = 0.323). However, compared with the GlideScope, the C-MAC D-blade provided a lower Cormack-Lehane grade (P < 0.001), lower rates of external laryngeal pressure (48 vs. 15, P < 0.001), and postprocedure sore throat (26 vs. 8, P < 0.001). The numerical rating score for difficulty of videolaryngoscope insertion into the oral cavity, delivery to the glottis, and intubation into the main bronchus were significantly lower when using the C-MAC D-blade (P < 0.001). Moreover, the duration of DLT intubation was shorter in the C-MAC D-blade group (81 s [70-97 s] vs. 95 s [78-115 s], P < 0.001). In each group, two patients underwent fiberoptic intubation after three attempts with a videolaryngoscope failed. CONCLUSIONS: In patients with difficult airways, the GlideScope and C-MAC D-blade provided a similar success rate on the first DLT intubation attempt; however, the C-MAC D-blade offers a better glottic view, easier and faster intubation, and lower incidence of sore throat.

Genome-wide analysis of the GRAS gene family in Liriodendron chinense reveals the putative function in abiotic stress and plant development.

Introduction: GRAS genes encode plant-specific transcription factors that play essential roles in plant growth and development. However, the members and the function of the GRAS gene family have not been reported in Liriodendron chinense. L. chinense, a tree species in the Magnolia family that produces excellent timber for daily life and industry. In addition, it is a good relict species for plant evolution research. Methods: Therefore, we conducted a genome-wide study of the LcGRAS gene family and identified 49 LcGRAS genes in L. chinense. Results: We found that LcGRAS could be divided into 13 sub-groups, among which there is a unique branch named HAM-t. We carried out RNA sequencing analysis of the somatic embryos from L. chinense and found that LcGRAS genes are mainly expressed after heart-stage embryo development, suggesting that LcGRAS may have a function during somatic embryogenesis. We also investigated whether GRAS genes are responsive to stress by carrying out RNA sequencing (RNA-seq) analysis, and we found that the genes in the PAT subfamily were activated upon stress treatment, suggesting that these genes may help plants survive stressful environments. We found that PIF was downregulated and COR was upregulated after the transient overexpression of PATs, suggesting that PAT may be upstream regulators of cold stress. Discussion: Collectively, LcGRAS genes are conserved and play essential roles in plant development and adaptation to abiotic stress.

Defining in vitro topical antimicrobial and antibiofilm activity of epoxy-tigliane structures against oral pathogens.

Background: Peri-implantitis has become an inexorable clinical challenge in implantology. Topical immunomodulatory epoxy-tiglianes (EBCs), derived from the Queensland blushwood tree, which induce remodeling and resolve dermal infection via induction of the inflammasome and biofilm disruption, may offer a novel therapeutic approach. Design: In vitro antimicrobial activity of EBC structures (EBC-46, EBC-1013 and EBC-147) against Streptococcus mutans, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis in minimum inhibitory concentration, growth curve and permeabilization assays were determined. Antibiofilm activity was assessed using minimum biofilm eradication concentration (MBEC) experiments. Biofilm formation and disruption assays were analyzed using confocal laser scanning microscopy, scanning electron microscopy and direct plate counting. Results: The observed antimicrobial efficacy of the tested compounds (EBC-1013 > EBC-46 > EBC-147) was directly related to significant membrane permeabilization and growth inhibition (p < 0.05) against planktonic S. mutans and P. gingivalis. Antibiofilm activity was evident in MBEC assays, with S. mutans biofilm formation assays revealing significantly lower biomass volume and increased DEAD:LIVE cell ratio observed for EBC-1013 (p < 0.05). Furthermore, biofilm disruption assays on titanium discs induced significant biofilm disruption in S. mutans and P. gingivalis (p < 0.05). Conclusions: EBC-1013 is a safe, semi-synthetic, compound, demonstrating clear antimicrobial biofilm disruption potential in peri-implantitis.

Aggressive intraoperative warming and postoperative pulmonary complications in elderly patients recovering from esophageal cancer surgery: sub-analysis of a randomized trial.

Background: Elderly patients having esophagectomies often become hypothermic which may promote complications. We tested the hypothesis that aggressive warming to a core temperature of 37°C reduces postoperative pulmonary complications (PPCs) in elderly patients having esophageal cancer resections. Methods: This study was a pre-defined sub-study of a multi-center, parallel group, superiority trial (PROTECT). Patients aged >65 years and having elective radical resection of esophageal cancer in a single center were randomly allocated into either aggressive warming group (target intraoperative core temperatures of 37°C) or routine thermal management group (target intraoperative core temperatures of 35.5°C). The primary endpoint was the incidence of PPCs. Secondary endpoints included duration of chest tube drainage and other postoperative complications. Results: A total of 300 patients were included in the primary analysis. PPCs occurred in 27 (18%) of 150 patients in the aggressive warming group and 31 (21%) of 150 patients in the routine thermal management group. The relative risk (RR) of aggressive versus routine thermal management was 0.9 (95% CI: 0.5, 1.4; p = 0.56). The duration of chest drainage in patients assigned to aggressive warming was shorter than that assigned to routine thermal management: 4 (3, 5) days vs. 5 (4, 7) days; hazard ratio (HR) 1.4 [95% CI: 1.1, 1.7]; p = 0.001. Fewer aggressively warmed patients needed chest drainage for more than 5 days: 30/150 (20%) vs. 51/150 (34%); RR:0.6 (95% CI: 0.4, 0.9; p = 0.03). The incidence of other postoperative complications were similar between the two groups. Conclusion: Aggressive warming does not reduce the incidence of PPCs in elderly patients receiving esophagectomy. The duration of chest drainage was reduced by aggressive warming. But as a secondary analysis of a planned sub-group study, these results should be considered exploratory. Clinical trial registration: https://www.chictr.org.cn/showproj.aspx?proj=37099, ChiCTR1900022257.

The inhibition mechanism of the SUR2A-containing KATP channel by a regulatory helix.

KATP channels are metabolic sensors for intracellular ATP/ADP ratios, play essential roles in many physiological processes, and are implicated in a spectrum of pathological conditions. SUR2A-containing KATP channels differ from other subtypes in their sensitivity to Mg-ADP activation. However, the underlying structural mechanism remains poorly understood. Here we present a series of cryo-EM structures of SUR2A in the presence of different combinations of Mg-nucleotides and the allosteric inhibitor repaglinide. These structures uncover regulatory helix (R helix) on the NBD1-TMD2 linker, which wedges between NBD1 and NBD2. R helix stabilizes SUR2A in the NBD-separated conformation to inhibit channel activation. The competitive binding of Mg-ADP with Mg-ATP to NBD2 mobilizes the R helix to relieve such inhibition, allowing channel activation. The structures of SUR2B in similar conditions suggest that the C-terminal 42 residues of SUR2B enhance the structural dynamics of NBD2 and facilitate the dissociation of the R helix and the binding of Mg-ADP to NBD2, promoting NBD dimerization and subsequent channel activation.

Effectiveness of pharmacological cardioversion of new-onset atrial fibrillation during thoracic surgery operations: a single-centre experience.

OBJECTIVE: Prophylactic pharmacological conversion agents could reduce the incidence of postoperative atrial fibrillation (AF) in patients undergoing thoracic operations. The current study examined whether the use of pharmacological conversion agents could help to restore sinus rhythm in patients with AF newly developed during thoracic operations. METHODS: Medical records of 18,605 patients from January 1, 2015 to December 31, 2019, at the Shanghai Chest Hospital were reviewed. Patients with non-sinus rhythm prior to the surgery (n = 128) were excluded from data analysis. The final analysis included 18,477 patients (n = 16,292 undergoing lung operations; n = 2,185 undergoing esophageal operations). RESULTS: Intraoperative AF (defined as AF lasting for at least 5 min) occurred in 646 out of a total of 18,477 subjects (3.49%). Within the 646 subjects, 258 received pharmacological conversion agents during the surgery. sinus rhythm was restored in 20.15% (52/248) of patients treated with pharmacological cardioversion and in 20.87% (81/399) patients not receiving pharmacological intervention. In a subgroup analysis of the 258 patients receiving pharmacological conversion agents, recovery of sinus rhythm was highest in beta-blocker group (35.59%, 21/59 vs. 15.78%, 15/95 in amiodarone group, p = 0.008, 5.55%, and 1/18 in amiodarone plus beta-blockers group, p = 0.016). The incidence of hypotension was higher in pharmacological conversion (27.5% vs. 9.3% in patients not receiving pharmacological intervention, p < 0.001). In subjects not recovering to sinus rhythm during the surgery (n = 513), electrical cardioversion in post-anesthesia care unit (PACU) restored sinus rhythm in > 98% of the cases (155/158 vs. 63/355 in subjects not receiving cardioversion; p < 0.001). CONCLUSIONS: Our experience shows that pharmacological conversion, in general, failed to show better treatment effectiveness on intraoperative new-onset AF within period of surgery except for beta-blockers. Patients with AF persisting beyond the surgery could be effectively managed with electrical cardioversion.

Research progress of advanced microneedle drug delivery system and its application in biomedicine.

Transdermal drug delivery is an effective way of drug delivery in addition to oral and intravenous administration. Among them, microneedle administration is a new type of subcutaneous drug delivery, which forms micron-level pores on the surface of the skin, making the drug enter the dermis through the cuticular layer of the skin in the least invasive way. This mode of drug delivery not only increases the permeation efficiency of transdermal drug delivery but also improves the bioavailability of drug delivery. At present, there are many kinds of research on microneedles, such as solid microneedles, hollow microneedles, soluble polymer microneedles, etc. However, some new microneedle drug delivery systems have been gradually developed and applied with the development of microneedle drug delivery technology, for meeting the more complex pathological environment. In this review, we focus on the principle, structure, and function of some new types of microneedles, such as stimulus-response microneedles, iontophoresis microneedles, and bionic microneedles. We summarize the effects of materials, geometry, and size on the properties of microneedles as well as their applications and potential developments in the field of biomedicine. We hope that this review can provide new ideas and help with the development of new microneedle drug delivery systems.