Evaluation of hemostatic, anti-inflammatory, wound healing, skin irritation and allergy, and antimicrobial properties of active fraction from the ethanol extract of Chromolaena odorata (L.) R.M. King & H. Rob.

ETHNOPHARMACOLOGICAL RELEVANCE: Chromolaenaodorata (L.) R.M. King & H. Rob, a perennial herb, has been traditionally utilized as a herbal remedy for treating leech bites, soft tissue wounds, burn wounds, skin infections, and dento-alveolitis in tropical and subtropical regions. AIM OF THE STUDY: The present study was to analyze the active fraction of C. odorata ethanol extract and investigate its hemostatic, anti-inflammatory, wound healing, and antimicrobial properties. Additionally, the safety of the active fraction as an external preparation was assessed through skin irritation and allergy tests. MATERIALS AND METHODS: The leaves and stems of C. odorata were initially extracted with ethanol, followed by purification through AB-8 macroporous adsorption resin column chromatography to yield different fractions. These fractions were then screened for hemostatic activity in mice and rabbits to identify the active fraction. Subsequently, the hemostatic effect of the active fraction was assessed through the bleeding time of the rabbit ear artery in vivo and the coagulant time of rabbit blood in vitro. The anti-inflammatory activity of the active fraction was tested on mice ear edema induced by xylene and rat paw edema induced by carrageenin. Furthermore, the active fraction's promotion effect on wound healing was evaluated using a rat skin injury model, and skin safety tests were conducted on rabbits and guinea pigs. Lastly, antimicrobial activities against two Gram-positive bacteria (G+, Staphylococcus aureus and S. epidermidis) and three Gram-negative bacteria (G-, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) were determined using the plate dilution method. RESULTS: The ethanol extract of C. odorata leaves and stems was fractionated into 30%, 60%, and 90% ethanol eluate fractions. These fractions demonstrated hemostatic activity, with the 30% ethanol eluate fraction (30% EEF) showing the strongest effect, significantly reducing bleeding time (P < 0.05). A concentration of 1.0 g/mL of the 30% EEF accelerated cutaneous wound healing in rats on the 3rd, 6th, and 9th day post-operation, with the healing effect increasing over time. No irritation or allergy reactions were observed in rabbits and guinea pigs exposed to the 30% EEF. Additionally, the 30% EEF exhibited mild inhibitory effect on mice ear and rat paw edema, as well as antimicrobial activity against tested bacteria, with varying minimal inhibitory concentration (MIC) values. CONCLUSIONS: The 30% EEF demonstrated a clear hemostatic effect on rabbit bleeding time, a slight inhibitory effect on mice ear edema and rat paw edema, significant wound healing activity in rats, and no observed irritation or allergic reactions. Antibacterial activity was observed against certain clinically isolated bacteria, particularly the G- bacteria. This study lays the groundwork for the potential development and application of C. odorata in wound treatment.

GPC3-targeted CAR-T cells expressing GLUT1 or AGK exhibit enhanced antitumor activity against hepatocellular carcinoma.

Chimeric antigen receptor-expressing T (CAR-T) cells induce robust antitumor responses in patients with hematologic malignancies. However, CAR-T cells exhibit only limited efficacy against solid tumors such as hepatocellular carcinoma (HCC), partially due to their limited expansion and persistence. CD8+ T cells, as key components of the adaptive immune response, play a central role in antitumor immunity. Aerobic glycolysis is the main metabolic feature of activated CD8+ T cells. In the tumor microenvironment, however, the uptake of large amounts of glucose by tumor cells and other immunosuppressive cells can impair the activation of T cells. Only when tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment have a glycolytic advantage might the effector function of T cells be activated. Glucose transporter type 1 (GLUT1) and acylglycerol kinase (AGK) can boost glycolytic metabolism and activate the effector function of CD8+ T cells, respectively. In this study, we generated GPC3-targeted CAR-T cells overexpressing GLUT1 or AGK for the treatment of HCC. GPC3-targeted CAR-T cells overexpressing GLUT1 or AGK specifically and effectively lysed GPC3-positive tumor cells in vitro in an antigen-dependent manner. Furthermore, GLUT1 or AGK overexpression protected CAR-T cells from apoptosis during repeated exposures to tumor cells. Compared with second-generation CAR-T cells, GPC3-targeted CAR-T cells overexpressing GLUT1 or AGK exhibited greater CD8+ T-cell persistence in vivo and better antitumor effects in HCC allograft mouse models. Finally, we revealed that GLUT1 or AGK maintained anti-apoptosis ability in CD8+ T cells via activation of the PI3K/Akt pathway. This finding might identify a therapeutic strategy for advanced HCC.

Highly-dispersed 2D NiFeP/CoP heterojunction trifunctional catalyst for efficient electrolysis of water and urea.

The electrocatalytic production of "green hydrogen", such as through the electrolysis of water or urea has been vigorously advocated to alleviate the energy crisis. However, their electrode reactions including oxygen evolution reaction (OER), urea oxidation reaction (UOR), and hydrogen evolution reaction (HER) all suffer from sluggish kinetics, which urgently need catalysts to accelerate the processes. Herein, we design and prepare an OER/UOR/HER trifunctional catalyst by transforming the homemade CoO nanorod into a two-dimensional (2D) ultrathin heterojunction nickel-iron-cobalt hybrid phosphides nanosheet (NiFeP/CoP) via a hydrothermal-phosphorization method. Consequently, a strong electronic interaction was found among the Ni2P/FeP4/CoP heterogeneous interfaces, which regulates the electronic structure. Besides the high mass transfer property of 2D nanosheet, Ni2P/FeP4/CoP displays improved OER/UOR/HER performance. At 10 mA cm-2, the OER overpotential reaches 274 mV in 1.0 M KOH, and the potential of UOR is only 1.389 V in 1.0 M KOH and 0.33 M urea. More strikingly, the two-electrode systems for electrolysis water and urea-assisted electrolysis water assembled by NiFeP/CoP could maintain long-term stability for 35 h and 12 h, respectively. This work may help to pave the way for upcoming research horizons of multifunctional electrocatalysts.

Refrigerated storage stimulates isoflavone and γ-aminobutyric acid accumulation in germinated soybeans.

This study aims to investigate the quality changes of germinated soybeans during refrigerated storage (4 °C), with an emphasis on the stimulatory effect of refrigeration on their special functional compounds. After germinating for two days, germinated soybeans were stored at 4 °C for seven days, while the germinated soybeans stored at 25 °C served as control group. The results showed that refrigerated storage significantly affected the physiological changes in germinated soybeans. The weight loss rate, browning rate, malondialdehyde (MDA) content and H2O2 content all decreased dramatically during refrigerated storage compared to the control group. The total phenolic and total flavonoid contents of germinated soybeans under refrigeration exhibited a trend of increasing and then decreasing over time. Additionally, during refrigerated storage, the total isoflavone content reached a peak of 8.72 g/kg on the fifth day, in which the content of daidzein and glycitin increased by 45% and 49% respectively, when compared with the control group. Moreover, the content of γ-aminobutyric acid (GABA) peaked on the first day, and kept a high level during storage. In which, the refrigerated group was 2.35-, 2.88-, 1.67-fold respectively after storage for three to seven days. These results indicated that refrigeration stimulated the biosynthesis of isoflavones and GABA in germinated soybeans during storage. More importantly, there was a sequential difference in the timing of the stimulation of the two functional components under refrigeration.

A cost-effectiveness analysis of fluoride varnish application in preventing Root caries in elderly persons: a Markov simulation study.

BACKGROUND: Root caries are prevalent issues that affect dental health, particularly among elderly individuals with exposed root surfaces. Fluoride therapy has shown effectiveness in preventing root caries, but limited studies have addressed its cost-effectiveness in elderly persons population. This study aimed to evaluate the cost-effectiveness of a fluoride treatment program for preventing root caries in elderly persons within the context of Chinese public healthcare. METHODS: A Markov simulation model was adopted for the cost-effectiveness analysis in a hypothetical scenario from a healthcare system perspective. A 60-year-old subject with 23 teeth was simulated for 20 years. A 5% sodium fluoride varnish treatment was compared with no preventive intervention in terms of effectiveness and cost. Tooth years free of root caries were set as the effect. Transition probabilities were estimated from the data of a community-based cohort and published studies, and costs were based on documents published by the government. The incremental cost-effectiveness ratio (ICER) was calculated to evaluate cost-effectiveness. Univariate and probabilistic sensitivity analyses were performed to evaluate the influence of data uncertainty. RESULTS: Fluoride treatment was more effective (with a difference of 10.20 root caries-free tooth years) but also more costly (with a difference of ¥1636.22). The ICER was ¥160.35 per root caries-free tooth year gained. One-way sensitivity analysis showed that the risk ratio of root caries in the fluoride treatment group influenced the result most. In the probabilistic sensitivity analysis, fluoride treatment was cost-effective in 70.5% of the simulated cases. CONCLUSIONS: Regular 5% sodium fluoride varnish application was cost-effective for preventing root caries in the elderly persons in most scenarios with the consideration of data uncertainty, but to a limited extent. Improved public dental health awareness may reduce the incremental cost and make the intervention more cost-effective. Overall, the study shed light on the economic viability and impact of such preventive interventions, providing a scientific basis for dental care policies and healthcare resource allocation.

Harnessing Mechanical Stress with Viscoelastic Biomaterials for Periodontal Ligament Regeneration.

The viscoelasticity of mechanically sensitive tissues such as periodontal ligaments (PDLs) is key in maintaining mechanical homeostasis. Unfortunately, PDLs easily lose viscoelasticity (e.g., stress relaxation) during periodontitis or dental trauma, which disrupt cell-extracellular matrix (ECM) interactions and accelerates tissue damage. Here, Pluronic F127 diacrylate (F127DA) hydrogels with PDL-matched stress relaxation rates and high elastic moduli are developed. The hydrogel viscoelasticity is modulated without chemical cross-linking by controlling precursor concentrations. Under cytomechanical loading, F127DA hydrogels with fast relaxation rates significantly improved the fibrogenic differentiation potential of PDL stem cells (PDLSCs), while cells cultured on F127DA hydrogels with various stress relaxation rates exhibited similar fibrogenic differentiation potentials with limited cell spreading and traction forces under static conditions. Mechanically, faster-relaxing F127DA hydrogels leveraged cytomechanical loading to activate PDLSC mechanotransduction by upregulating integrin-focal adhesion kinase pathway and thus cytoskeletal rearrangement, reinforcing cell-ECM interactions. In vivo experiments confirm that faster-relaxing F127DA hydrogels significantly promoted PDL repair and reduced abnormal healing (e.g., root resorption and ankyloses) in delayed replantation of avulsed teeth. This study firstly investigated how matrix nonlinear viscoelasticity influences the fibrogenesis of PDLSCs under mechanical stimuli, and it reveals the underlying mechanobiology, which suggests novel strategies for PDL regeneration.

Lactic acid bacteria modulate the gastrointestinal digestive behavior of soy glycinin and correlation with its immunoreactivity: a peptidomic study.

Lactic acid bacterial fermentation helps reduce the immunoreactivity of soy protein. Nevertheless, the effect of lactic acid bacterial fermentation on a particular soy allergen and the consequent dynamic change of epitopes during gastrointestinal digestion are unclear. In this study, soy glycinin was isolated and an in vitro dynamic gastrointestinal model was established to investigate the dynamic change in the immunoreactivity and peptide profile of unfermented (UG) and fermented glycinin (FG) digestates. The results demonstrated that the FG intestinal digestate had a lower antigenicity (0.08%-0.12%) and IgE-binding capacity (1.49%-3.61%) towards glycinin at the early (I-5) and middle (I-30) stages of gastrointestinal digestion, especially those prepared at 2% (w/v) protein concentration. Peptidomic analysis showed that the glycinin subunits G1 and G2 were the preferred ones to release the most abundant peptides, whereas G2, G4, and G5 had an elevated epitope-cleavage rate in FG at stages I-5 and I-30. Three-dimensional modeling revealed that fermentation-induced differential degradation epitopes in gastrointestinal digestion were predominantly located in the α-helix and ß-sheet structures. They were closely correlated with the reduced immunoreactivity of soy glycinin.

A comparative analysis of laryngeal nerve damage in patients with idiopathic vocal cord paralysis exhibiting different paralytic sides.

Objective: To assess the extent of recurrent laryngeal nerve (RLN) and superior laryngeal nerve (SLN) damage in patients with idiopathic vocal cord paralysis (IVCP) exhibiting different paralytic sides. Methods: A total of 84 IVCP cases were evaluated using stroboscopic laryngoscopy, voice analysis, and laryngeal electromyography (LEMG). The results were compared between patients with left-sided paralysis and right-sided paralysis based on different disease courses (less than or more than 3 months). Results: Initially, the average age and disease progression of IVCP patients were found to be similar regardless of the side of paralysis (p > .05). Additionally, there were no significant variations in voice indicators, such as MPT, DSI, and VHI, between IVCP patients with left and right vocal cord paralysis (p > .05). Furthermore, no disparities were detected in the latencies and amplitudes of the paralyzed RLN and SLN, as well as the durations and amplitudes of the action potentials in the paralyzed TM and PCM, among IVCP patients with left and right vocal cord paralysis (p > .05). Notably, the amplitudes of the left paralytic CM were significantly lower than those of the right paralytic CM (0.45 vs. 0.53, Z = -2.013, p = .044). In addition, no disparities were observed in APDs and amplitudes between the ipsilateral PCM and TM, either for patients with left or right vocal fold paralysis (p > .05). Finally, all the IVCP patients were subdivided into two subgroups according to different disease course (less than or more than 3 months), and in each subgroup, the comparison of voice indicators and LEMG results in IVCP patients with left or right vocal fold paralysis were similar with the above findings (p > .05). Conclusion: Overall, the degree of RLN and SLN damage appeared to be similar in IVCP patients with left and right vocal cord paralysis, provided that the disease course was comparable. Level of Evidence: 4.

Global fungal-host interactome mapping identifies host targets of candidalysin.

Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection.

The effectiveness of various treatment approaches for laryngeal contact granulomas.

OBJECTIVES: To assess and compare the effectiveness of various treatment approaches for laryngeal contact granulomas (LCG). METHODS: A retrospective analysis was conducted on a cohort of 45 patients diagnosed with LCG at the Second Affiliated Hospital of Xi'an Jiaotong University from October 2017 to May 2023. Based on the treatment modalities administered, patients were categorized into three groups: acid suppression alone, hormone injection combined with acid suppression, and surgery combined with acid suppression. Subsequently, the study compared differences in treatment efficacy and average healing time among these three groups, using various indicators. RESULTS: The findings indicate that the granuloma size in LCG patients with hoarseness (0.126, 95% CI 0.087-0.288) was significantly greater compared to LCG patients without hoarseness (0.047, 95% CI 0.014-0.083) (P = 0.001). However, there were no significant variations in age, morphology (unlobulated/lobulated), laterality ratio (left/right), sex ratio (male/female), history of tracheal intubation (non-intubation/intubation), and RFS score (RFS > 7/RFS ≤ 7) (P > 0.05), regardless of the presence of hoarseness symptoms. At the treatment observation endpoint of 3 months, the curative ratio in the group receiving hormone injection combined with acid suppression was found to be significantly higher compared to the group receiving acid suppression alone (P = 0.018). In addition, the average healing time of patients in the hormone injection combined with acid suppression group was notably shorter than that of the acid suppression alone group (P = 0.007). CONCLUSIONS: The combination of hormonal injections and acid suppression may enhance the curative ratio and expedite the healing time of LCG.

Digestive characteristics of extracellular polysaccharide from Lactiplantibacillus plantarum T1 and its regulation of intestinal microbiota.

This study assessed the potential prebiotic characteristics of the previously reported Lactiplantibacillus plantarum extracellular polysaccharide (EPS-T1) with immunological activity. EPS-T1 was a novel heteropolysaccharide composed of glucose and galactose (1.00:1.21), with a molecular weight of 1.41 × 106 Da. The monosaccharide composition, molecular weight, fourier transform infrared, and 1H NMR analysis showed that EPS-T1 was well tolerated in the simulated oral cavity, gastric fluid, and small intestinal fluid environments, and was not easily degraded. Meanwhile, EPS-T1 could effectively be used as a carbon source to promote the growth of beneficial Lactobacillus species (Lactobacillus delbrueckii ssp. Bulgaricus, Streptococcus thermophilus, Lacticaseibacillus rhamnose GG, Lactiplantibacillus plantarum, Lacticaseibacillus paracasei and Lactobacillus reuteri). After 24 h of fecal fermentation, EPS-T1(5 mg/mL) effectively reduced the relative abundance of harmful bacteria such as the Escherichia-Shigella, Citrobacter, Fusobacterium, Parasutterella, and Lachnoclostridium. While, the level content of beneficial flora (Bacteroides, Blautia, Phascolarctobacterium, Bifidobacterium, Parabacteroides, and Subdoligranulum) were significantly increased. In addition, EPS-T1 was able to significantly promote the enrichment of short-chain fatty acids such as acetic acid, propionic acid and butyric acid. These results provide some basis for the functional application of EPS-T1 as a potential prebiotic.

Construction of hypoallergenic microgel by soy major allergen ß-conglycinin through enzymatic hydrolysis and lactic acid bacteria fermentation.

Soy allergenicity is a public concern, and the combination of multiple processing methods may be a promising strategy for reducing soy allergenicity. In this study, a novel two-step enzymatic hydrolysis followed by lactic acid bacteria fermentation was proposed for the construction of hypoallergenic soybean protein microgel. ß-Conglycinin was used as the main soy allergen. The effects of different enzymatic hydrolysis (Alcalase, Neutrase, and Protamex) and LAB fermentation on ß-conglycinin microgel formation and its immunoreactivity were investigated. Results showed that the use of different enzymes and the attainment of different degrees of hydrolysis affected the particle distribution and zeta potential in the microgels and leads to differences in microstructure and immunoreactivity. All hydrolysates compared with intact protein accelerated the formation of gel during LAB fermentation. Among the three assayed enzymes, fermented Protamex hydrolysates at 60 min (PF-60) demonstrated a microgel with an overall reduced average particle size (741.20±7.18 nm), lower absolute values of zeta potential (10.43±0.65 mV), and regular gel network. The antigenicity and IgE-binding capacity decreased to the lowest value of 0.30 % and 6.93 %, respectively. Peptidomics and immunoinformatic analysis suggested that PF-60 disrupted 17/30, 16/44, and 23/75 epitopes in the α, α', and ß subunits, respectively. Unlike the LAB-fermented unhydrolyzed ß-conglycinin disrupted epitopes mostly located at the loop domain, PF-60 primarily promoted the exposure and disruption of allergen epitopes with ß-sheet structure located at the core barrel domain. These findings can provide new perspectives on the preparation of hypoallergenic soybean-gel products on edible particulate systems.

Effects of Lacticaseibacillus paracasei SNB-derived postbiotic components on intestinal barrier dysfunction and composition of gut microbiota.

The bacterial surface components are considered as effector molecules and show the potential to support intestinal health, but the detailed mechanism of how the gut microbiota changes after the intervention of surface molecules is still unknown. In the present study, capsular polysaccharide (B-CPS) and surface layer protein (B-SLP) were extracted from Lacticaseibacillus paracasei S-NB. The protective effect of direct administration of B-CPS (100 µg/mL) and B-SLP (100 µg/mL) on intestinal epithelial barrier dysfunction was verified based on the LPS-induced Caco-2 cell model. Additionally, the B-CPS and B-SLP could be utilized as carbon source and nitrogen source for the growth of several Lactobacillus strains, respectively. The postbiotic potential of B-CPS and B-SLP was further evaluated by in vitro fermentation with fecal cultures. The B-CPS and a combination of B-CPS and B-SLP regulated the composition of gut microbiota by increasing the relative abundances of Bacteroides, Bifidobacterium, Phascolarctobacterium, Parabacteroides, Subdoligranulum and Collinsella and decreasing the abundance of pathogenic bacteria like Escherichia-Shigella, Blautia, Citrobacter and Fusobacterium. Meanwhile, the total short-chain fatty acid production markedly increased after fermentation with either B-CPS individually or in combination with B-SLP. These results provided an important basis for the application of B-CPS and B-SLP as postbiotics to improve human intestinal health.

Recovery of Volitional Motor Control and Overground Walking in Participants With Chronic Clinically Motor Complete Spinal Cord Injury: Restoration of Rehabilitative Function With Epidural Spinal Stimulation (RESTORES) Trial-A Preliminary Study.

Spinal cord injury (SCI) is damage to any part of the spinal cord resulting in paralysis, bowel and/or bladder incontinence, and loss of sensation and other bodily functions. Current treatments for chronic SCI are focused on managing symptoms and preventing further damage to the spinal cord with limited neuro-restorative interventions. Recent research and independent clinical trials of spinal cord stimulation (SCS) or intensive neuro-rehabilitation including neuro-robotics in participants with SCI have suggested potential malleability of the neuronal networks for neurological recovery. We hypothesize that epidural electrical stimulation (EES) delivered via SCS in conjunction with mental imagery practice and robotic neuro-rehabilitation can synergistically improve volitional motor function below the level of injury in participants with chronic clinically motor-complete SCI. In our pilot clinical RESTORES trial (RESToration Of Rehabilitative function with Epidural spinal Stimulation), we investigate the feasibility of this combined multi-modal approach in restoring volitional motor control and achieving independent overground locomotion in participants with chronic motor complete thoracic SCI. Secondary aims are to assess the safety of this combination therapy including the off-label SCS usage as well as improving functional outcome measures. To our knowledge, this is the first clinical trial that investigates the combined impact of this multi-modal EES and rehabilitation strategy in participants with chronic motor complete SCI. Two participants with chronic motor-complete thoracic SCI were recruited for this pilot trial. Both participants have successfully regained volitional motor control below their level of SCI injury and achieved independent overground walking within a month of post-operative stimulation and rehabilitation. There were no adverse events noted in our trial and there was an improvement in post-operative truncal stability score. Results from this pilot study demonstrates the feasibility of combining EES, mental imagery practice and robotic rehabilitation in improving volitional motor control below level of SCI injury and restoring independent overground walking for participants with chronic motor-complete SCI. Our team believes that this provides very exciting promise in a field currently devoid of disease-modifying therapies.

Traumatic cavernous sinus syndrome - A peculiar presentation of multiple cranial nerve neuropathies following a minor head injury: Case report and literature review.

BACKGROUND: In patients with traumatic head injuries, the percentage of cranial nerve injuries (CNI) range from4.3 to 17.6% in which majority are isolated CNI[1-5].In present literature, moderate to severe types of head injuries are often studied which may result in a lack of representation and description of CNI associated with minor head injuries (MHI). Alongside this peculiar case of a traumatic cavernous sinus syndrome (CSS) that is non-thrombotic and non-fistulous in nature, this paper aims to analyse traumatic CNI in non-severe head injuries and the surrounding literature. CASE REPORT: A 65-year-old man who had sustained a minor head injury was found to have CNI of III, IV and VI.Brain imaging showed scattered traumatic subarachnoid haemorrhage and a non-displaced right zygomatic arch fracture. Despite the short course of high dose dexamethasone, he showed only partial recovery of his CNI after one year. CONCLUSION: We present a case of traumatic CSS likely secondary to tractional injury from a MHI. Injury to the extraocular nerves wasfound to be one of the more commonly observed combination of CNI from the literature review conducted. In patients with MHI, multiple CNI is less common. Hence, consideration should be given to work upfor secondary causes such as tumours. There is presently no known clear identifiable pattern of CNI associated with MHI. CT brain findings of skull base fractures and early onset of cranial nerve palsies are generally associated with worse outcomes. More remains to be studied about tractional CNI in non-severe head injuries.

Knowledge, attitude, and practice of patients living with inflammatory bowel disease: A cross-sectional study.

BACKGROUND: Patients with inflammatory bowel diseases (IBDs) generally have poor knowledge, attitude, and practice of their disease, while the data from China are lacking. AIM: To address this knowledge disparity among Chinese patients with IBD. METHODS: This web-based, cross-sectional study was conducted on a cohort of IBD patients who visited the Second Affiliated Hospital of Wenzhou Medical University between December 2022 and February 2023. Their socio-demographic information and the knowledge, attitude, and practice scores were collected and estimated using a self-designed questionnaire. Pearson's correlation analysis was used to determine the pairwise correlations among knowledge, attitude, and practice scores. A multivariate logistic regression analysis was further performed to determine the independent factors associated with their knowledge, attitude, and practice scores. RESULTS: A total of 353 patients (224 males) with IBD completed the questionnaires. The mean knowledge, attitude, and practice scores were 10.05 ± 3.46 (possible range: 0-14), 41.58 ± 5.23 (possible range: 0-56), 44.20 ± 7.39 (possible range: 0-56), respectively, indicating good knowledge, positive attitude, and proactive practice toward IBD. Pearson's correlation analysis showed that the knowledge score had significant positive correlations with the attitude score (r = 0.371, P < 0.001) and practice score (r = 0.100, P < 0.001). The attitude score had a significant positive correlation with the practice score (r = 0.452, P < 0.001). Moreover, multivariate logistic regression analysis showed that aged 30-40 years [odds ratio (OR) = 4.06, 95% confidence interval (CI): 1.04-15.82, P = 0.043], middle school education (OR = 3.98, 95%CI: 1.29-12.33, P = 0.017), high school/technical secondary school education (OR = 14.06, 95%CI: 3.92-50.38, P < 0.001), and junior college/bachelor's degree and above education (OR = 15.20, 95%CI: 4.15-55.650, P < 0.001) were independently associated with good knowledge. The higher knowledge score was independently associated with a positive attitude (OR = 1.23, 95%CI: 1.11-1.36, P < 0.001). The higher attitude score was independently associated with proactive practice (OR = 1.20, 95%CI: 1.11-1.30, P < 0.001). CONCLUSION: Chinese patients with IBD might have good knowledge, a positive attitude, and proactive practice toward their disease. However, a small number of specific items require education.

High power, broad tuning quantum cascade laser at λ ∼ 8.9 µm.

Many molecules have broad fingerprint absorption spectra in mid-wave infrared range which requires broadly tunable lasers to cover the interested spectrum in one scan. We report a strain-balanced, InAlAs/InGaAs/InP quantum cascade laser structure based on diagonal transition active region with high output power and and wide tuning range at λ ∼ 8.9 µm. The maximum pulsed optical power and the wall-plug efficiency at room temperature are 4 W and 11.7%, respectively. Maximum continuous wave double-facet power is 1.2 W at 25 °C for a 4 mm by 9 µm laser mounted epi-side down on a diamond/copper composite submount. The maximum pulsed and continuous wave external-cavity tuning range are from 7.71 µm to 9.15 µm and from 8 µm to 8.9 µm, respectively. The continuous wave power of the external cavity mode exceeds 200 mW across the entire spectrum.

GDF15 is a major determinant of ketogenic diet-induced weight loss.

A ketogenic diet (KD) has been promoted as an obesity management diet, yet its underlying mechanism remains elusive. Here we show that KD reduces energy intake and body weight in humans, pigs, and mice, accompanied by elevated circulating growth differentiation factor 15 (GDF15). In GDF15- or its receptor GFRAL-deficient mice, these effects of KD disappeared, demonstrating an essential role of GDF15-GFRAL signaling in KD-mediated weight loss. Gdf15 mRNA level increases in hepatocytes upon KD feeding, and knockdown of Gdf15 by AAV8 abrogated the obesity management effect of KD in mice, corroborating a hepatic origin of GDF15 production. We show that KD activates hepatic PPARγ, which directly binds to the regulatory region of Gdf15, increasing its transcription and production. Hepatic Pparγ-knockout mice show low levels of plasma GDF15 and significantly diminished obesity management effects of KD, which could be restored by either hepatic Gdf15 overexpression or recombinant GDF15 administration. Collectively, our study reveals a previously unexplored GDF15-dependent mechanism underlying KD-mediated obesity management.

Discovery of Pyrazolo[1,5-a]pyrimidine Derivative as a Novel and Selective ALKBH5 Inhibitor for the Treatment of AML.

M6A (N6-methyladenosine) plays a significant role in regulating RNA processing, splicing, nucleation, translation, and stability. AlkB homologue 5 (ALKBH5) is an Fe(II)/2-oxoglutarate (2-OG)-dependent dioxygenase that demethylates mono- or dimethylated adenosines. ALKBH5 can be regarded as an oncogenic factor for various human cancers. However, the discovery of potent and selective ALKBH5 inhibitors remains a challenge. We identified DDO-2728 as a novel and selective inhibitor of ALKBH5 by structure-based virtual screening and optimization. DDO-2728 was not a 2-oxoglutarate analogue and could selectively inhibit the demethylase activity of ALKBH5 over FTO. DDO-2728 increased the abundance of m6A modifications in AML cells, reduced the mRNA stability of TACC3, and inhibited cell cycle progression. Furthermore, DDO-2728 significantly suppressed tumor growth in the MV4-11 xenograft mouse model and showed a favorable safety profile. Collectively, our results highlight the development of a selective probe for ALKBH5 that will pave the way for the further study of ALKBH5 targeting therapies.