Phosphorylation of GntR reduces Streptococcus suis oxidative stress resistance and virulence by inhibiting NADH oxidase transcription.

GntR transcription factor of Streptococcus suis serotype 2 (SS2) is a potential substrate protein of STK, but the regulation mechanisms of GntR phosphorylation are still unclear. This study confirmed that STK phosphorylated GntR in vivo, and in vitro phosphorylation experiments showed that STK phosphorylated GntR at Ser-41. The phosphomimetic strain (GntR-S41E) had significantly reduced lethality in mice and reduced bacterial load in the blood, lung, liver, spleen, and brain of infected mice compared to wild-type (WT) SS2. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) experiments demonstrated that the promoter of nox was bound by GntR. The phosphomimetic protein GntR-S41E cannot bind to the promoter of nox, and the nox transcription levels were significantly reduced in the GntR-S41E mutant compared to WT SS2. The virulence in mice and the ability to resist oxidative stress of the GntR-S41E strain were restored by complementing transcript levels of nox. NOX is an NADH oxidase that catalyzes the oxidation of NADH to NAD+ with the reduction of oxygen to water. We found that NADH is likely accumulated under oxidative stress in the GntR-S41E strain, and higher NADH levels resulted in increased amplified ROS killing. In total, we report GntR phosphorylation could inhibit the transcription of nox, which impaired the ability of SS2 to resist oxidative stress and virulence.

Glaesserella parasuis serotype 5 breaches the porcine respiratory epithelial barrier by inducing autophagy and blocking the cell membrane Claudin-1 replenishment.

Glaesserella parasuis (G. parasuis), the primary pathogen of Glässer's disease, colonizes the upper respiratory tract and can break through the epithelial barrier of the respiratory tract, leading to lung infection. However, the underlying mechanisms for this adverse effect remain unclear. The G. parasuis serotype 5 SQ strain (HPS5-SQ) infection decreased the integrity of piglets' lung Occludin and Claudin-1. Autophagy regulates the function of the epithelial barrier and tight junction proteins (TJs) expression. We tested the hypothesis that HPS5-SQ breaking through the porcine respiratory epithelial barrier was linked to autophagy and Claudin-1 degradation. When HPS5-SQ infected swine tracheal epithelial cells (STEC), autophagosomes encapsulated, and autolysosomes degraded oxidatively stressed mitochondria covered with Claudin-1. Furthermore, we found that autophagosomes encapsulating mitochondria resulted in cell membrane Claudin-1 being unable to be replenished after degradation and damaged the respiratory tract epithelial barrier. In conclusion, G. parasuis serotype 5 breaks through the porcine respiratory epithelial barrier by inducing autophagy and interrupting cell membrane Claudin-1 replenishment, clarifying the mechanism of the G. parasuis infection and providing a new potential target for drug design and vaccine development.

Fluorescence and colorimetric dual-mode multienzyme cascade nanoplatform based on CuNCs/FeMn-ZIF-8/PCN for detection of sarcosine.

It is critical to develop a highly efficient and sensitive method for detecting the biomarker sarcosine (SA) of prostate cancer due to its importance for men's health. In our work, a fluorescence (FL) and colorimetric dual-mode multienzyme cascade nanoplatform for SA detection was designed and constructed. CuNCs/FeMn-ZIF-8/PCN nanocomposites with high FL properties and peroxidase-like activity were successfully prepared by encapsulating copper nanoclusters (CuNCs) into FeMn-ZIF-8 and then loaded onto P-doped graphitic carbon nitride (PCN). Furthermore, the nanocomposites served as carriers for the immobilization of sarcosine oxidase (SOX) to construct a high-efficiency dual-mode multienzyme cascade nanoplatform CuNCs/SOX@FeMn-ZIF-8/PCN for the detection of SA. The intermediate H2O2 generated in the cascade caused the FL quenching of nanocomposites and the discoloration of 3,3',5,5'-tetramethylbenzidin. The linear ranges for SA detection in the dual-mode system were 1-100 µM (FL) and 1-200 µM (colorimetric), with detection limits of 0.34 and 0.59 µM, respectively. This nanoplatform exhibited notable repeatability, specificity, and stability, making it suitable for detecting sarcosine in real human urine samples. Therefore, this dual-mode multienzyme cascade nanoplatform would have a potential applicative prospect for detecting SA and other biomarkers in real clinical samples.

Building Uniformly Structured Polymer Memristors via a 2D Conjugation Strategy for Neuromorphic Computing.

Polymer memristors represent a highly promising avenue for the advancement of next-generation computing systems. However, the intrinsic structural heterogeneity characteristic of most polymers often results in organic polymer memristors displaying erratic resistive switching phenomena, which in turn lead to diminished production yields and compromised reliability. In this study, a 2D conjugated polymer, named PBDTT-BPQTPA, is synthesized by integrating the coplanar bis(thiophene)-4,8-dihydrobenzo[1,2-b:4,5-b]dithiophene (BDTT) as an electron-donating unit with a quinoxaline derivative serving as an electron-accepting unit. The incorporation of triphenylamine groups at the quinoxaline termini significantly enhances the polymer's conjugation and planarity, thereby facilitating more efficient charge transport. The fabricated polymer memristor with the structure of Al/PBDTT-BPQTPA/ITO exhibits typical non-volatile resistive switching behavior under high voltage conditions, along with history-dependent memristive properties at lower voltages. The unique memristive behavior of the device enables the simulation of synaptic enhancement/inhibition, learning algorithms, and memory operations. Additionally, the memristor demonstrates its capability for executing logical operations and handling decimal calculations. This study offers a promising and innovative approach for the development of artificial neuromorphic computing systems.

Paternal preconception alcohol consumption increased Angiotensin II-mediated vasoconstriction in male offspring cerebral arteries via oxidative stress-AT1R pathway.

Alcohol consumption is popular worldwidely and closely associated with cardiovascular diseases. Influences of paternal preconception alcohol consumption on offspring cerebral arteries are largely unknown. Male rats were randomly given alcohol or water before being mated with alcohol-naive females to produce alcohol- and control-sired offspring. Middle cerebral artery (MCA) was tested with a Danish Myo Technology wire myograph, patch-clamp, IONOPTIX, immunofluorescence and quantitative PCR. Alcohol consumption enhanced angiotensin II (AngII)-mediated constriction in male offspring MCA mainly via AT1R. PD123,319 only augmented AngII-induced constriction in control offspring. AngII and Bay K8644 induced stronger intracellular calcium transient in vascular smooth muscle cells (VSMCs) from MCA of alcohol offspring. L-type voltage-dependent calcium channel (L-Ca2+ ) current at baseline and after AngII-stimulation was higher in VSMCs. Influence of large-conductance calcium-activated potassium channel (BKC a ) was lower. Caffeine induced stronger constriction and intracellular calcium release in alcohol offspring. Superoxide anion was higher in alcohol MCA than control. Tempol and thenoyltrifluoroacetone alleviated AngII-mediated contractions, while inhibition was significantly higher in alcohol group. The mitochondria were swollen in alcohol MCA. Despite lower Kcnma1 and Prkce expression, many genes expressions were higher in alcohol group. Hypoxia induced reactive oxygen species production and increased AT1R expression in control MCA and rat aorta smooth muscle cell line. In conclusion, this study firstly demonstrated paternal preconception alcohol potentiated AngII-mediated vasoconstriction in offspring MCA via ROS-AT1R. Alcohol consumption increased intracellular calcium via L-Ca2+ channel and endoplasmic reticulum and decreased BKCa function. The present study provided new information for male reproductive health and developmental origin of cerebrovascular diseases.

Predictive nomogram for hearing deficits after microvascular decompression treatment.

We explored the impact of brainstem auditory evoked potentials monitoring, as well as anatomical characteristics, in relation to their influence on hearing deficits. A total of 851 patients diagnosed with idiopathic hemifacial spasm underwent microvascular decompression treatment were recruited in our study. A nomogram was developed based on the regression analysis. Nomogram performance was evaluated through receiver operating characteristic (ROC), decision curve analyses and calibration curve. The rate of positive wave V change was also higher in the hearing deficit group (71.8% vs no hearing deficit group, p < 0.001). Furthermore, greater retraction depth (0.78 ± 0.25 cm vs 0.55 ± 0.12 cm, p < 0.001), duration (74.43 ± 15.74 min vs 55.71 ± 7.01 min, p < 0.001) and retraction distance (4.38 ± 0.38 cm vs 4.17 ± 0.24 cm, p = 0.001) were evident in the hearing deficit patients. Multivariate logistic regression showed that positive wave V change (OR 5.43), greater retraction depth (OR 55.57) and longer retraction duration (OR 1.14) emerged as significant independent predictors of postoperative hearing deficit. The external validation cohort exhibited a favorable discrimination with an AUC of 0.88. The calibration curves further confirmed the reliability of the predicted outcome in relation to the observed outcome in the external validation cohort (p = 0.89). The decision curves demonstrated that the nomogram outperformed the All or None scheme when the threshold probability ranged from > 2% to < 60% in the external validation cohort. We constructed a nomogram, including wave V, retraction depth, and retraction duration, which can effectively predict the occurrence of hearing deficits and has good clinical applicability.

Copper-Based Metal-Organic Framework Enables ROS Amplification and Drug Potency Activation.

Reactive oxygen species (ROS)-induced cancer therapy is extremely limited by tumor hypoxia, insufficient endogenous hydrogen peroxide (H2O2), overexpressed glutathione (GSH), and slower reaction rate. To address these challenges, in this paper, a hybrid nanomedicine (CaO2@Cu/ZIF-8-ICG@LA, CCZIL) is developed using a copper-based metal-organic framework (Cu/ZIF-8) for cancer synergistic therapy. H2O2/O2 self-supplementing, GSH-depleting, and photothermal properties multiply amplify ROS generation. Moreover, disulfiram (DSF) chemotherapy (CT) was activated by chelating with Cu2+ to synergize therapy. This novel strategy has enormous potential for ROS-involved synergistic antitumor therapy.

Evidence-based Practice of Preparing the Best Evidence for Intestinal Tract in Elderly Patients Before Colonoscopy.

Context: Adequate intestinal preparation is the key to colonoscopies. The population of older adults in China is developing rapidly, and their incidence of intestinal lesions is relatively high. The failure rate of intestinal preparation of these older adults is high. Objective: The study intended to develop and implement an evidence-based practice program, based on the best evidence available and combined with information about an endoscopy center's clinical situation, to improve the qualified rate and quality of the intestinal preparation of older patients and to reduce the waste of medical resources. Design: Using the method of evidence-based nursing, the research team performed a literature search for the relevant guidelines for intestinal preparation for colonoscopies, developed a program using evidence-based practices, and conducted a prospective study using the indicators developed. Setting: The study took place at the Center for Digestive Endoscopy at Shanxi Provincial People's Hospital, a Grade-3A hospital, in Taiyuan City, Shanxi Province, China. Participants: Participants were 120 older adults who underwent a colonoscopy between July and September 2021 and 60 older patients who did so between October and December 2021. The patients from July through September became the baseline group, and the patients from October through October became the postintervention group. Outcome Measures: Set up an evidence-based practice group that included an evidence-based expert group and a review team, with members from the Center for Digestive Endoscopy. The practice group: (1) performed a literature review and developed the review's content; (2) conducted a baseline review of the endoscopy center's nursing procedures; (3) analyzed the promoting and hindering factors based on the review's results; (3) conducted a study with older adult patients that compared the changes between baseline and postintervention in the qualified rate of intestinal-preparation cleanliness, dietary restrictions during intestinal preparation, and the compliance rate for medications and exercise; and (4) measured patients' incidence of adverse reactions and the nurses' implementation rate of intestinal-preparation education. Results: The postintervention group's qualified rate of intestinal cleanliness, at 48 participants (80%), was significantly higher than that of the baseline group, at 35 participants (58.3%), with P = .010. For the intestinal preparation, the postintervention group's compliance with dietary restrictions, use of medications, and performance of exercise was significantly higher than that of the baseline group (all P < .001). The postintervention group's incidence of adverse reactions, such as abdominal distension, was significantly lower (P < .05), while the incidence of abdominal pain, headache, dizziness, and other adverse reactions were significantly different between the groups (P > .05). At baseline, the implementation rate by nursing staff in the endoscopic center for the baseline group was less than 50% for four indicators, but the implementation rate for the postintervention group for those indicators was significantly higher (P < .05). Conclusions: The best evidence for methods of intestinal preparation effectively reduced the adverse reactions of older patients and improved their compliance and the cleanliness of the intestinal preparation. The management of intestinal preparation using an evidence-based nursing practice can effectively standardize the process of intestinal preparation before colonoscopies and improve the cleanliness of and patients' compliance with intestinal preparation.

Design, Synthesis, Biological Evaluation and Molecular Docking Studies of Quercetin-Linker-H2 S Donor Conjugates for the Treatment of Diabetes and Wound Healing.

Based on the use of quercetin for treating diabetes and H2 S for promoting wound healing, a series of three quercetin-linker-H2 S donor conjugates was designed, synthesized and characterized by 1 H-NMR, 13 C-NMR and MS. Meanwhile, in vitro evaluation of these compounds was also researched by IR-HepG2 treatment experiment, MTT assay, scratch test and tubule formation experiment. The three compounds could be used to treat insulin resistance induced by high glucose and promote the proliferation of human umbilical vein endothelial cells, wound healing, and the formation of tubules in vitro under a high-glucose environment. Our results illustrate that these compounds could be used to treat diabetes and promote wound healing at the same time. Furthermore, molecular docking study results of the compounds were consistent with the evaluated biological activity. In vivo research of compounds is underway.

Competitive fluorescent immunoassay for the ultrasensitive determination of amyloid beta peptide1-42 based on Ag@SiO2@N, S-GQD nanocomposites.

A competitive fluorescent immunoassay is described for the ultrasensitive determination of amyloid beta peptide1-42 (Aß1-42), a biomarker for early diagnosis of Alzheimer's disease. N, S-doped graphene quantum dots (N, S-GQDs) were freely assembled on the surface of Ag@SiO2 nanoparticles to obtain a composite (Ag@SiO2@N, S-GQD nanocomposite), which was successfully prepared and characterized. By theoretical study, the optical properties of nanocomposites are improved compared with GQDs, due to the advantages of combining N, S co-doping and metal-enhanced fluorescence (MEF) effect of Ag NPs. In addition, Aß1-42 was modified by Ag@SiO2@N, S-GQDs to prepare a probe with high photoluminescence properties (Ag@SiO2@N, S-GQDs-Aß1-42). In the presence of Aß1-42, a competitive reaction towards anti-Aß1-42 fixed on the ELISA plate was proceeded between Aß1-42 and Ag@SiO2@N, S-GQDs-Aß1-42 by specific capture of antigen-antibody. The emission peak of Ag@SiO2@N, S-GQDs-Aß1-42 (400 nm emission) was used for the quantitative determination of Aß1-42. Under the optimal conditions, the fluorescent immunoassay exhibited a linear range of 0.32 pg·mL-1-5 ng·mL-1 with a detection limit of 0.098 pg·mL-1. The results show that the immunoassay has good analytical ability and can provide a new method for the clinical determination of Aß1-42.

Selective Delivery of Tofacitinib Citrate to Hair Follicles Using Lipid-Coated Calcium Carbonate Nanocarrier Controls Chemotherapy-Induced Alopecia Areata.

Chemotherapy-induced alopecia (CIA) is one of the common side effects in cancer treatment. The psychological distress caused by hair loss may cause patients to discontinue chemotherapy, affecting the efficacy of the treatment. The JAK inhibitor, Tofacitinib citrate (TFC), showed huge potential in therapeutic applications for treating baldness, but the systemic adverse effects of oral administration and low absorption rate at the target site limited its widespread application in alopecia. To overcome these problems, we designed phospholipid-calcium carbonate hybrid nanoparticles (PL/ACC NPs) for a topical application to target deliver TFC. The results proved that PL/ACC-TFC NPs showed excellent pH sensitivity and transdermal penetration in vitro. PL/ACC NPs offered an efficient follicular targeting approach to deliver TFC in a Cyclophosphamide (CYP)-induced alopecia areata mouse model. Compared to the topical application of TFC solution, PL/ACC-TFC NPs significantly inhibited apoptosis of mouse hair follicles and accelerated hair growth. These findings support that PL/ACC-TFC NPs has the potential for topical application in preventing and mitigating CYP-induced Alopecia areata.

A comprehensive evaluation of pre- and post-processing sperm parameters for predicting successful pregnancy rate following intrauterine insemination with the husband's sperms.

BACKGROUND: To determine the predictive values of sperm parameters pre- and post-processing by density gradient centrifugation for clinical pregnancy rates (CPRs) following artificial insemination by husband (AIH) in infertile Chinese couples. METHODS: A total of 3,522 AIH cycles from 1,918 couples were retrospectively analyzed. The parameters were compared between the pregnant and non-pregnant groups and further between different etiological groups (Male-factor, Both-male-and-female-factor, and Other-factor). Multivariate logistic regression analysis was performed to create models for predicting the CPRs of each etiological group. RESULTS: The overall CPR was 13.3%. There were significant improvements for most sperm parameters after DGC. Multivariate logistic regression analysis indicated that, in overall AIH cases, the top parameters significantly influencing the CPR of AIH were pre-STR (OR = 1.037; P = 0.048) and post-VSL (OR = 1.036; P = 0.011). In the Male-factor Group, the top influencing parameters were pre-VCL (OR = 2.096; P = 0.008), pre-LIN (OR = 1.930; P = 0.002) and post-VSL (OR = 1.316; P = 0.023). In the Both-factor Group, the top influencing parameters were pre-VCL (OR = 1.451; P = 0.008) and post-motility (OR = 1.218; P = 0.049). In the Other-factor Group, the top influencing parameters were pre-VAP (OR = 1.715; P = 0.024), pre-STR (OR = 1.20; P = 0.011) and post-VSL (OR = 1.04; P = 0.017). Moreover, receiver operating characteristic analysis showed that the logistic regression models of the Male- and Both-factor Groups had greater powers for prognostic classification than those of other groups. CONCLUSIONS: This study demonstrated that some sperm parameters have a collinearity relationship in predicting the CPR following AIH. Moreover, the predictive capacity of a multivariate logistic regression model is better than those of individual parameters, especially for the Male- and Both-factor Groups. In these cases, pre-VCL is the common top influencing factor.

Prognostic nomogram for percutaneous balloon compression in the treatment of trigeminal neuralgia.

Because of its convenience and safety, percutaneous balloon compression (PBC) has become a more popular remedy for trigeminal neuralgia (TN) recently. The objective of this study was to establish a nomogram that can be used to preoperatively prognosticate the likelihood of pain-free based on preoperative disease characteristics. Clinical data were collected from those TN cases who had undergone PBC during the period of 2015 and 2020 in Qingdao Municipal Hospital. We excluded the cases caused by space-occupying lesion or had undergone MVD, percutaneous glycerol rhizotomy (PGR), and glycerol rhizotomy (GR). A nomogram was established based on the results of multivariable logistic analysis. A receiver operating characteristic curve (ROC) analysis was applied to evaluate the reliability of models. The plotted decision curves were also used to assess the net benefit of nomogram-assisted decisions. Internal validation was performed using the ROC by bootstrap sampling. Finally, 16 cases and 69 cases were included into the ineffective and effective groups respectively. In the crude, adjust I and adjust II models, response to carbamazepine positively, the grade II or III compression severity score, and classical TN type were all considered to be significant predictors of pain relief (BNI grades I-III) at 3 months' follow-up. The AUC, accuracy, specificity, and sensitivity of the nomogram system were 0.83, 0.85, 0.75, and 0.87 respectively for predicting patient outcomes. The decision curves showed good performance for the nomogram system in terms of clinical application, while more research with validation in multiple, external independent patient populations is needed.

Predictive nomogram for deep brain stimulation-related infections.

OBJECTIVE: Infection is one of the important and frequent complications following implantable pulse generator and deep brain stimulation (DBS) electrode insertion. The goal of this study was to retrospectively evaluate and identify potential risk factors for DBS infections. METHODS: From January 2015 to January 2021 in Qingdao municipal hospital (training cohort) and The First Affiliated Hospital of the University of Science and Technology of China (validation cohort), the authors enrolled patients with Parkinson disease who had undergone primary DBS placement or implantable pulse generator replacement. The cases were divided into infection or no-infection groups according to the 6-month follow-up. The authors used the logistic regression models to determine the association between the variables and DBS infection. Depending on the results of logistic regression, the authors established a nomogram. The calibration curves, receiver operating characteristic curve analysis, and decision curves were used to evaluate the reliability of the nomogram. RESULTS: There were 191 cases enrolled in the no-infection group and 20 cases in the infection group in the training cohort. The univariate logistic regression showed that BMI, blood glucose, and albumin were all significant predictors of infection after DBS surgery (OR 0.832 [p = 0.009], OR 1.735 [p < 0.001], and OR 0.823 [p = 0.001], respectively). In the crude, adjust I, and adjust II models, the three variables stated above were all considered to be significant predictors of infection after DBS surgery. The calibration curves in both training and validation cohorts showed that the predicted outcome fitted well to the observed outcome (p > 0.05). The decision curves showed that the nomogram had more benefits than the "All or None" scheme. The areas under the curve were 0.93 and 0.83 in the training and validation cohorts, respectively. CONCLUSIONS: The nomogram included BMI, blood glucose, and albumin, which were significant predictors of infection in patients with DBS surgery. The nomogram was reliable for clinical application.

A Nomogram for Predicting Acute Respiratory Failure After Cervical Traumatic Spinal Cord Injury Based on Admission Clinical Findings.

OBJECTIVES: Acute respiratory failure (ARF) is a common medical complication in patients with cervical traumatic spinal cord injury (TSCI). To identify independent predictors for ARF onset in patients who underwent cervical TSCI without premorbid respiratory diseases and to apply appropriate medical supports based on accurate prediction, a nomogram relating admission clinical information was developed for predicting ARF during acute care period. METHODS: We retrospectively reviewed clinical profiles of patients who suffered cervical TSCI and were emergently admitted to Qingdao Municipal Hospital from 2014 to 2020 as the training cohort. Univariate analysis was performed using admission clinical variables to estimate associated factors and a nomogram for predicting ARF occurrence was generated based on the independent predictors from multivariate logistic regression analysis. This nomogram was assessed by concordance index for discrimination and calibration curve with internal-validated bootstrap strategy. Receiver operating characteristic curve was conducted to compare the predictive accuracy between the nomogram and the traditional gold standard, which combines neuroimaging and neurological measurements by using area under the receiver operating characteristic curve (AUC). An additional 56-patient cohort from another medical center was retrospectively reviewed as the test cohort for external validation of the nomogram. RESULTS: 162 patients were eligible for this study and were included in the training cohort, among which 25 individuals developed ARF and were recorded to endure more complications. Despite the aggressive treatments and prolonged intensive care unit cares, 14 patients insulted with ARF died. Injury level, American Spinal Injury Association Impairment Scale (AIS) grade, admission hemoglobin (Hb), platelet to lymphocyte ratio, and neutrophil percentage to albumin ratio (NPAR) were independently associated with ARF onset. The concordance index of the nomogram incorporating these predictors was 0.933 in the training cohort and 0.955 in the test cohort, although both calibrations were good. The AUC of the nomogram was equal to concordance index, which presented better predictive accuracy compared with previous measurements using neuroimaging and AIS grade (AUC 0.933 versus 0.821, Delong's test p < 0.001). Similar significant results were also found in the test cohort (AUC 0.955 versus 0.765, Delong's test p = 0.034). In addition, this nomogram was translated to a Web-based calculator that could generate individual probability for ARF in a visualized form. CONCLUSIONS: The nomogram incorporating the injury level, AIS grade, admission Hb, platelet to lymphocyte ratio, and NPAR is a promising model to predict ARF in patients with cervical TSCI who are absent from previous respiratory dysfunction. This nomogram can be offered to clinicians to stratify patients, strengthen evidence-based decision-making, and apply appropriate individualized treatment in the field of acute clinical care.

A New 7-Azaindole Structure Analog: Molecular Docking, Synthesis and Preliminary Biological Activity in Vitro for Anticancer.

In this work, a series of 7-azaindole analogs were designed by the bioisosteric principle based on the pharmacodynamic parent nucleus. Moreover, 5-[(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]-N-{[6-(trifluoromethyl)pyridin-3-yl]methyl}pyrimidin-2-amine (compound P1) with the strongest interaction with colony-stimulating factor 1 receptor (CSF-1R) was screened by molecular docking. Compound P1 was successfully prepared by the six-step reaction with HPLC purity of 99.26 % and characterized by 1 H-NMR and ESI-MS spectra. In vitro bioactivity study showed that compound P1 appeared the cytotoxicity to MCF-7 and A549 cells, especially to HOS cells (IC50 =88.79±8.07 nM), while it had lower toxicity to normal L929 cells (IC50 =140.49±8.03 µM). In addition, compound P1 could induce HOS cell death by apoptosis and blocking the G0/G1 phase at nanomolar concentrations. The obtained results indicated that compound P1 might be a promising candidate compound for anticancer drug.

Not using a tourniquet is superior to tourniquet use for high tibial osteotomy: a prospective, randomised controlled trial.

PURPOSE: Tourniquets are routinely used in high tibial osteotomy (HTO). However, research on the necessity of tourniquets during HTO is lacking. This study was designed to investigate the necessity of tourniquets in HTO. METHODS: This was a prospective study that included patients who underwent HTO at the same hospital. The patients were randomised into Group A (non-tourniquet, n = 45) and Group B (tourniquet, n = 45). Same surgical techniques and haemostatic methods were used in the two groups. RESULTS: All patients were followed up for more than three months. There was no difference in operation time, and no intra-operative vascular or nerve damage occurred in either group. The hospital stay was shorter in group A than in group B (p < 0.05). There was no difference in post-operative blood loss, haemoglobin or haematocrit (p > 0.05). The post-operative visual analogue scale (VAS) pain scores and calf swelling were lower in group A (p < 0.05), and the early knee range of motion was higher in group A (p < 0.05). The use of morphine and the incidence of thigh complications were also lower in group A (p < 0.05). There was no difference in the VAS and knee function between the two groups at three months post-operatively (p > 0.05). CONCLUSION: Tourniquet use during HTO does not reduce post-operative blood loss, operation time or intra-operative complications, but not using a tourniquet shortens the hospital stay and reduces the post-operative usage of morphine and tourniquet-related complications, which promotes early recovery of knee function.

Glaesserella parasuis serotype 4 HPS4-YC disrupts the integrity of the swine tracheal epithelial barrier and facilitates bacterial translocation.

Glaesserella parasuis (G. parasuis) is a commensal bacterium in the upper respiratory tract of pigs that can also cause the swine Glässer disease, which induces an intensive inflammatory response and results in significant economic losses to the swine industry worldwide. G. parasuis can cause disease through infection of the respiratory tract, resulting in systemic infection, but the mechanism is largely unknown. Recently we showed that Glaesserella parasuis serotype 4 (GPS4) increased swine tracheal epithelial barrier permeability, resulting in easier bacterial translocation. Tight junction proteins (TJ) play a crucial role in maintaining the integrity and impermeability of the epithelial barrier. GPS4 decreased the expression of the TJ ZO-1 and occludin in swine tracheal epithelial cells (STEC). Furthermore, the proinflammatory cytokines IL-6, IL-8 and TNF-α were significantly upregulated in GPS4-infected STEC, and both the MAPK and NF-κB signaling pathways were activated and contributed to the expression of TNF-α. We demonstrate that the production of proinflammatory cytokines, especially TNF-α, during GPS4 infection was involved in barrier dysfunction. Additionally, animal challenge experiments confirmed that GPS4 infection downregulated TJ in the lungs of piglets and induced a severe inflammatory response. In general, G. parasuis infection downregulated the expression of TJ and induced massive secretion of proinflammatory cytokines, resulting in epithelial barrier disruption and favoring bacterial infection. This study allowed us to better understand the mechanism by which G. parasuis crosses the respiratory tract of pigs.

Hyaluronic acid-functionalized redox responsive immunomagnetic nanocarrier for circulating tumor cell capture and release.

Detection of circulating tumor cells (CTCs) in peripheral blood holds significant insights for cancer diagnosis, prognosis evaluation, and precision medicine. To efficiently capture and release CTCs with high viability, we reported the development of hyaluronic acid (HA)-functionalized redox responsive immunomagnetic nanocarrier (Fe3O4@SiO2-SS-HA). First, Fe3O4nanoparticles were prepared and modified with tetraethyl orthosilicate (TEOS), 3-mercaptopropyltrimethoxysilane (MPTMS) and 2,2'-dithiodipyridine (DDPy) to form the magnetic substrate (Fe3O4@SiO2-SSPy). Modified with targeted segment HA-functionalized L-cysteine ethyl ester hydrochloride (HA-Cys) via disulfide exchange reaction, the Fe3O4@SiO2-SS-HA was formed. The nanocarrier with prominent magnetic property, targeting ligand, and redox-sensitive disulfide linkages was able to specially capture MCF-7 cells with an efficiency of 92% and effectively release captured cells with an efficiency of 81.4%. Furthermore, the Fe3O4@SiO2-SS-HA could successfully be used for the capture of MCF-7 cells, and the captured cells could be diferntiated from the blood cells. Almost all of released tumor cells kept good viability and a robust proliferative capacity after being re-cultured. It is likely that the as-prepared nanocarrier will serve as a new weapon against CD44 receptor-overexpressed cancer cells.

TOB1 modulates the decidualization of human endometrial stromal cells via the Notch pathway.

BACKGROUND: Decidualization is critical for embryo implantation and the success of pregnancy; however, the mechanisms underlying this process remain largely unknown. MATERIALS AND METHODS: In the present study, RNA sequencing was used to detect the expression levels of transducer of ERBB2/1(TOB1) in endometrial samples derived from proliferative and secretory phases. A decidualization model was induced using the combination of estrogen (E2) and progestin (P4) in human endometrial stromal cells (HESCs). The cell counting kit-8 assay was used to detect the viability of HESCs. Related proteins were detected by qPCR and western blot. RESULT: The results indicated that TOB1 expression was upregulated in the secretory endometrial samples compared with the corresponding expression observed in the proliferative samples. The expression levels of TOB1 and Notch1 were markedly increased in E2P4-treated HESCs compared with those in the control cells. Treatment with E2P4 strongly suppressed the proliferation of HESCs and induced a G1-phase cell cycle arrest. These effects were abolished by knockdown of TOB1 or treatment with of the cells with the Notch inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester. CONCLUSIONS: Therefore, these findings highlighted an important role for TOB1/Notch signaling in E2P4-induced decidualization in HESCs, which may provide novel targets for improving the endometrial receptivity.