Ceftazidime-Avibactam Combination Therapy versus Monotherapy for the Treatment Carbapenem-Resistant Gram-Negative Bacterial Infections: A Retrospective Observational Study.

Purpose: Since the introduction of ceftazidime-avibactam (CZA) in the Chinese market, accumulating clinical evidence has substantiated its efficacy in the treatment of infections caused by carbapenem-resistant gram-negative bacteria (CR-GNB). Nevertheless, an ongoing debate persists concerning the choice between monotherapy and combination therapy when devising clinical anti-infection protocols. Patients and Methods: This retrospective, single-center observational study enrolled patients with CR-GNB infections who received CZA treatment between December 2019 and August 2023. The primary outcome assessed was 30-day mortality, and the secondary outcome measured was 14-day bacterial clearance. A multivariate Cox regression model was used to identify variables that were independently associated with 30-day mortality rate. Results: Eighty-three patients were enrolled in the study; of which, 45 received CZA monotherapy, whereas 38 received combination therapy. The overall 30-day mortality rate was 31.3%, and no significant difference was observed in the 30-day mortality rates between the CZA combination therapy and monotherapy groups (31.6% vs 31.1%, p=0.963). After adjustment by propensity score matching, the 30-day mortality rate was not significantly different between the two groups (28.6% vs 31.4%, p=0.794). Multivariate COX analysis revealed that age and SOFA score were independent predictors of 30-day mortality. Conclusion: Combination therapy with CZA and other antimicrobials was not found to have an advantage over monotherapy in reducing the 30-day mortality rate.

Effects of Nanomaterials on Synthesis and Degradation of the Extracellular Matrix.

Extracellular matrix (ECM) remodeling is accompanied by the continuous synthesis and degradation of the ECM components. This dynamic process plays an important role in guiding cell adhesion, migration, proliferation, and differentiation, as well as in tissue development, body repair, and maintenance of homeostasis. Nanomaterials, due to their photoelectric and catalytic properties and special structure, have garnered much attention in biomedical fields for use in processes such as tissue engineering and disease treatment. Nanomaterials can reshape the cell microenvironment by changing the synthesis and degradation of ECM-related proteins, thereby indirectly changing the behavior of the surrounding cells. This review focuses on the regulatory role of nanomaterials in the process of cell synthesis of different ECM-related proteins and extracellular protease. We discuss influencing factors and possible related mechanisms of nanomaterials in ECM remodeling, which may provide different insights into the design and development of nanomaterials for the treatment of ECM disorder-related diseases.

Effect of Brucea javanica Oil on the Toxicity of ß-Cypermethrin Emulsifiable Concentrate Formulation.

Enhancing the performance of traditional pesticide formulations by improving their leaf surface wetting capabilities is a crucial approach for maximizing the pesticide efficiency. This study develops an emulsifiable concentrate (EC) of 4.5% ß-cypermethrin containing Brucea javanica oil (BJO). The incorporation of BJO aims to improve the leaf-wetting properties of the EC formulation and enhance its insecticidal effectiveness. The droplet size and emulsion characteristics of ß-CYP EC emulsion with varying concentrations of the emulsifier were evaluated, and changes after incorporating BJO were assessed to develop the optimal formulation. A comprehensive comparison was conducted among commercial 4.5% ß-cypermethrin EC (ß-CYP EC-1), 4.5% ß-cypermethrin EC with BJO (ß-CYP EC-2), and 4.5% ß-cypermethrin EC without BJO (ß-CYP EC-3). This comparison encompassed various factors including storage stability, insecticidal activity, cytotoxicity, and wetting performance on cabbage leaves. The results indicated that the ideal emulsifier concentration was 15% emulsifier 0201B. ß-CYP EC-2 demonstrated superior wetting properties on cabbage leaves (the wetting performance of ß-CYP EC-2 emulsion on cabbage leaves is 2.60 times that of the ß-CYP EC-1 emulsion), heightened insecticidal activity against the third larvae of Plutella xylostella [diamondback moth (DBM)] [the insecticidal activity of the ß-CYP EC-2 emulsion against the third larvae of DBM is 1.93 times that of the ß-CYP EC-1 emulsion (12 h)], and more obvious inhibitory effects on the proliferation of DBM embryo cells than the other tested formulations. These findings have significant implications for advancing pest control strategies and promoting sustainable and effective agricultural practices.

Clinical effect of acupoint application with turmeric blistering moxibustion plaster on post-stroke hemiplegic shoulder pain. / 姜黄天灸膏穴位贴敷治疗脑卒中偏瘫肩痛临床疗效观察.

OBJECTIVES: To observe the effects of acupoint application with turmeric blistering moxibustion plaster on pain, shoulder range of motion (ROM) and upper limb motor function in the patients with post-stroke hemiplegic shoulder pain (PSHSP). METHODS: Eighty-two patients with PSHSP were randomly divided into an observation group (41 cases, 1 case was eliminated, 4 cases dropped out) and a control group (41 cases, 2 cases were eliminated and 2 cases dropped out). The routine treatment, nursing care and rehabilitation training were performed in the control group. On the basis of the intervention as the control group, in the observation group, the turmeric blistering moxibustion plaster was applied to bilateral ashi points, Jianyu (LI 15), Jianliao (TE 14), Binao (LI 14), Shousanli (LI 10) and Hegu (LI 4), once a day, remained for 6 hours each time. This moxibustion therapy was operated 5 times weekly, one course of treatment consisted of 2 weeks and 2 courses were required. Separately, before treatment and after 2 and 4 weeks of treatment, the score of visual analogue scale (VAS), shoulder ROM and the score of upper limbs in Fugl-Meyer assessment (U-FMA) were observed in the two groups. RESULTS: VAS scores were lower (P<0.05), ROM in shoulder flexion, abduction, internal rotation and external rotation was larger (P<0.05), and U-FMA scores were higher (P<0.05) after 2 and 4 weeks of treatment when compared with those before treatment in the two groups. After 4 weeks of treatment, VAS score decreased (P<0.05), and ROM in shoulder flexion, abduction, internal rotation, external rotation and U-FMA score increased (P<0.05) in comparison with those after 2 weeks of treatment in either group. In the observation group, VAS scores were dropped (P<0.05) after 2 and 4 weeks of treatment respectively, and ROM of shoulder flexion and abduction enlarged after 2 weeks of treatment (P<0.05) when compared with those in the control group. After 4 weeks of treatment, ROM in shoulder flexion, abduction, internal rotation and external rotation in the observation group was larger (P<0.05) and U-FMA score was higher (P<0.05) than those in the control group. CONCLUSIONS: Acupoint application with turmeric blistering moxibustion plaster may effectively reduce the degree of shoulder pain and improve the shoulder range of motion and the upper limb motor function in the patients with post-stroke hemiplegic shoulder pain.

Risk Factors and Outcomes for Isolation with Polymyxin B-Resistant Enterobacterales from 2018-2022: A Case-Control Study.

Purpose: To analyze the risk factors and clinical outcomes of patients isolated with polymyxin B-resistant (PR) Enterobacterales from various clinical specimens to prevent and control the spread of these strains. Methods: This retrospective case-control study included 72 PR Enterobacterales-positive cases and 144 polymyxin B-susceptible (PS) Enterobacterales controls from 2018 to 2022. Patients with PR Enterobacterales isolated in various clinical cultures were defined as cases. Patients with PS Enterobacterales cultures at similar anatomic sites during the same period were randomly selected as controls. Data were collected from clinical and laboratory test records. Bivariable logistic regression and Pearson's chi-square tests were used to assess risk factors. Results: PR strains were predominantly Klebsiella pneumoniae (72.2%) and Salmonella enteritidis (8.3%). Of the patients, 66.04% were admitted to an intensive care unit (ICU). Risk factors for isolation with PR strains included chronic heart disease (P = 0.012; odds ratio [OR] 1.15; 95% confidence interval [CI] 1.03-1.28), immunosuppressant use (P = 0.016; OR 1.04 [1.0-1.07), drainage tube [head] (P = 0.006; OR 1.1 [1.0-1.1]), and polymyxin B exposure (P = 0.007; OR 1.03 [1.0-1.06]. With respect to outcomes, admission to an ICU (P = 0.003; OR 7.1 [1.9-25.4]), hypertension (P = 0.035; OR 1.4 [1.02-1.83]), and drainage tube [head] (P = 0.044; OR 1.1 [1.0-1.15]) were associated with treatment failure. Additionally, treatment failure was more frequent in patients (45.83%) than in controls (14.58%). Conclusion: The major risk factors for isolation with PR strains were chronic heart disease, exposure to immunosuppressants, use of drainage tubes, and polymyxin B exposure. The isolation of PR strains in patients was a predictor of unfavorable outcomes. These findings provide a basis for monitoring the spread of PR Enterobacterales.

Green synthesis of a chlorfenapyr chitosan nanopesticide for maize root application: Reducing environmental pollution and risks to nontarget organisms.

Chlorfenapyr (CHL) is a pyrrole insecticide with a novel structure that is used to control resistant pests. However, its weak systemic activity limits its application to crop roots. Herein, a novel CHL formulation with improved effective utilization rates and suitability for root application is developed to avoid or reduce contamination caused by pesticide spraying. Accordingly, we prepared CHL@CS/CMCS nanoparticle (NP) suspensions with a particle size of approximately 100 nm using chitosan (CS) and carboxymethyl chitosan (CMCS). These suspensions exhibited better thermal stability, adhesion, permeability and systemic activity than a CHL suspension concentrate (CHL-SC). The nanoformulation deposition rate on maize leaves after spraying was 12.28 mg/kg, significantly higher than that of CHL-SC. The nanosuspension was effectively absorbed and transported by roots after irrigation and was suitable for root application. The efficacy was 89.46-92.36 % against Spodoptera frugiperda at 7 d, 7.5-17.5 times higher than that of CHL-SC. Furthermore, the CHL@CS/CMCS nanosuspension was safer for earthworms. These results suggest that chitosan-based nanoformulations improve the efficacy, utilization efficiency and active period of CHL control, providing a new approach for CHL application, reducing pollutant dispersal and the environmental impacts of pesticide application and facilitating sustainable agricultural production.

Human Parathyroid Hormone Analog (3-34/29-34) promotes wound re-epithelialization through inducing keratinocyte migration and epithelial-mesenchymal transition via PTHR1-PI3K/AKT activation.

BACKGROUND: Re-epithelialization is important in the process of wound healing. Various methods have been identified to expedite the process, but their clinical application remains limited. While parathyroid hormone (PTH) has shown promising results in wound healing due to its role in promoting collagen deposition and cell migration, application is limited by its potentially inhibitive effects when being continuously and locally administrated. Herein, we developed a novel PTH analog, Human parathyroid hormone (hPTH) (3-34/29-34) (henceforth MY-1), by partially replacing and repeating the amino acid sequences of hPTH (1-34), and evaluated its effect on skin wound re-epithelialization. METHODS: CCK-8, colony formation unit assay, and Ki67 immunofluorescent staining were performed to evaluate the effect of MY-1 on HaCaT cell proliferation. Then, wound scratch assay, Transwell assay and lamellipodia staining were carried out to evaluate the effect of MY-1 on cell migration. Moreover, the epithelial-mesenchymal transition (EMT) markers were measured using qPCR and western blot analysis. For in-vivo drug delivery, gelatin methacryloyl (GelMA) hydrogel was employed to load the MY-1, with the physicochemical characteristics evaluated prior to its application in wound models. Then, MY-1's role in wound healing was determined via acute skin wound models. Finally, the mechanism that MY-1 activated was also detected on HaCaT cells and in-vivo wound models. RESULTS: In-vitro, MY-1 accelerated the migration and EMT of HaCaT cells, while having little effect on cell proliferation. GelMA and MY-1-incorporated GelMA hydrogels showed similar physicochemical characteristics and were used in the in-vivo studies, where the results revealed that MY-1 led to a stronger re-epithelialization by inducing basal keratinocyte migration and EMT. Further studies on in-vivo wound models and in-vitro HaCaT cells revealed that MY-1 regulated cell migration and EMT through activating PI3K/AKT signaling. The parathyroid hormone type 1 receptor (PTHR1), the main receptor of PTH, was found to be the upstream of PI3K/AKT signaling, through interfering PTHR1 expression with a small interference RNA following detection of the PI3K/AKT activation. CONCLUSION: Collectively, our study demonstrated that MY-1 accelerates skin wound re-epithelialization by inducing keratinocyte migration and EMT via PTHR1-PI3K/AKT axis activation. Video Abstract.

Efficacy of drip irrigation with thiamethoxam on control of Monolepta hieroglyphica, and uptake, translocation and dietary risk of thiamethoxam in maize.

BACKGROUND: Monolepta hieroglyphica (Motschulsky) is an important agricultural pest that causes significant economic losses in terms of crop production. Conventional pesticide spraying treatments can result in pesticide drift, endanger nontarget organisms and cause pests to fly away, resulting in unsatisfactory prevention and control effects. To study the effect of thiamethoxam on the control of maize M. hieroglyphica, a field experiment was conducted to determine the optimal thiamethoxam application dose, its spatial and temporal distribution dynamics, and its dietary risk based on its control effect when applied by spray and drip irrigation. RESULTS: The results of the field trials showed that compared with spray irrigation, drip irrigation resulted in greater control starting from Day 5. This result was a consequence of the hysteresis effect of thiamethoxam being first absorbed by the roots and then continuously transferred upward, where it accumulates. After 30 days of drip irrigation with 75 and 150 g a.i. ha-1 thiamethoxam, the control effect on M. hieroglyphica was 32.41-49.44% and 69.77-80.57%, respectively. The results of the dietary risk assessment showed that the risk of thiamethoxam ingestion through maize kernels was acceptable regarding its effect on human health. CONCLUSIONS: Drip irrigation with thiamethoxam can improve the effective utilization rate of pesticides, achieve precise control of maize M. hieroglyphica, and provide a new method for sustainable agricultural production. © 2023 Society of Chemical Industry.

Impaired angiogenesis in ageing: the central role of the extracellular matrix.

Each step in angiogenesis is regulated by the extracellular matrix (ECM). Accumulating evidence indicates that ageing-related changes in the ECM driven by cellular senescence lead to a reduction in neovascularisation, reduced microvascular density, and an increased risk of tissue ischaemic injury. These changes can lead to health events that have major negative impacts on quality of life and place a significant financial burden on the healthcare system. Elucidating interactions between the ECM and cells during angiogenesis in the context of ageing is neceary to clarify the mechanisms underlying reduced angiogenesis in older adults. In this review, we summarize ageing-related changes in the composition, structure, and function of the ECM and their relevance for angiogenesis. Then, we explore in detail the mechanisms of interaction between the aged ECM and cells during impaired angiogenesis in the older population for the first time, discussing diseases caused by restricted angiogenesis. We also outline several novel pro-angiogenic therapeutic strategies targeting the ECM that can provide new insights into the choice of appropriate treatments for a variety of age-related diseases. Based on the knowledge gathered from recent reports and journal articles, we provide a better understanding of the mechanisms underlying impaired angiogenesis with age and contribute to the development of effective treatments that will enhance quality of life.

Microbiological Analysis and Mortality Risk Factors in Patients with Polymicrobial Bloodstream Infections.

Purpose: To study the etiological characteristics and risk factors affecting the prognosis of patients with polymicrobial bloodstream infections. Patients and Methods: Overall, 141 patients with polymicrobial bloodstream infections in Henan Provincial People's Hospital during 2021 were included. Laboratory test indexes, department of admission, sex, age, intensive care unit (ICU) admission, surgical history, and central venous catheter placement were collected. Patients were divided into surviving and deceased groups based on outcomes at discharge. Mortality risk factors were identified by univariate and multivariable analyses. Results: Seventy-two of 141 patients survived. Patients were mainly from the ICU and the Departments of Hepatobiliary Surgery and Hematology. Overall, 312 microbial strains were detected: 119 gram-positive, 152 gram-negative, and 13 anaerobic bacteria and 28 fungi. Among the gram-positive bacteria, coagulase-negative staphylococci were most frequent (44/119, 37%), followed by enterococci (35/119, 29.4%). Among coagulase-negative staphylococci, methicillin-resistant coagulase-negative staphylococci incidence was 75% (33/44). Among gram-negative bacteria, Klebsiella pneumoniae was most common (45/152, 29.6%), followed by Escherichia coli (25/152, 16.4%) and Pseudomonas aeruginosa (13/152, 8.6%). Among K. pneumoniae, the incidence of carbapenem-resistant (CR) K. pneumoniae was 45.7% (21/45). On univariate analysis, mortality risk factors included increased white blood cells and C-reactive protein, decreased total protein and albumin, CR strains, ICU admission, central venous catheter, multiple organ failure, sepsis, shock, pulmonary diseases, respiratory failure, central nervous system diseases, cardiovascular diseases, hypoproteinemia, and electrolyte disturbances (P < 0.05). Multivariable analysis showed that ICU admission, shock, electrolyte disorders, and central nervous system diseases were independent mortality risk factors. The survival curve shows that the survival rate of patients with polymicrobial CR bloodstream infections was lower than that of patients with polymicrobial non-CR bloodstream infections (P=0.029). Conclusion: Patients with polymicrobial bloodstream infections are typically critically ill and harbor multidrug-resistant bacteria. Thus, to minimize mortality rate in critically ill patients, changes in infectious flora should be monitored, antibiotics selected reasonably, and invasive procedures reduced.

Characteristics of humoral and cellular responses to coronavirus disease 2019 (COVID-19) inactivated vaccine in central China: A prospective, multicenter, longitudinal study.

Introduction: In China, the long-term immunogenicity and adverse effects of inactivated vaccines produced by different or the same manufacturer remain unclear. Therefore, the objective of this study was to evaluate the cellular immune responses and neutralizing antibody kinetics of homologous and heterologous administrations of an inactivated coronavirus disease 2019 (COVID-19) vaccine 240 days after the second vaccination. Methods: This prospective, multicenter, observational, longitudinal study involved 595 participants with a negative SARS-CoV-2 polymerase chain reaction result who were serologically tested and followed for 8 months after vaccination. Neutralizing antibodies, interferon-gamma (IFN-γ), interleukin (IL)-6, CD4+ T-lymphocyte, and B-lymphocyte counts were evaluated in serum samples after stimulation with 2 µg/mL SARS-CoV-2 spike protein for 16 h at follow-up intervals of 2 months. Results: Most participants [582/595; 146 male participants, 449 female participants; mean age 35 (26-50 years)] rapidly developed neutralizing antibodies after two doses of the vaccine administered 3-weeks apart. The positive rate of neutralizing antibodies peaked at 97.7% at 60-90 days, decreased, and stabilized at 82.9% at 181-240 days post-vaccination. Lower antibody concentrations were correlated with older age, longer duration after vaccination, non-health care workers, mixed-manufacturer vaccinations, and intervals of less than 40 days between two doses of vaccination, whereas lower IFN-γ levels and B-lymphocyte counts were associated with older age, blood type A, and non-health care workers. A higher IL-6 level was associated with older age, mixed-manufacturer vaccinations, intervals of less than 40 days between two doses of vaccination, and medical staff. Adverse reactions were mild or moderate and self-limited, with no serious events reported. Discussion: Two doses of the Chinese inactivated vaccine induced robust and rapid antibody expression and cellular immune responses. Boosting vaccination is considered important, as antibodies and cellular immune responses were reduced in susceptible populations.

Evaluation of Commercial Products for Colistin and Polymyxin B Susceptibility Testing for mcr-Positive and Negative Escherichia coli and Klebsiella pneumoniae in China.

Purpose: To evaluate the performance of five widespread commercial products for colistin and polymyxin B susceptibility testing in China for mcr-positive and -negative Escherichia coli and Klebsiella pneumoniae. Methods: A total of 132 E. coli and 83 K. pneumoniae strains (including 68 mcr-1-positive E. coli and 28 mcr-8-positive K. pneumoniae) were collected. We analysed the performance of colistin susceptibility (with Vitek 2 and Phoenix M50) and the performance of polymyxin B susceptibility (with DL-96II, MA120, and a Polymyxin B Susceptibility Test strip; POL E-strip). Broth microdilution was used as the gold standard. Categorical agreement (CA), essential agreement (EA), major error (ME), and very major error (VME) were calculated for comparisons. Results: For E. coli, the total CA, EA, ME, and VME to colistin were as follows: Vitek 2, 98.5%/98.5%/0%/2.9%; and Phoenix M50, 98.5%/97.7%/0%/2.9%. The total CA, EA, ME, and VME to polymyxin B were as follows: POL E-strip, 99.2%/63.6%/1.6%/0%; MA120, 70.0%/-/0%/58.8%; and DL-96II, 80.2%/-/1.6%/36.8%. Only Vitek 2 and Phoenix M50 presented satisfactory performances for mcr-1-positive E. coli. For K. pneumoniae, the total CA, EA, ME, and VME to colistin were as follows: Vitek 2, 73.2%/72.0%/0%/61.6%; and Phoenix M50, 74.7%/74.7%/0%/58.3%. The total CA, EA, ME, and VME to polymyxin B were as follows: POL E-strip, 91.6%/74.7%/2.1%/16.7%; MA120, 92.8%/-/2.1%/13.9%; and DL-96II, 92.2%/-/2.1%/8.3%. All systems were unsatisfactory for mcr-8-positive K. pneumoniae. When the susceptibility of mcr-negative strains was tested, all systems presented excellent performance. Conclusion: Vitek 2 and Phoenix M50 with colistin for E. coli showed acceptable performance regardless of mcr-1 expression, while DL-96II, MA120, and the POL E-strip performed worse for mcr-1-positive strains. Furthermore, mcr-8 greatly affected the performance of all systems with both colistin and polymyxin B for K. pneumoniae isolates.

Validation of a predictive model for coronary artery disease in patients with diabetes.

BACKGROUND: No reliable model can currently be used for predicting coronary artery disease (CAD) occurrence in patients with diabetes. We developed and validated a model predicting the occurrence of CAD in these patients. METHODS: We retrospectively enrolled patients with diabetes at Henan Provincial People's Hospital between 1 January 2020 and 10 June 2020, and collected data including demographics, physical examination results, laboratory test results, and diagnostic information from their medical records. The training set included patients ( n  = 1152) enrolled before 15 May 2020, and the validation set included the remaining patients ( n  = 238). Univariate and multivariate logistic regression analyses were performed in the training set to develop a predictive model, which were visualized using a nomogram. The model's performance was assessed by area under the receiver-operating characteristic curve (AUC) and Brier scores for both data sets. RESULTS: Sex, diabetes duration, low-density lipoprotein, creatinine, high-density lipoprotein, hypertension, and heart rate were CAD predictors in diabetes patients. The model's AUC and Brier score were 0.753 [95% confidence interval (CI) 0.727-0.778] and 0.152, respectively, and 0.738 (95% CI 0.678-0.793) and 0.172, respectively, in the training and validation sets, respectively. CONCLUSIONS: Our model demonstrated favourable performance; thus, it can effectively predict CAD occurrence in diabetes patients.

Effect of virtual cement space and restorative materials on the adaptation of CAD-CAM endocrowns.

BACKGROUND: This study aimed to evaluate the effect of virtual cement space and restorative materials on the fit of computer-aided design and computer-aided manufacturing (CAD-CAM) endocrowns. METHODS: A mandibular first molar tooth model received a butt joint margin endocrown preparation with a 2-mm occlusal thickness. Then, using a 3D-printing system, 120 copies of this prepared die were printed and assigned equally to three groups with different cement space settings (30, 60, and 120 µm) during the chairside CAD design. In the milling process, CAD-based models with a particular space setting were subdivided into four groups (n = 10) and fabricated from different CAD-CAM materials: Vita Suprinity (VS), Celtra Duo (CD), Lava Ultimate (LU), and Grandio blocs (GR). Finally, the endocrowns were stabilized over their corresponding models with siloxane and subjected to micro-computed tomography to measure the fit. RESULTS: The cement space that was predesigned at 30 µm generated the largest marginal discrepancy (from 144.68 ± 22.43 µm to 174.36 ± 22.78 µm), which was significantly different from those at 60 µm and 120 µm (p < 0.001). The combination of VS or CD with a pre-setting cement space of 60 µm and the combination of LU or GR with a cement space of 120 µm showed better agreement between the predesigned and actual measured marginal gap widths. For internal adaptation, only the cement space set to 30 µm exceeded the clinically acceptable threshold (200 µm). CONCLUSIONS: The setting of the cement space and restorative material significantly affected the marginal adaptation of CAD-CAM endocrown restorations. Considering the discrepancy between design and reality, different virtual cement spaces should be applied to ceramic and resin composite materials.

Anti-Inflammatory and Mineralization Effects of an ASP/PLGA-ASP/ACP/PLLA-PLGA Composite Membrane as a Dental Pulp Capping Agent.

Dental pulp is essential for the development and long-term preservation of teeth. Dental trauma and caries often lead to pulp inflammation. Vital pulp therapy using dental pulp-capping materials is an approach to preserving the vitality of injured dental pulp. Most pulp-capping materials used in clinics have good biocompatibility to promote mineralization, but their anti-inflammatory effect is weak. Therefore, the failure rate will increase when dental pulp inflammation is severe. The present study developed an amorphous calcium phosphate/poly (L-lactic acid)-poly (lactic-co-glycolic acid) membrane compounded with aspirin (hereafter known as ASP/PLGA-ASP/ACP/PLLA-PLGA). The composite membrane, used as a pulp-capping material, effectively achieved the rapid release of high concentrations of the anti-inflammatory drug aspirin during the early stages as well as the long-term release of low concentrations of aspirin and calcium/phosphorus ions during the later stages, which could repair inflamed dental pulp and promote mineralization. Meanwhile, the composite membrane promoted the proliferation of inflamed dental pulp stem cells, downregulated the expression of inflammatory markers, upregulated the expression of mineralization-related markers, and induced the formation of stronger reparative dentin in the rat pulpitis model. These findings indicate that this material may be suitable for use as a pulp-capping material in clinical applications.

Novel application of biodegradable chitosan in agriculture: Using green nanopesticides to control Solenopsis invicta.

Botanical pesticides are biological pesticides that are environment friendly. However, their instability and short persistence limit their application. In this study, pH sensitive chitosan based rotenone (Rot) nanoparticles (CS/CMCS/Rot-NPs) were prepared using chitosan and carboxymethyl chitosan to take advantage of the acidic nature of the red fire ant midgut. Chitosan based nanoparticles showed photoprotective and slow sustained release effects on Rot and significantly increased the insecticidal activity of Rot against red fire ants. The 24-96hLC50 of CS/CMCS/Rot-NPs against red fire ants was 3.28-6.84 fold that of Rot. The CS/CMCS/Rot-NPs significantly reduced the venom alkaloid content of red fire ants and their living environment and weakened their survival by increasing their survival cost in the ecological environment. Nanotechnology combined with botanical pesticides can be used as a novel, safe, effective, and ecofriendly method to control red fire ants.

MiR-4268 suppresses gastric cancer genesis through inhibiting keratin 80.

Gastric cancer (GC) affects a large proportion of cancer patients worldwide, and the prediction of potential biomarkers can greatly improve its diagnosis and treatment. Here, miR-4268 and keratin 80 (KRT80) expression in GC tissues and cell lines was determined. The effect of downregulating miR-4268 and interfering with KRT80 expression on the viability, proliferation, apoptosis, and migration of GC cells were evaluated. The interaction between miR-4268 and KRT80 was studied using luciferase reporter and RNA pull-down assays. The western blot, CCK-8, BrdU, caspase-3 activity, Transwell assays were performed for the functional characterization. In GC tissues and cells, KRT80 expression was found to be significantly higher, while that of miR-4268 was significantly lower than the respective expressions in normal tissues and cells. Interference with KRT80 expression inhibited the viability, proliferation, and migration of GC cells and facilitated cell apoptosis in vitro. We further demonstrated that miR-4268 targeted KRT80 and negatively regulated its expression, and miR-4268 inhibitor alleviated the inhibitory effects of KRT80 downregulation on GC cell growth. Finally, miR-4268 may function as tumor suppressor through inhibiting PI3K/AKT/JNK pathways by targeting KRT80 in GC. Collectively, our present results indicate that the miR-4268/KRT80 axis acts as a potential therapeutic target for patients with GC.Abbreviations: Gastric cancer (GC); MicroRNAs (miRNAs); Keratin 80 (KRT80); differentially expressed genes (DEGs); chemoradiotherapy (CRT); negative nonsense sequence (NC); radioimmunoprecipitation assay (RIPA); polyvinylidene fluoride (PVDF).

A pH- and redox-stimulated responsive hollow mesoporous silica for triggered delivery of fungicides to control downy mildew of Luffa cylindrica.

BACKGROUND: Downy mildew, a devastating disease of cucurbitaceous crops caused by Pseudoperonospora cubensis. Although a variety of fungicides are used to control downy mildew, choosing an effective product can be challenging. Environmental stimulus-responsive pesticide delivery systems have great potential to improve the effectiveness of disease and pest control and reduce the impact on environmentally beneficial organisms. RESULTS: In this work, a disulfide bond (SS)-modified and chitosan oligosaccharide (COS)-capped hollow mesoporous silica (HMS) pesticide delivery system was synthesized using a hard template method for the control of downy mildew in cucurbit crops. The synthesized nanoparticles were loaded with dimethomorph (DMM), denoted as DMM@HMS-SS-COS, and the developmental toxicity of these nanoparticles to zebrafish embryos were evaluated. The results showed that the prepared DMM@HMS-SS-COS exhibited excellent dual response properties to pH and glutathione (GSH), with an encapsulation rate of up to 24.36%. DMM@HMS-SS-COS has good ultraviolet (UV) radiation stability and adhesion properties. Compared with dimethomorph suspension concentrate (SC), DMM@HMS-SS-COS was more effective against downy mildew for up to 21 days. Toxicity tests showed that DMM@HMS-SS-COS significantly reduced the effect of DMM on the hatching rate and survival rate of zebrafish embryos. CONCLUSIONS: This work not only demonstrates that DMM@HMS-SS-COS could be used as a nanodelivery system for intelligent control of downy mildew but also emphasizes the necessity of increasing the acute toxicity of nanoformulations to non-target organisms in environmental risk assessment. © 2022 Society of Chemical Industry.