Novel trans-Resveratrol Derivatives: Design, Synthesis, Antibacterial Activity, and Mechanisms.

Rice bacterial leaf blight and rice bacterial leaf streak have induced tremendous damage to production of rice worldwide. To discover an effective novel antibacterial agent, a series of novel trans-resveratrol (RSV) derivatives containing 1,3,4-oxadiazole and amide moieties were designed and synthesized for the first time. Most of them showed excellent antibacterial activities against Xanthomonas oryzae pv oryzicola and Xanthomonas oryzae pv oryzae. Especially, compound J12 had the best inhibitory with the half-maximal effective concentration values of 4.2 and 5.0 mg/L, respectively, which were better than that of RSV (63.7 and 75.4 mg/L), bismerthiazol (79.5 and 89.6 mg/L), and thiodiazole copper (105.4 and 112.8 mg/L). Furthermore, compound J12 had an excellent control effect against rice bacterial leaf streak and rice bacterial leaf blight, with protective activities of 46.2 and 42.1% and curative activities of 44.5 and 41.7%, respectively. Preliminary mechanisms indicated that compound J12 could not only remarkably decrease biofilm formation, extracellular polysaccharide production, and the synthesis of extracellular enzymes but also destroy bacterial cell surface morphology, thereby reducing the pathogenicity of bacteria. In addition, compound J12 could increase the activity of defense-related enzymes and affect the expression of multiple pathogenic-related genes including plant-pathogen interaction, the MAPK signaling pathway, and phenylpropanoid biosynthesis, and this could improve the defense of rice against rice bacterial leaf streak infection. The present work indicates that the RSV derivatives can be used as promising candidates for the development of antibacterial agents.

A new technique for the treatment of ureteric stricture after kidney transplantation.

OBJECTIVE: To evaluate the safety and effectiveness of endoscopic treatments with Allium® metal ureteric stent (AMUS) for ureteric strictures after kidney transplantation (KT). PATIENTS AND METHODS: In a prospective manner, we gathered clinical data from 68 patients who underwent endoscopic treatments with AMUS for ureteric strictures after KT between January 2019 and March 2022. The definition of surgical success was the unobstructed drainage of the AMUS, or in cases where there was AMUS migration, occlusion or encrustation and subsequently removed, there is no worsening of renal hydronephrosis in the patient during the follow-up period. RESULTS: Based on the specific circumstances of the ureteric strictures, three distinct types of surgery were selected for treatment. The overall success rate of endoscopic treatments for ureteric strictures following KT was 90% (61/68) during a follow-up period of 1 year. Surgical complications included haematuria (18%), pain (10%), urinary tract infections (7.4%), and lower urinary tract symptoms (7.4%). The incidences of stent migration, occlusion, and encrustation were 10%, 2.9%, and 1.5%, respectively. Postoperatively, significant improvements were observed in various parameters. At 1 month after surgery, there was a notable decrease in blood creatinine levels (105.5 vs 90.4 mol/L), urea nitrogen levels (6.6 vs 5.4 mmol/L), and hydronephrosis volume (64.4 vs 43.9 mL). Additionally, the serum estimated glomerular filtration rate increased from 49.5 to 64.4 mL/min/1.73 m2. The follow-up results of patients at 1 year after surgery were similar to those observed at 1 month after surgery. CONCLUSIONS: Systemic endoscopic treatments with AMUS were found to be safe and effective for ureteric strictures after KT with short-term follow-ups. This technique offers a novel option for the treatment of post-KT strictures.

Comparative transcriptomics revealed the mechanism of Stenotrophomonas rhizophila JC1 response and biosorption to Pb2.

Nowadays, there is limited research focusing on the biosorption of Pb2+ through microbial process, particularly at the level of gene expression. To overcome this knowledge gap, we studied the adsorption capacity of Stenotrophomonas rhizophila JC1 to Pb2+, and investigated the physiological mechanism by means of SEM, EDS, FTIR, membrane permeability detection, and investigated the molecular mechanism through comparative transcriptomics. The results showed that after 16 h of cultivation, the biosorption capacity of JC1 for 100 mg/L of Pb2+ reached at 79.8%. The main mechanism of JC1 adsorb Pb2+ is via intracellular accumulation, accounting for more than 90% of the total adsorption. At the physiological level, Pb2+ can precipitate with anion functional groups (e.g., -OH, -NH) on the bacterial cell wall or undergo replacement reaction with cell component elements (e.g., Si, Ca) to adsorb Pb2+ outside of the cell wall, thus accomplishing extracellular adsorption of Pb2+ by strains. Furthermore, the cell membrane acts as a "switch" that inhibits the entry of metal ions into the cell from the plasma membrane. At the molecular level, the gene pbt specificity is responsible for the adsorption of Pb2+ by JC1. In addition, phosphate permease is a major member of the ABC transporter family involved in Pb2+, and czcA/cusA or Co2+/Mg2+ efflux protein plays an important role in the efflux of Pb2+ in JC1. Further, cellular macromolecule biosynthesis, inorganic cation transmembrane transport, citrate cycle (TCA) and carbon metabolism pathways all play crucial roles in the response of strain JC1 to Pb2+ stress.

Exploring the multifaceted role of RASGRP1 in disease: immune, neural, metabolic, and oncogenic perspectives.

RAS guanyl releasing protein 1 (RASGRP1) is a guanine nucleotide exchange factor (GEF) characterized by the presence of a RAS superfamily GEF domain. It functions as a diacylglycerol (DAG)-regulated nucleotide exchange factor, specifically activating RAS through the exchange of bound GDP for GTP. Activation of RAS by RASGRP1 has a wide range of downstream effects at the cellular level. Thus, it is not surprising that many diseases are associated with RASGRP1 disorders. Here, we present an overview of the structure and function of RASGRP1, its crucial role in the development, expression, and regulation of immune cells, and its involvement in various signaling pathways. This review comprehensively explores the relationship between RASGRP1 and various diseases, elucidates the underlying molecular mechanisms of RASGRP1 in each disease, and identifies potential therapeutic targets. This study provides novel insights into the role of RASGRP1 in insulin secretion and highlights its potential as a therapeutic target for diabetes. The limitations and challenges associated with studying RASGRP1 in disease are also discussed.

Recent Advances and Outlook of Benzopyran Derivatives in the Discovery of Agricultural Chemicals.

Scaffold structures, new mechanisms of action, and targets present enormous challenges in the discovery of novel pesticides. The discovery of new scaffolds is the basis for the continuous development of modern agrochemicals. Identification of a good scaffold such as triazole, carbamate, methoxy acrylate, pyrazolamide, pyrido-pyrimidinone mesoionic, and bisamide often leads to the development of a new series of pesticides. In addition, pesticides with the same target, including the inhibitors of succinate dehydrogenase (SDH), oxysterol-binding-protein, and p-hydroxyphenyl pyruvate dioxygenase (HPPD), may have the same or similar scaffold structure. Recent years have witnessed significant progress in the discovery of new pesticides using natural products as scaffolds or bridges. In recent years, there have been increasing reports on the application of natural benzopyran compounds in the discovery of new pesticides, especially osthole and coumarin. A systematic and comprehensive review of benzopyran active compounds in the discovery of new agricultural chemicals is helpful to promote the discussion and development of benzopyran active compounds. Therefore, this work systematically reviewed the research and application of benzopyran derivatives in the discovery of agricultural chemicals, summarized the antiviral, herbicidal, antibacterial, fungicidal, insecticidal, nematicidal and acaricidal activities of benzopyran active compounds, and discussed the structural-activity relationship and mechanism of action. In addition, some active fragments were recommended to further optimize the chemical structure of benzopyran active compounds based on reference information.

Factor B inhibitor iptacopan for the treatment of paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, clonal, complement-mediated hemolytic anemia with a variety of manifestations. Currently, the methods for treating PNH include anti-C5 treatments (eculizumab and ravulizumab) and pegcetacoplan (a targeted C3 inhibitor). On December 5, 2023, the US FDA approved a factor B inhibitor called Fabhalta® (iptacopan), previously known as LNP023, for the treatment of adult patients with PNH, including those who have previously received anti-C5 therapy. The main objective of this review was to elucidate the clinical efficacy and safety of the newly approved factor B inhibitor, iptacopan. Iptacopan plays a proximal role in the alternative complement pathway to control extravascular hemolysis mediated by C3b and intravascular hemolysis mediated by terminal complement. The recommended dosage is 200 mg orally twice daily. The 24-week results of the pivotal phase III open-label trial, APPLY-PNH, demonstrated that among PNH patients who had previously received anti-C5 therapy, 51/60 (estimated percentages 82%) of patients in the iptacopan group showed an increase in hemoglobin of ≥2 g/dL compared to 0/35 (estimated percentages 2%) in the standard treatment group, also, 69% of iptacopan-treated patients achieved hemoglobin levels ≥12 g/dL, while no patients in the standard treatment group reached this level (both p < 0.001). The 48-week results were similar to those observed at 24 weeks. The most common adverse events were headache, infection and diarrhea. There were almost no clinical breakthrough hemolysis. Trials evaluating the long-term safety and efficacy of iptacopan are currently recruiting.

Degradation of petroleum hydrocarbon contaminants by Rhodococcus erythropolis KB1 synergistic with alfalfa (Medicago sativa L.).

Petroleum hydrocarbons are a stubborn pollutant that is difficult to degrade globally, and plant-microbial degradation is the main way to solve this type of pollutant. In this study, the physiological and ecological responses of alfalfa to petroleum hydrocarbons in different concentrations of petroleum hydrocarbon-contaminated soil with KB1 (Rhodococcus erythropolis) were analyzed and determined by laboratory potting techniques. The growth of alfalfa (CK) and alfalfa with KB1 (JZ) in different concentrations of petroleum hydrocarbons contaminated soil was compared and analyzed. The results of the CK group showed that petroleum hydrocarbons could significantly affect the activity of alfalfa antioxidant enzyme system, inhibit the development of alfalfa roots and the normal growth of plants, especially in the high-concentration group. KB1 strain had the ability to produce IAA, form biofilm, fix nitrogen, produce betaine and ACC deaminase, and the addition of KB1 could improve the growth traits of alfalfa in the soil contaminated with different concentrations of petroleum hydrocarbons, the content of soluble sugars in roots, and the stress resistance and antioxidant enzyme activities of alfalfa. In addition, the degradation kinetics of the strain showed that the degradation rate of petroleum could reach 75.2% after soaking with KB1. Furthermore, KB1 can efficiently degrade petroleum hydrocarbons in advance and significantly alleviate the damage of high concentration of petroleum hydrocarbons to plant roots. The results showed that KB1 strains and alfalfa plants could effectively enhance the degradation of petroleum hydrocarbons, which provided new ideas for improving bioremediation strategies.

Quinoline Derivatives in Discovery and Development of Pesticides.

Finding highly active molecular scaffold structures is always the key research content of new pesticide discovery. In the research and development of new pesticides, the discovery of new agricultural molecular scaffold structures and new targets still faces great challenges. In recent years, quinoline derivatives have developed rapidly in the discovery of new agriculturally active molecules, especially in the discovery of fungicides. The unique quinoline scaffold has many advantages in the discovery of new pesticides and can provide innovative and feasible solutions for the discovery of new pesticides. Therefore, we reviewed the use of quinoline derivatives and their analogues as molecular scaffolds in the discovery of new pesticides since 2000. We systematically summarized the agricultural biological activity of quinoline compounds and discussed the structure-activity relationship (SAR), physiological and biochemical properties, and mechanism of action of the active compounds, hoping to provide ideas and inspiration for the discovery of new pesticides.

Flexible ureteroscopic treatment of kidney stones: How do the new laser systems change our concepts?

Objective: Flexible ureteroscopy (fURS) has become a widely accepted and effective technique for treating kidney stones. With the development of new laser systems, the fURS approach has evolved significantly. This literature review aims to examine the current state of knowledge on fURS treatment of kidney stones, with a particular focus on the impact of the latest laser technologies on clinical outcomes and patient safety. Methods: We conducted a search of the PubMed/PMC, Web of Science Core Collection, Scopus, Embase (Ovid), and Cochrane Databases for all randomized controlled trial articles on laser lithotripsy in September 2023 without time restriction. Results: We found a total of 22 relevant pieces of literature. Holmium laser has been used for intracavitary laser lithotripsy for nearly 30 years and has become the golden standard for the treatment of urinary stones. However, the existing holmium laser cannot completely powder the stone, and the retropulsion of the stone after the laser emission and the thermal damage to the tissue have caused many problems for clinicians. The introduction of thulium fiber laser and Moses technology brings highly efficient dusting lithotripsy effect through laser innovation, limiting pulse energy and broadening pulse frequency. Conclusion: While the holmium:yttrium-aluminum-garnet laser remains the primary choice for endoscopic laser lithotripsy, recent technological advancements hint at a potential new gold standard. Parameter range, retropulsion effect, laser fiber adaptability, and overall system performance demand comprehensive attention. The ablation efficacy of high-pulse-frequency devices relies on precise targeting, which may pose practical challenges.

A clinical study on gastric cancer patients administered EN and PN versus PN alone in enhanced recovery after surgery.

Background and objectives: Enhanced recovery after surgery (ERAS) recommends avoiding enteral nutrition (EN) due to undesirable sequelae such as pulmonary aspiration and infections. Not using of EN in nongastric resections under ERAS pathways is often successful. However, parenteral nutrition (PN) alone followed by early postoperative oral feeding in gastric cancer patients, recommended by the ERAS guidelines, has unclear benefit and is only adopted after gastric resection. This study aimed to compute the postoperative outcomes of EN and PN compared to those of the ERAS-recommended nutritional pathway. Our secondary objective was to compare postoperative complications between the two groups. Materials and methods: Of 173 gastrectomy patients, 116 patients were in the combined group (EN and PN), whereas 57 patients were in the PN alone group. Statistical analysis was performed with the Statistical Package for the Social Sciences (SPSS) version 26.0.0 software. The data were analyzed by one-way ANOVA, the independent sample t-test, or, in the case of several independent samples, by the Kruskal-Wallis test. Categorical data were analyzed by Pearson's χ2 test or Fisher's exact test. Results: The observed indices included C-reactive protein (CRP), platelet (PLT), white blood cells (WBC), hemoglobin (Hb), albumin, and PRE-albumin. The secondary outcomes included length of hospital stay (LOS), cost, incidence of pulmonary infection, and total incidence of infection. Conclusion: The combined mode of nutrition is feasible and is not associated with postoperative complications in gastric cancer patients under ERAS.

Discovery and Mechanism of a Nematicide Candidate (W3): A Novel Amide Compound Containing a Cyclopropyl Moiety.

To find novel nematicides, we screened the nematicidal activity of compounds in our laboratory compound library. Interestingly, the compound N-((1R,2R)-2-(2-fluoro-4-(trifluoromethyl)phenyl)cyclopropyl)-2-(trifluoromethyl)benzamide (W3) showed a broad spectrum and excellent nematicidal activity. The LC50 values of compound W3 against second-stage juveniles of Bursaphelenchus xylophilus (B. xylophilus), Aphelenchoides besseyi, and Ditylenchus destructor are 1.30, 1.63, and 0.72 mg/L, respectively. Nematicidal activities of compound W3 against second-stage juveniles of Meloidogyne incognita were 87.66% at 100 mg/L. Meanwhile, compound W3 can not only observably inhibit the feeding, reproduction, and egg hatching of B. xylophilus but can also effectively promote the oxidative stress adverse reactions of nematodes and cause intestinal damage. Compound W3 can promote the production of MDA and inhibit the activities of defense enzymes SOD and GST in B. xylophilus. Compound W3 can affect the transcription of genes involved in regulating the tricarboxylic acid cycle in nematodes, resulting in weakened nematode respiration and reduced nematode activity and even death. In addition, compound W3 had good inhibitory activity against five pathogenic fungi. Among them, the EC50 of compound W3 against Fusarium graminearum was 8.4 mg/L. In the future, we will devote ourselves to the toxicological and structural optimization research of the candidate nematicide W3.

Effects of the enhanced recovery after surgery (ERAS) protocol on the postoperative stress state and short-term complications in elderly patients with colorectal cancer.

OBJECTIVE: The aim of this study was to evaluate the feasibility and necessity of enhanced recovery after surgery in elderly patients with colorectal cancer by observing inflammatory markers and postoperative complications. METHODS: Hospitalized colorectal cancer patients from the Affiliated Hospital of Jiangsu University from January 2021 to September 2022 were included in the study and divided into two groups: Enhanced Recovery After Surgery (ERAS) and non-ERAS. Data on postoperative inflammatory markers and complications were also collected. RESULTS: A total of 313 patients with colorectal cancer were included: 182 in the ERAS group and 131 in the non-ERAS group. The patients in the ERAS group had significantly shorter days of postoperative hospitalization, urinary catheter and drainage tube withdrawal times, and recovery of bowel function (P < .05) than those of the non-ERAS group. Moreover, the ERAS group had lower hospitalization expenses than those of the non-ERAS group (P < .05). However, the procalcitonin and tumor necrosis factor (TNF)-α levels in the ERAS group was significantly lower than those in the non-ERAS group on postoperative days 1 and 3 (P < .05), and the interleukin (IL)-6 and IL-10 levels in the ERAS group were significantly lower than those in the non-ERAS group on the 1st, 3rd, and 5th postoperative days (P < .05). The C-reactive protein (CRP) and white blood cell (WBC) levels in the ERAS group were lower than those in the non-ERAS group on postoperative days 3 and 5 (P < .05). However, the hemoglobin levels did not differ significantly (P > .05). The albumin levels did not differ significantly between the two groups before surgery (P > .05); however, the albumin level in the ERAS group was higher than that in the non-ERAS group on postoperative days 3 and 5 (P < .05). The ERAS patients had lower albumin levels after surgery than those of the non-ERAS patients (P < .05). CONCLUSION: ERAS leads to a series of perioperative optimization measures, thereby reducing the postoperative stress response in elderly patients with colorectal cancer and the occurrence of perioperative complications.

Neurophysiological characterization of stroke recovery: A longitudinal TMS and EEG study.

AIMS: Understanding the neural mechanisms underlying stroke recovery is critical to determine effective interventions for stroke rehabilitation. This study aims to systematically explore how recovery mechanisms post-stroke differ between individuals with different levels of functional integrity of the ipsilesional corticomotor pathway and motor function. METHODS: Eighty-one stroke survivors and 15 age-matched healthy adults participated in this study. We used transcranial magnetic stimulation (TMS), electroencephalography (EEG), and concurrent TMS-EEG to investigate longitudinal neurophysiological changes post-stroke, and their relationship with behavioral changes. Subgroup analysis was performed based on the presence of paretic motor evoked potentials and motor function. RESULTS: Functional connectivity was increased dramatically in low-functioning individuals without elicitable motor evoked potentials (MEPs), which showed a positive effect on motor recovery. Functional connectivity was increased gradually in higher-functioning individuals without elicitable MEP during stroke recovery and influence from the contralesional hemisphere played a key role in motor recovery. In individuals with elicitable MEPs, negative correlations between interhemispheric functional connectivity and motor function suggest that the influence from the contralesional hemisphere may be detrimental to motor recovery. CONCLUSION: Our results demonstrate prominent clinical implications for individualized stroke rehabilitation based on both functional integrity of the ipsilesional corticomotor pathway and motor function.

Metal ureteral stents for ureteral stricture: 2 years of experience with 246 cases.

BACKGROUND: Metal ureteral stents (MUS) has gained popularity as an endoscopic treatment alternative for the management of ureteral strictures. The aim of this study was to evaluate the safety, efficacy, and tolerability of MUS for treating ureteral strictures and to identify any factors that could influence the success of this intervention. METHODS: This study is a prospective analysis of the efficacy and safety of MUS for treating ureteral strictures in a single-center setting. The study enrolled 246 patients who had been diagnosed with ureteral strictures and had undergone MUS placement between January 2019 and July 2021. The patients were followed-up for a duration of 2 years. RESULTS: The overall success rate of MUS placement was 71.7%. Furthermore, the success rate of ureteral strictures after kidney transplantation (78.2%) was significantly higher than common ureteral strictures (73.0%) or recurrent ureteral strictures (67.6%). Additionally, postsurgery, there was a considerable reduction in hydronephrosis volume (68.9±96.1 vs. 32.1±48.8 cm 3 ), blood creatinine level (103.7±49.8 vs. 94.4±47.5 mol/l) and urea nitrogen level (6.7±7.2 vs. 5.1±2.4 mmol/l). The study also reported that the rate of adverse events associated with MUS was relatively low, included hematuria (7.9%), pain (6.8%), urinary tract infection (6.4%), and lower urinary tract symptoms (5.3%). CONCLUSIONS: MUS appear to be a safe and effective treatment option for ureteral strictures, with a high success rate and low complication rate. These results have important implications for the management of ureteral strictures and can help guide clinical decision-making in the selection of treatment options.

MT4MTL-KD: A Multi-Teacher Knowledge Distillation Framework for Triplet Recognition.

The recognition of surgical triplets plays a critical role in the practical application of surgical videos. It involves the sub-tasks of recognizing instruments, verbs, and targets, while establishing precise associations between them. Existing methods face two significant challenges in triplet recognition: 1) the imbalanced class distribution of surgical triplets may lead to spurious task association learning, and 2) the feature extractors cannot reconcile local and global context modeling. To overcome these challenges, this paper presents a novel multi-teacher knowledge distillation framework for multi-task triplet learning, known as MT4MTL-KD. MT4MTL-KD leverages teacher models trained on less imbalanced sub-tasks to assist multi-task student learning for triplet recognition. Moreover, we adopt different categories of backbones for the teacher and student models, facilitating the integration of local and global context modeling. To further align the semantic knowledge between the triplet task and its sub-tasks, we propose a novel feature attention module (FAM). This module utilizes attention mechanisms to assign multi-task features to specific sub-tasks. We evaluate the performance of MT4MTL-KD on both the 5-fold cross-validation and the CholecTriplet challenge splits of the CholecT45 dataset. The experimental results consistently demonstrate the superiority of our framework over state-of-the-art methods, achieving significant improvements of up to 6.4% on the cross-validation split.

Design, Synthesis, Nematicidal Activity, and Mechanism of Novel Amide Derivatives Containing an 1,2,4-Oxadiazole Moiety.

To discover new nematicides, a series of novel amide derivatives containing 1,2,4-oxadiazole were designed and synthesized. Several compounds showed excellent nematicidal activity. The LC50 values of compounds A7, A18, and A20-A22 against pine wood nematode (Bursaphelenchus xylophilus), rice stem nematode (Aphelenchoides besseyi), and sweet potato stem nematode (Ditylenchus destructor) were 1.39-3.09 mg/L, which were significantly better than the control nematicide tioxazafen (106, 49.0, and 75.0 mg/L, respectively). Compound A7 had an outstanding inhibitory effect on nematode feeding, reproductive ability, and egg hatching. Compound A7 effectively promoted the oxidative stress of nematodes and caused intestinal damage to nematodes. Compound A7 significantly inhibited the activity of succinate dehydrogenase (SDH) in nematodes, leading to blockage of electron transfer in the respiratory chain and thereby hindering the synthesis of adenosine triphosphate (ATP), which consequently affects the entire oxidative phosphorylation process to finally cause nematode death. Therefore, compound A7 can be used as a potential SDH inhibitor in nematicide applications.

An injectable signal-amplifying device elicits a specific immune response against malignant glioblastoma.

Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.

Synergistic effect of cryptotanshinone and temozolomide treatment against human glioblastoma cells.

Glioblastoma multiforme (GBM) is a complex disease to treat owing to its profound chemoresistance. Therefore, we evaluated the combined effect and therapeutic efficacy of temozolomide (TMZ), a potent alkylating agent and the current gold standard therapy for GBM, and cryptotanshinone (CTS), which inhibits glioma cell proliferation in GBM cells. Using LN229 and U87-MG human GBM cells in a short-term stimulation in vitro model, the cytotoxic and anti-proliferative effects of single and combined treatment with 4 µM CTS and 200 µM TMZ were investigated. Furthermore, cell viability, DNA damage, apoptosis rate, and signal transducer and activator of transcription 3 (STAT3) protein were measured using cytotoxic assay, comet assay, flow cytometry, and western blotting analysis, respectively. The two drugs' synergistic interaction was validated using the synergy score. We found that the anti-proliferative effects of combination therapy using the two drugs were greater than that of each agent used alone (CTS or TMZ). Western blot analysis indicated that treatment of GBM cells with CTS combined with TMZ more significantly decreased the expression of MGMT and STAT3, than that with TMZ alone. Combined treatment with CTS and TMZ might be an effective option to overcome the chemoresistance of GBM cells in a long-term treatment strategy.

Formamide Electrosynthesis from Methanol and Ammonia in Water over Pr-Doped MnO2.

A rare earth element doping strategy is reported to boost the activity and enhance the stability of MnO2 for selective formamide production through electrocatalytic oxidation coupling (EOC) of methanol and ammonia. MnO2 doped with 1% Pr was selected as the best candidate with an optimized formamide yield of 211.32 µmol cm-2 h-1, a Faradaic efficiency of 22.63%, and a stability of more than 50 h. The easier formation of Mn6+ species and the lower dissolution rate of Mn species over Pr-doped MnO2 revealed by in situ Raman spectra were responsible for the boosted formamide production and enhanced stability. In addition, a two-electrode flow electrolyzer was developed to integrate EOC with C2H2 semihydrogenation for simultaneously producing value-added products in both the anode and cathode.

The effectiveness of intermittent theta burst stimulation for upper limb motor recovery after stroke: a systematic review and meta-analysis of randomized controlled trials.

Background: Intermittent theta burst stimulation (iTBS) is a promising noninvasive therapy to restore the excitability of the cortex, and subsequently improve the function of the upper extremities. Several studies have demonstrated the effectiveness of iTBS in restoring upper limb function and modulating cortical excitability. We aimed to evaluate the effects of iTBS on upper limb motor recovery after stroke. Objective: The purpose of this article is to evaluate the influence of intermittent theta-burst stimulation on upper limb motor recovery and improve the quality of life. Method: A literature search was conducted using PubMed, EMBASE, MEDLINE, The Cochrane Library, Web of Science, and CBM, including only English studies, to identify studies that investigated the effects of iTBS on upper limb recovery, compared with sham iTBS used in control groups. Effect size was reported as standardized mean difference (SMD) or weighted mean difference (WMD). Results: Ten studies were included in the meta-analysis. The results of the meta-analysis indicated that when compared to the control group, the iTBS group had a significant difference in the Fugl-Meyer Assessment (FMA) and Action Research Arm Test (ARAT) (WMD: 3.20, 95% CI: 1.42 to 4.97; WMD: 3.72, 95% CI: 2.13 to 5.30, respectively). In addition, there was also a significant improvement in the modified Ashworth scale (MAS) compared to the sham group (WMD: -0.56; 95% CI: -0.85 to -0.28). More evidence is still needed to confirm the effect of Barthel Index (BI) scores after interventions. However, no significant effect was found for the assessment of Motor Evoked Potential (MEP) amplitude and MEP latency (SMD: 0.35; 95% CI: -0.21 to 0.90; SMD: 0.35, 95% CI: -0.18 to 0.87; SMD: 0.03, 95% CI: -0.49 to 0.55; respectively). Conclusion: Our results showed that iTBS significantly improved motor impairment, functional activities, and reduced muscle tone of upper limbs, thereby increasing the ability to perform Activities of Daily Living (ADL) in stroke patients, while there were no significant differences in MEPs. In conclusion, iTBS is a promising non-invasive brain stimulation as an adjunct to therapy and enhances the therapeutic effect of conventional physical therapy. In the future, more randomized controlled trials with large sample sizes, high quality, and follow-up are necessary to explore the neurophysiological effects. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023392739.