rTMS for Poststroke Pusher Syndrome: A Randomized, Patient-Blinded Controlled Clinical Trial.

BACKGROUND: Patients with poststroke pusher syndrome (PS) require longer duration of rehabilitation and more supplemental care after discharge. Effective treatment of PS remains a challenge. The role of repetitive transcranial magnetic stimulation (rTMS) for PS has not been examined. OBJECTIVE: Assess the efficacy of rTMS for patients with poststroke PS in reducing pushing behavior, enhancing motor recovery and improving mobility. METHODS: A randomized, patient- and assessor-blinded sham-controlled trial with intention-to-treat analysis was conducted. Thirty-four eligible patients with poststroke PS were randomly allocated to receive either rTMS or sham rTMS for 2 weeks. Pushing behavior on the Burke lateropulsion scale and scale for contraversive pushing, motor function on Fugl-Meyer assessment scale-motor domain (FMA-m) and mobility on modified Rivermead mobility index were measured at baseline, 1 and 2 weeks after intervention. Repeated-measures analysis of covariance was used for data analysis. RESULTS: There was no significant interaction between intervention and time on Burke lateropulsion scale (F = 2.747, P = .076), scale for contraversive pushing (F = 1.583, P = .214), or change of modified Rivermead mobility index (F = 1.183, P = .297). However, a significant interaction between intervention and time was observed for FMA-m (F = 5.464, P = .019). Post hoc comparisons of FMA-m show better improvement in rTMS group with mean differences of 12.7 (95% CI -7.3 to 32.7) and 15.7 (95% CI -4.6 to 36.0) at post-treatment week 1 and week 2 respectively. CONCLUSIONS: rTMS did not demonstrate significant efficacy in improving pushing behavior and mobility in patients with PS. However, rTMS might have potential effect in enhancing motor function for patients with PS. REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (registration No. ChiCTR2200058015 at http://www.chictr.org.cn/searchprojen.aspx) on March 26, 2022.

The Role of Interprofessional Education in Optimizing Laparoscopic Skills Training: A Randomized Controlled Trial.

Background: This investigation evaluates the utility and benefits of integrating interprofessional education (IPE) into laparoscopic training, aiming to enrich medical education and skill acquisition methodologies. Methods: The study randomly allocated 36 participants of a 2023 laparoscopic training course into experimental and control groups, each comprising 18 individuals. The control group underwent traditional theory and practical training, whereas the experimental group additionally engaged in interdisciplinary instruction with nursing educators and participated in simulated laparoscopic surgery exercises. The effectiveness of this interdisciplinary approach was assessed by comparing laparoscopic theory and simulation performance, Objective Structured Assessment of Technical Skills (OSATS) scores in animal-based training, and course satisfaction between the groups. Moreover, the impact on interdisciplinary collaborative competencies was measured through pre- and post-training self-evaluations using the Interprofessional Collaborative Competency Attainment Survey (ICCAS) in the experimental group. Results: The experimental group demonstrated superior performance in laparoscopic theory and simulation, as well as higher OSATS scores, compared with the control group. Satisfaction ratings regarding the skills practice mode, effects, and instructional quality were also significantly better in the experimental group (P < .05, P < .01). Furthermore, participants in the experimental group reported significant pre-to-post training enhancements in interprofessional communication, team collaboration, role perception, conflict management, and learning and feedback marked by statistically significant differences (P < .05, P < .01). Conclusion: The introduction of an IPE framework significantly boosts laparoscopic training efficiency and promotes team collaboration awareness. This model effectively bridges gaps between disciplines, illustrating substantial applicative value and expansion potential within medical education and skill training arenas.

Prediction of Residual Compressive Strength after Impact Based on Acoustic Emission Characteristic Parameters.

This study proposes a prediction method for residual compressive strength after impact based on the extreme gradient boosting model, focusing on composite laminates as the studied material system. Acoustic emission tests were conducted under controlled temperature and humidity conditions to collect characteristic parameters, establishing a mapping relationship between these parameters and residual compressive strength under small sample conditions. The model accurately predicted the residual compressive strength of the laminates after impact, with the coefficient of determination and root mean square error for the test set being 0.9910 and 2.9174, respectively. A comparison of the performance of the artificial neural network model and the extreme gradient boosting model shows that, in the case of small data volumes, the extreme gradient boosting model exhibits superior accuracy and robustness compared to the artificial neural network. Furthermore, the sensitivity of acoustic emission characteristic parameters is analyzed using the SHAP method, revealing that indicators such as peak amplitude, ring count, energy, and peak frequency significantly impact the prediction results of residual compressive strength. The machine-learning-based method for assessing the damage tolerance of composite laminates proposed in this paper utilizes the global monitoring advantages of acoustic emission technology to rapidly predict the residual compressive strength after the impact of composite laminates, providing a theoretical approach for online structural health monitoring of composite laminates. This method is applicable to various composite laminate structures under different impact conditions, demonstrating its broad applicability and reliability.

Single-atom nanozymes: Emerging talent for sensitive detection of heavy metals.

In recent years, the increasingly severe pollution of heavy metals has posed a significant threat to the environment and human safety. Heavy metal ions are highly non-biodegradable, with a tendency to accumulate through biomagnification. Consequently, accurate detection of heavy metal ions is of paramount importance. As a new type of synthetic nanomaterials, single-atom nanozymes (SANs) boast exceptional enzyme-like properties, setting them apart from natural enzymes. This unique feature affords SANs with a multitude of advantages such as dispersed active sites, low cost and variety of synthetic methods over natural enzymes, making them an enticing prospect for various applications in industrial, medical and biological fields. In this paper, we systematically summarize the synthetic methods and catalytic mechanisms of SANs. We also briefly review the analytical methods for heavy metal ions and present an overall overview of the research progress in recent years on the application of SANs in the detection of environmental heavy metal ions. Eventually, we propose the existing challenges and provide a vision for the future.

Engineering Chimeric Chemoreceptors and Two-Component Systems for Orthogonal and Leakless Biosensing of Extracellular γ-Aminobutyric Acid.

Two-component systems (TCSs) sensing and responding to various stimuli outside and inside cells are valuable resources for developing biosensors with synthetic biology applications. However, the use of TCS-based biosensors suffers from a limited effector spectrum, hypersensitivity, low dynamic range, and unwanted signal crosstalk. Here, we developed a tailor-made Escherichia coli whole-cell γ-aminobutyric acid (GABA) biosensor by engineering a chimeric GABA chemoreceptor PctC and TCS. By testing different TCSs, the chimeric PctC/PhoQ showed the response to GABA. Chimera-directed evolution and introduction of the insulated chimeric pair PctC/PhoQ*PhoP* produced biosensors with up to 3.50-fold dynamic range and good orthogonality. To further enhance the dynamic range and lower the basal leakage, three strategies, engineering of PhoP DNA binding sites, fine-tuning reporter expression by optimizing transcription/translation components, and a tobacco etch virus protease-controlled protein degradation, were integrated. This chimeric biosensor displayed a low basal leakage, a large dynamic range (15.8-fold), and a high threshold level (22.7 g L-1). Finally, the optimized biosensor was successfully applied in the high-throughput microdroplet screening of GABA-overproducing Corynebacterium glutamicum, demonstrating its desired properties for extracellular signal biosensing.

Advances in Polymeric Nanomaterial-mediated Autophagy for Cancer Therapy.

Autophagy is an important biological mechanism for eukaryotic cells to regulate growth, death, and energy metabolism, and plays an important role in removing damaged organelles, misfolded or aggregated proteins, and clearing pathogens. It has been found that autophagy is closely related to cell survival and death, and is of great significance in cancerigenesis and development, playing a bidirectional role in cancer inhibition and cancer promotion. Therefore, treating cancers by regulating autophagy has attracted much attention. A large amount of research evidence indicates that polymeric nanomaterials are able to regulate cellular autophagy, and their good biocompatibility, degradability, and functionalizable modification open up a broad application prospect for improving the therapeutic effect of cancers. This review provides an overview of the research progress of polymeric nanomaterials for modulating autophagy in the treatment of cancers.

ß-Hydroxybutyrate Protects Against Cisplatin-Induced Renal Damage via Regulating Ferroptosis.

Cisplatin is a particularly potent antineoplastic drug. However, its usefulness is restricted due to the induction of nephrotoxicity. More recent research has indicated that ß-hydroxybutyrate (ß-HB) protects against acute or chronic organ damage as an efficient healing agent. Nonetheless, the therapeutic mechanisms of ß-HB in acute kidney damage caused by chemotherapeutic drugs remain unclear. Our study developed a model of cisplatin-induced acute kidney injury (AKI), which involved the administration of a ketogenic diet or ß-HB. We analyzed blood urea nitrogen (BUN) and creatinine (Cr) levels in serum, and used western blotting and immunohistochemical staining to assess ferroptosis and the calcium/calmodulin-dependent kinase kinase 2 (Camkk2)/AMPK pathway. The mitochondrial morphology and function were examined. Additionally, we conducted in vivo and in vitro experiments using selective Camkk2 inhibitor or activator to investigate the protective mechanism of ß-HB on cisplatin-induced AKI. Exogenous or endogenous ß-HB effectively alleviated cisplatin-induced abnormally elevated levels of BUN and Cr and renal tubular necrosis in vivo. Additionally, ß-HB reduced ferroptosis biomarkers and increased the levels of anti-ferroptosis biomarkers in the kidney. ß-HB also improved mitochondrial morphology and function. Moreover, ß-HB significantly attenuated cisplatin-induced cell ferroptosis and damage in vitro. Furthermore, western blotting and immunohistochemical staining indicated that ß-HB may prevent kidney injury by regulating the Camkk2-AMPK pathway. The use of the Camkk2 inhibitor or activator verified the involvement of Camkk2 in the renal protection by ß-HB. This study provided evidence of the protective effects of ß-HB against cisplatin-induced nephrotoxicity and identified inhibited ferroptosis and Camkk2 as potential molecular mechanisms.

ß-HB protects against cisplatin-induced renal damage both in vivo and in vitro.Moreover, ß-HB is effective in attenuating cisplatin-induced lipid peroxidation and ferroptosis.The regulation of energy metabolism, as well as the treatment involving ß-HB, is associated with Camkk2.

L-DOPA ameliorates hippocampus-based mitochondria respiratory dysfunction caused by GCI/R injury.

Mitochondrial dysmorphology/dysfunction follow global cerebral ischemia-reperfusion (GCI/R) injury, leading to neuronal death. Our previous researches demonstrated that Levodopa (L-DOPA) improves learning and memory impairment in GCI/R rats by increasing synaptic plasticity of hippocampal neurons. This study investigates if L-DOPA, used in Parkinson's disease treatment, alleviates GCI/R-induced cell death by enhancing mitochondrial quality. Metabolomics and transcriptomic results showed that GCI/R damage affected the Tricarboxylic acid (TCA) cycle in the hippocampus. The results of this study show that L-DOPA stabilized mitochondrial membrane potential and ultrastructure in hippocampus of GCI/R rats, increased dopamine level in hippocampus, decreased succinic acid level, and stabilized Ca2+ level in CA1 subregion of hippocampus. As a precursor of dopamine, L-DOPA is presumed to improves mitochondrial function in hippocampus of GCI/R rats. However, dopamine cannot cross the blood-brain barrier, so L-DOPA is used in clinical therapy to supplement dopamine. In this investigation, OGD/R models were established in isolated mouse hippocampal neurons (HT22) and primary rat hippocampal neurons. Notably, dopamine exhibited a multifaceted impact, demonstrating inhibition of mitochondrial reactive oxygen species (mitoROS) production, stabilization of mitochondrial membrane potential and Ca2+ level, facilitation of TCA circulation, promotion of aerobic respiratory metabolism, and downregulation of succinic acid-related gene expression. Consistency between in vitro and in vivo results underscores dopamine's significant neuroprotective role in mitigating mitochondrial dysfunction following global cerebral hypoxia and ischemia injury. Supplement dopamine may represent a promising therapy to the cognitive impairment caused by GCI/R injury.

Study on the thermal behaviour of spontaneous combustion of open-pit minerals.

To study thermal behaviour during spontaneous combustion of an open-pit coal mine, mixed slag (coal, oil shale, and coal gangue) was taken as the research object. Laser thermal conductivity analyser and differential scanning calorimetry were used to test thermophysical parameters and heat release characteristics of the minerals. The parameters can be employed to calculate the apparent activation energy using the Arrhenius equation and evaluate the thermal behaviour of open-pit mixed slag. The results indicate that thermophysical parameters have stage characteristics. Thermal diffusivity and thermal conductivity of minerals, especially mixed slag, have a strong correlation with temperature. Heat flow of minerals exhibits five characteristic stages, and heat flow of the samples is consistent with the change in heating rate. During the heating process, thermal diffusivity and heat flow of the mixed slag are between those of a single mineral. Except for the mixed slag at 15 and 20 °C/min, the initial exothermic temperature of the other samples is mainly concentrated at 50-80 °C. Thermal energy release of the sample is mainly concentrated in the accelerated exothermic stage and rapid exothermic stage. Thermal energy release of mixed slag in rapid exothermic stage is always greater than that in accelerated exothermic stage, and the proportion of thermal energy release in these two stages exceeds 98 %. The apparent activation energy during the accelerated exothermic stage is lower, making it easier to release heat, and rapid exothermic stage is relatively high, which can readily lead to heat accumulation. Thermal analysis reveals that the thermal behaviour of mixed slag is significantly different from that of a single mineral. Its unique exothermic characteristics can provide a more accurate theoretical basis for the prevention and control of environmental pollution caused by slag spontaneous combustion.

NCAPD3 is a prognostic biomarker and is correlated with immune infiltrates in glioma.

Non-SMC Condensin II Complex Subunit D3 (NCAPD3) has been linked with the genesis and progression of multiple human cancers. Nevertheless, the scientific value and molecular process of NCAPD3 in glioma remain unclear. We explored the level of NCAPD3 expression in pan-cancer by multiple online databases. And we focused on the level and prognostic value of NCAPD3 expression in glioma by immunohistochemistry (IHC) and survival analysis. Meanwhile, we verified the relationship between NCAPD3, biological function and immune infiltration in glioma by Linkedomics and SangerBox databases. The expression of NCAPD3 was increased in a variety of cancers, including glioma. Its high expression was strongly related to WHO grade (P=0.002) and programmed cell death ligand 1 (PD-L1) expression of glioma (P=0.001). Patients with a high level of NCAPD3 expression had a lower overall survival (OS) in glioma than patients with a low level of NCAPD3 expression. Multivariate statistical analyses showed NCAPD3 expression (P=0.040), WHO grade (P<0.001), 1p/19q codeletion (P<0.001), recurrence (P<0.001), age (P=0.023), and chemotherapy status (P=0.001) were meaningful independent prognostic factors in patients with glioma. Furthermore, bioinformatics analysis proved that NCAPD3 has been linked to immune infiltration in glioma. High level of NCAPD3 expression may serve as a promising prognostic biomarker and correlate with dendritic cell infiltration, representing a potential immunotherapy target in glioma.

Flexible TAM requirement of TnpB enables efficient single-nucleotide editing with expanded targeting scope.

TnpBs encoded by the IS200/IS605 family transposon are among the most abundant prokaryotic proteins from which type V CRISPR-Cas nucleases may have evolved. Since bacterial TnpBs can be programmed for RNA-guided dsDNA cleavage in the presence of a transposon-adjacent motif (TAM), these nucleases hold immense promise for genome editing. However, the activity and targeting specificity of TnpB in homology-directed gene editing remain unknown. Here we report that a thermophilic archaeal TnpB enables efficient gene editing in the natural host. Interestingly, the TnpB has different TAM requirements for eliciting cell death and for facilitating gene editing. By systematically characterizing TAM variants, we reveal that the TnpB recognizes a broad range of TAM sequences for gene editing including those that do not elicit apparent cell death. Importantly, TnpB shows a very high targeting specificity on targets flanked by a weak TAM. Taking advantage of this feature, we successfully leverage TnpB for efficient single-nucleotide editing with templated repair. The use of different weak TAM sequences not only facilitates more flexible gene editing with increased cell survival, but also greatly expands targeting scopes, and this strategy is probably applicable to diverse CRISPR-Cas systems.

Cobalt/Iron Bimetallic Biochar Composites for Lead(II) Adsorption: Mechanism and Remediation Performance.

The performance of nano-zero-valent iron for heavy metal remediation can be enhanced via incorporation into bimetallic carbon composites. However, few economical and green approaches are available for preparing bimetallic composite materials. In this study, novel Co/Fe bimetallic biochar composites (BC@Co/Fe-X, where X = 5 or 10 represents the CoCl2 concentration of 0.05 or 0.1 mol L-1) were prepared for the adsorption of Pb2+. The effect of the concentration of cross-linked metal ions on Pb2+ adsorption was investigated, with the composite prepared using 0.05 mol L-1 Co2+ (BC@Co/Fe-5) exhibiting the highest adsorption performance. Various factors, including the adsorption period, Pb2+ concentration, and pH, affected the adsorption of Pb2+ by BC@Co/Fe-5. Further characterisation of BC@Co/Fe-5 before and after Pb2+ adsorption using methods such as X-ray diffraction and X-ray photoelectron spectroscopy suggested that the Pb2+ adsorption mechanism involved (i) Pb2+ reduction to Pb0 by Co/Fe, (ii) Co/Fe corrosion to generate Fe2+ and fix Pb2+ in the form of PbO, and (iii) Pb2+ adsorption by Co/Fe biochar. Notably, BC@Co/Fe-5 exhibited excellent remediation performance in simulated Pb2+-contaminated water and soil with good recyclability.

The chemokine CCL20 can assist AFP in serological diagnosis of hepatocellular carcinoma.

The chemokine 20 (CCL20) is a member of the CC chemokine family and plays a role in tumor immunity and autoimmune disease. This work investigated the value of CCL20 as a serum diagnostic marker for primary hepatocellular carcinoma (HCC). Based on the data of hepatocellular carcinoma patients in the TCGA database, the up-regulated genes encoding secretory proteins were analyzed in each pathological stage, and the candidate marker CCL20 gene was selected. Serum concentrations of CCL20 in patients with primary HCC, benign liver disease, and healthy subjects were analyzed by enzyme-linked immunosorbent assay (ELISA). The ROC curve evaluated the efficacy of CCL20 alone or in combination with AFP in the diagnosis of HCC. It was found the expression of CCL20 in HCC patients was significantly higher than that in the benign liver disease group and healthy controls (P < 0.05); The AUC of ROC curve to distinguish HCC patients from healthy controls was 0.859, the sensitivity was 73.42%, and the specificity was 86.84%. After combination with AFP, the AUC increased to 0.968, the sensitivity was 88.16%, and the specificity was 97.37%. Although CCL20 was increased in the serum of patients with benign liver diseases, combined with AFP, the AUC to distinguish HCC patients from non-HCC cohorts (benign liver disease group and healthy control group) was 0.902, with a sensitivity of 91.67% and a specificity of 75.26%. Collectively, serum CCL20 is closely related to the occurrence of HCC, and detection of serum CCL20 can assist AFP in improving the diagnostic sensitivity of HCC.

Utility, benefits, and risks of newborn genetic screening carrier reports for families.

Background: Newborn genetic screening (NBGS) based on next-generation sequencing offers enhanced disease detection and better detection rates than traditional newborn screening. However, challenges remain, especially around reporting the NBGS carrier results. Therefore, we aimed to investigate the NBGS carrier parents' views on NBGS and NBGS reports in China. Methods: We distributed a survey querying demographic information, knowledge and perceptions of NBGS, the impact of NBGS on a total of 2930 parents, and their decision-making to parents of newborns reported as carriers in NBGS in Nanjing, China in 2022. Results: The average age of the survey respondents was 30.7 years (standard deviation = 3.6). Most (68.38%) felt informed about NBGS, especially women, the highly educated, and high earners. Nearly all (98.74%) saw NBGS as crucial for early disease detection, with 73.18% believing it positively impacts their future. However, 19.16% felt it might cause anxiety, especially among the less educated. Concerns included potential discrimination due to exposed genetic data and strained family ties. Many suggested NBGS coverage by medical insurance to ease financial burdens. Conclusions: Through our study, we gained insights into parents' perspectives and concerns regarding the NBGS carrier result reporting, thus providing relevant information for further refinement and clinical promotion of the NBGS project.

Advances in the Application of Transition-Metal Composite Nanozymes in the Field of Biomedicine.

Due to the limitation that natural peroxidase enzymes can only function in relatively mild environments, nanozymes have expanded the application of enzymology in the biological field by dint of their ability to maintain catalytic oxidative activity in relatively harsh environments. At the same time, the development of new and highly efficient composite nanozymes has been a challenge due to the limitations of monometallic particles in applications and the inherently poor enzyme-mimetic activity of composite nanozymes. The inherent enzyme-mimicking activity is due to Au, Ag, and Pt, along with other transition metals. Moreover, the nanomaterials exhibit excellent enzyme-mimicking activity when composited with other materials. Therefore, this paper focuses on composite nanozymes with simulated peroxidase activity that have been prepared using noble metals such as Au, Ag, and Pt and other transition metal nanoparticles in recent years. Their simulated enzymatic activity is utilized for biomedical applications such as glucose detection, cancer cell detection and tumor treatment, and antibacterial applications.

Brucea javanica derived exosome-like nanovesicles deliver miRNAs for cancer therapy.

Triple-negative breast cancer (TNBC) is characterized by complex heterogeneity, high recurrence and metastasis rates, and short overall survival, owing to the lack of endocrine and targeted receptors, which necessitates chemotherapy as the major treatment regimen. Exosome-like nanovesicles derived from medicinal plants have shown great potential as novel biotherapeutics for cancer therapy by delivering their incorporated nucleic acids, especially microRNAs (miRNAs), to mammalian cells. In this study, we isolated exosome-like nanovesicles derived from B. javanica (BF-Exos) and investigated their influence and underlying molecular mechanisms in TNBC. We found that BF-Exos delivered 10 functional miRNAs to 4T1 cells, significantly retarding the growth and metastasis of 4T1 cells by regulating the PI3K/Akt/mTOR signaling pathway and promoting ROS/caspase-mediated apoptosis. Moreover, BF-Exos were shown to inhibit the secretion of vascular endothelial growth factor, contributing to anti-angiogenesis in the tumor microenvironment. In vivo, BF-Exos inhibited tumor growth, metastasis, and angiogenesis in breast tumor mouse models, while maintaining high biosafety. Overall, BF-Exos are considered promising nanoplatforms for the delivery of medicinal plant-derived nucleic acids, with great potential to be developed into novel biotherapeutics for the treatment of TNBC.

Advances in the application of metal oxide nanozymes in tumor detection and treatment.

Natural enzymes play an important role to support the regular life activities of the human body. However, the application conditions of natural enzymes are harsh and there are limitations in their use. As artificial enzymes, nanozymes possess the substrate specificity of natural enzymes. Due to the advantages of low cost, good stability and strong catalytic properties, nanozymes hold a wide range of applications in the fields of sensing, chemical, food and medicine. Some of the more common ones are noble metal nanozymes, metal oxide nanozymes and carbon-based nanozymes. Among them, metal oxide nanozymes have attracted much attention because of their decent fixity, exceedingly good physicochemical properties and other advantages. Today, malignant tumors pose a great danger to the human body and are a serious threat to human health. However, traditional treatments have more side effects, and finding new treatment modalities is particularly important for tumor treatment. For example, enzyme therapy can be used to catalyze reactions in the body to achieve tumor treatment. Nanozymes can exert enzymatic activity and effectively treat malignant tumors through catalysis and synergy, and have made certain progress. This paper reviews the detection and application of metal oxide nanozymes in tumor detection and treatment in recent years and provides an outlook on their future application and development.