Effect of pretreatment with electron beam irradiation on the deacetylation efficiency of konjac glucomannan and its structural, physicochemical and gel properties.

Due to its emulsifying and thickening properties, konjac glucomannan (KGM) is widely used in the food, medicine, and materials industries. Nevertheless, its high viscosity and significant water absorption limit its application range. Therefore, electron beam (e-beam) irradiation pretreatment was carried out to improve the deacetylation efficiency of KGM, and the physicochemical and gel properties of KGM were investigated. The results show that e-beam irradiation and deacetylation decrease the water absorption, solubility, transparency, molecular weight, and viscosity of KGM. Conversely, the moisture content, thermal stability, and water-binding capacity increase. FTIR and X-ray diffraction analysis revealed no significant changes in the chemical and crystalline structure of KGM before and after modification. However, modification weakens the intermolecular interaction of KGM hydrosols, which affects their rheology. Furthermore, deacetylation improves the mechanical properties and water retention capacity of KGM gels. Overall, the e-beam irradiation pretreatment provides a method to increase the efficiency of KGM deacetylation and improve the physical and chemical properties of KGM, thus expanding its potential applications in the food and chemical industries, among others.

[Comparison of Short-term Efficacy of Neoadjuvant Immunotherapy Combined with Chemotherapy and Surgery Alone for Locally Advanced Resectable 
Non-small Cell Lung Cancer].

BACKGROUND: Lung cancer is the cancer with the highest incidence and mortality rates in China, and non-small cell lung cancer (NSCLC) accounts for 80%-85% of all malignant lung tumors. Currently, surgical treatment remains the primary treatment modality for lung cancer. In recent years, the effectiveness of immune checkpoint inhibitors for NSCLC has become a consensus, and neoadjuvant immunochemotherapy (nICT) has shown promising efficacy and safety in early to intermediate stage NSCLC. However, there are fewer studies related to nICT for locally advanced NSCLC. This study aims to evaluate the efficacy and safety of nICT therapy in locally advanced resectable NSCLC. METHODS: 85 confirmed resectable stage IIIA and IIIB patients treated in the Department of Thoracic Surgery, Second Hospital of Lanzhou University, from January 2021 to April 2024, were divided into the nICT group (n=32) and the surgery alone group (n=53). Clinical baseline data, perioperative indicators, postoperative complications, imaging response rate, pathological response rate, incidence of adverse events, and quality of life were compared between the two groups. RESULTS: There were no statistically significant differences in clinical baseline data between the two groups (P>0.05). Incidence of choosing thoracotomy was higher in the nICT group than in the surgery alone group (P=0.002). There were no significant differences in surgical time, intraoperative blood loss, number of dissected lymph nodes, duration of chest tube placement, postoperative hospital stay, and R0 resection rate between the two groups (P>0.05). The overall incidence of postoperative complications was 31.25% in the nICT group and 22.64% in the surgery alone group, with no statistically significant difference (P=0.380). In the nICT group, the objective response rate (ORR) was 84.38%, with 5 cases of complete response (CR)(15.63%), 22 cases of partial response (PR)(68.75%), 15 cases of pathological response rate (pCR)(46.88%), and 11 cases of major pathological reaponse (MPR) (34.38%). During nICT treatment, 12 cases (37.50%) experienced grade 3 treatment-related adverse events, no death induced by adverse events or immune related adverse events. Moreover, the symptoms of the patients were improved after nICT treatment. CONCLUSIONS: Neoadjuvant immunochemotherapy shows promising efficacy in locally advanced resectable NSCLC, with manageable treatment-related adverse events. It is a safe and feasible neoadjuvant treatment modality for locally advanced resectable NSCLC.

Clinical application of LARS tumor tube in joint function reconstruction of tumor type artificial hip replacement. / LARSè‚¿ç˜¤ç®¡åœ¨è‚¿ç˜¤åž‹äººå·¥é«‹å ³èŠ‚ç½®æ¢æœ¯å ³èŠ‚åŠŸèƒ½é‡å»ºä¸­çš„ä¸´åºŠåº”ç”¨.

OBJECTIVES: Proximal femur tumor resection often leads to hip joint instability and functional loss. Various methods have been clinically applied to repair hip joint soft tissue function, but deficiencies remain. This study aims to evaluate the advantages and disadvantages of the ligament advanced reinforcement system (LARS) tumor tube in assisting soft tissue function reconstruction in patients undergoing tumor type artificial hip replacement surgery. METHODS: This study included 85 patients (41 males, 44 females) with proximal femoral tumors treated at the Xiangya Bone Tumor Treatment Center from January 2012 to January 2022, aged 10 to 79 (38.5±18.2) years. Among them, 13 cases had benign aggressive tumors, 45 had primary malignant bone tumors, and 27 had bone metastases. Clinical data, imaging data, and intraoperative photos were collected. Patients were followed up and postoperative functional evaluations were conducted using the Musculoskeletal Tumor Society (MSTS) scoring system and Harris hip joint scoring system to assess limb function and hip joint function. RESULTS: Preoperative pathological fractures were present in 37 cases (43.5%), with a lesion length of (9.4±2.9) cm. Among non-metastatic tumor patients, 7 experienced postoperative recurrence, including 6 cases of osteosarcoma and 1 case of fibrosarcoma. Pulmonary metastases occurred in 9 osteosarcoma patients. Five patients required reoperation due to postoperative complications, including 3 cases of deep vein thrombosis, 1 case of giant cell granuloma, and 1 case of prosthesis infection. Postoperatively, 5 patients exhibited Trendelenburg gait, and 6 had leg length discrepancies. The postoperative MSTS score was 26.7±1.4, and the Harris score was 89.6±5.3. CONCLUSIONS: The LARS tumor tube can effectively assist in reconstructing the soft tissue function of the hip joint and greatly reduce postoperative complications, making it an effective technical improvement in joint function reconstruction in tumor type artificial hip replacement surgery.

A novel inflammatory nutrient index for predicting survival outcomes in patients with non-small cell lung cancer.

Background: Lung cancer is one of the most common contributors to cancer-related deaths worldwide. This study aimed to develop a new blood index on the basis of the patient's systemic inflammation and nutritional status, which can be used to predict the prognosis of patients with non-small cell lung cancer (NSCLC). Methods: Pre-treatment blood markers were analyzed in 556 NSCLC patients from 2010 to 2019. A least absolute shrinkage and selection operator (LASSO) method was used to select indicators to establish a new integrated biomarker (PNAGR). Kaplan-Meier survival curves were used to assess the prognostic impact of platelet-to-lymphocyte ratio (PLR), albumin (ALB), and the PNAGR. The prognostic value was verified using univariate and multivariate Cox analyses. Results: We used four biomarkers including PLR, ALB, 1/albumin-to-globulin ratio (1/AGR), and neutrophil/albumin-to-globulin ratio (N/AGR) were used to screen for the PNAGR using LASSO. Patients with high PNAGR demonstrated lower overall survival (OS) compared to those with low PNAGR. In both univariate and multivariate analyses, PNAGR was revealed as an independent prognostic factor for OS. The predictive power of PNAGR [area under the curve (AUC): 0.753] was higher than that of the metrics alone. Conclusions: PNAGR is a novel and effective clinical prognostic tool with good clinical predictive value for NSCLC patients.

Genomic characteristics of adipose-derived stromal cells induced into neurons based on single-cell RNA sequencing.

Adipose-derived stromal cells (ADSCs) can be induced to differentiate into neurons, representing the most promising avenue for cell therapy. However, the molecular mechanism and genomic characteristics of the differentiation of ADSCs into neurons remain poorly understood. In this study, cells from the adult ADSCs group, induction 1h, 3h, 5h, 6h, and 8h groups were selected for single-cell RNA sequencing (scRNA-Seq). Samples from these seven-time points were sequenced and analyzed. The expression of neuron marker genes, including NES, MAP2, TMEM59L, PTK2B, CHN1, DNM1, NRSN2, FBLN2, SCAMP1, SLC1A1, DLG4, CDK5, and ENO2, was found to be low in the ADSCs group, but highly expressed in differentiated cell clusters. The expression of stem cell marker genes, including CCND1, IL1B, MMP1, MMP3, MYO10, and BMP2, was the highest in the ADSCs cluster. This expression decreased significantly with the extension of induction time. Gene ontology (GO) enrichment analysis of upregulated genes in the induced samples showed that the biological processes related to neuronal differentiation and development, such as neuronal differentiation, projection, and apoptosis, were significantly upregulated with a longer induction time during cell cluster differentiation. The results of the cell communication analysis demonstrated the gradual formation of complex neural network connections between ADSC-derived neurons through receptor and ligand pairs at 5h after the induction of differentiation.

ZmSPL10, ZmSPL14 and ZmSPL26 act together to promote stigmatic papilla formation in maize through regulating auxin signaling and ZmWOX3A expression.

Maize silk is a specialized type of stigma, covered with numerous papillae for pollen grain capture. However, the developmental process of stigmatic papillae and the underlying regulatory mechanisms have remained largely unknown. Here, we combined the cytological, genetic and molecular studies to demonstrate that three homologous genes ZmSPL10, ZmSPL14 and ZmSPL26 play a central role in promoting stigmatic papilla formation in maize. We show that their triple knockout mutants are nearly complete lack of stigmatic papilla, resulting in a severe reduction in kernel setting. Cellular examination reveals that stigmatic papilla is developed from a precursor cell, which is the smaller daughter cell resulting from asymmetric cell division of a silk epidermal cell. In situ hybridization shows that ZmSPL10, ZmSPL14 and their target genes SPI1, ZmPIN1b, ZmARF28 and ZmWOX3A are preferentially expressed in the precursor cells of stigmatic papillae. Moreover, ZmSPL10, ZmSPL14 and ZmSPL26 directly bind to the promoters of SPI1, ZmPIN1b, ZmARF28 and ZmWOX3A and promote their expression. Further, Zmwox3a knockout mutants display severe defects in stigmatic papilla formation and reduced seed setting. Collectively, our results demonstrate that ZmSPL10, ZmSPL14 and ZmSPL26 act together to promote stigmatic papilla development through regulating auxin signaling and ZmWOX3A expression.

Intensive Versus Moderate Statin-Based Therapies in Patients With Mild Ischemic Stroke: A Prospective Multicenter Cohort Study.

BACKGROUND: Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin-based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high-dose and moderate-dose statins for patients who had experienced mild ischemic stroke during the acute period. METHODS AND RESULTS: This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high-intensity and moderate-intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow-up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high-intensity statin and moderate-intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85-1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86-1.34]; P=0.519). High-intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00-3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10-3.16]; P=0.021). The results from the propensity score-matched analyses were consistent with those from the Cox proportional hazards analysis. CONCLUSIONS: Compared with moderate-intensity statin therapy, high-dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. REGISTRATION: URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

RSV Risk Profile in Hospitalized Adults and Comparison with Influenza and COVID-19 Controls in Valladolid, Spain, 2010-2022.

INTRODUCTION: We aimed to describe the risk profile of respiratory syncytial virus (RSV) infections among adults ≥ 60 years in Valladolid from January 2010 to August 2022, and to compare them with influenza and COVID-19 controls. METHODS: This was a retrospective cohort study of all laboratory-confirmed RSV infections identified in centralized microbiology database during a 12-year period. We analyzed risk factors for RSV hospitalization and severity (length of stay, intensive care unit admission, in-hospital death or readmission < 30 days) and compared severity between RSV patients vs. influenza and COVID-19 controls using multivariable logistic regression models. RESULTS: We included 706 RSV patients (635 inpatients and 71 outpatients), and 598 influenza and 60 COVID-19 hospitalized controls with comparable sociodemographic profile. Among RSV patients, 96 (15%) had a subtype identified: 56% A, 42% B, and 2% A + B. Eighty-one percent of RSV patients had cardiovascular conditions, 65% endocrine/metabolic, 46% chronic lung, and 43% immunocompromising conditions. Thirty-six percent were coinfected (vs. 21% influenza and 20% COVID-19; p = < .0001 and 0.01). Ninety-two percent had signs of lower respiratory infection (vs. 85% influenza and 72% COVID-19, p = < .0001) and 27% cardiovascular signs (vs. 20% influenza and 8% COVID-19, p = 0.0031 and 0.0009). Laboratory parameters of anemia, inflammation, and hypoxemia were highest in RSV. Among RSV, being a previous smoker (adjusted OR 2.81 [95% CI 1.01, 7.82]), coinfection (4.34 [2.02, 9.34]), and having cardiovascular (3.79 [2.17, 6.62]), neurologic (2.20 [1.09, 4.46]), or chronic lung (1.93 [1.11, 3.38]) diseases were risks for hospitalization. Being resident in care institutions (1.68 [1.09, 2.61]) or having a coinfection (1.91[1.36, 2.69]) were risks for higher severity, while RSV subtype was not associated with severity. Whereas RSV and influenza patients did not show differences in severity, RSV patients had 68% (38-84%) lower odds of experiencing any severe outcome compared to COVID-19. CONCLUSIONS: RSV especially affects those with comorbidities, coinfections, and living in care institutions. RSV vaccination could have an important public health impact in this population.

Development and validation of a scale to measure the care needs of Crohn's disease patients: a mixed-methods study.

BACKGROUND: Crohn's disease (CD) patients require varying levels of supportive care. In order to facilitate caregivers and nurses in precisely evaluating the caregiving requirements of these patients, we developed the CD-specific Care Needs Scale (CD-CNS). METHODS: This study employed a mixed-methods approach, integrating qualitative and quantitative methodologies. The initial items of the scale were developed through qualitative interviews, Delphi expert consultation, and literature review, while the final items were refined through clinical testing. Qualitative interviews were conducted based on the supportive care needs framework and Maslow's hierarchy of needs, and scale items were constructed through a literature search and qualitative interviews. The initial version of the scale with 45 items was obtained after the items were verified and modified by expert consultation. A total of 250 CD patients admitted to the gastroenterology department of a hospital in China were selected for verification of the initial version of the scale. A self-designed general questionnaire was used to obtain patients' medical history and sociodemographic data, and the Chinese version of the Inflammatory Bowel Disease Questionnaire (IBDQ) was used as the criterion. Exploratory factor analysis (EFA) was performed on the CD-CNS to evaluate the dimensions, factor structure, reliability, criterion validity, and construct validity. RESULTS: EFA identified 5 dimensions and retained 27 items with strong internal consistency reliability (α = 0.940). The Cronbach's α coefficients for each dimension ranged from 0.824 to 0.921. Criterion validity was assessed using Spearman's coefficient, which demonstrated a significant correlation with the IBDQ (P < 0.050). The test-retest reliability for each dimension after two weeks ranged from 0.655 to 0.895. CONCLUSIONS: We developed and validated a new scale that can be used to assess the care needs of CD patients. This new tool can guide the specific supportive care of CD patients. TRIAL REGISTRATION: This study was reviewed and approved by the Ethics Committee of the Second Hospital of Nanjing (2021-LS-ky-022). The study was duly registered and approved online through the Trial Center of the Second Hospital of Nanjing in 2021. Confidentiality was ensured by anonymizing all the data. The entire study process was conducted under the supervision of the Ethics Committee of Nanjing Second Hospital. Informed consent was obtained from the patients, and each patient volunteered and agreed to participate.

Acupuncture modulation of the ACE/Ang II/AT1R and ACE2/Ang(1-7)/MasR pathways in the rostral ventrolateral medulla reduces sympathetic output and prevents cardiac injury caused by SHR hypertension.

Acupuncture can reduce blood pressure, heart rate (HR), and ameliorate cardiac damage by modulating the excitability of the sympathetic nervous system, but the exact mechanism of this effect remains unclear. This study investigated the potential mechanisms of acupuncture in the treatment of cardiac damage in hypertension. Spontaneously hypertensive rats (SHR) were used as the hypertension model with Wistar-Kyoto rats as the control. Manual acupuncture, electroacupuncture, and metoprolol were used as interventions. Systolic and diastolic blood pressure (SBP, DBP) plus HR were monitored with cardiac structure determined using Masson staining. Angiotensin II (Ang II) and norepinephrine in myocardium were detected with ELISA as was Ang(1-7) and gamma aminobutyric acid (GABA) in the rostral ventrolateral medulla (RVLM). Expression of mRNA for collagen type I (Col-I), Col-III, actin α1 (ACTA1), and thrombospondin 4 (THBS4) in myocardium was detected using real-time PCR. Expression of angiotensin converting enzyme (ACE), Ang II, angiotensin II type 1 receptor (AT1R), ACE2, and Mas receptor (MasR) proteins in RVLM was monitored using western blot. After manual acupuncture and electroacupuncture treatment, SHRs showed decreased SBP, DBP and HR, reduced myocardial damage. There was decreased expression of the ACE/Ang II/AT1R axis, and increased expression of the ACE2/Ang(1-7)/MasR axis within the RVLM. GABA levels were increased within the RVLM and norepinephrine levels were decreased in myocardial tissue. Metoprolol was more effective than either manual acupuncture or electroacupuncture. Acupuncture directed against hypertensive cardiac damage may be associated with regulation of ACE/Ang II/AT1R and the ACE2/Ang(1-7)/MasR pathway within the RLVM to reduce cardiac sympathetic excitability.

Reproductive factors, genetic susceptibility and risk of type 2 diabetes: A prospective cohort study.

AIM: To explore the relationships of multiple reproductive factors with type 2 diabetes mellitus (T2DM) risk and the joint effects of reproductive factors and genetic susceptibility. METHODS: We included 262,368 women without prevalent T2DM from the UK biobank. Cox proportional hazards regression models were employed to estimate the relationships of reproductive factors with T2DM risk and the joint effects of reproductive factors and genetic susceptibility. RESULTS: During a mean follow-up of 12.2 years, 8,996 T2DM cases were identified. Early menarche (<12 years, hazard ratio (HR) 1.08 [95 % confidence interval (CI) 1.02;1.13]), late menarche (≥15 years, HR 1.11 [1.04;1.17]), early menopause (<45 years, HR 1.20 [1.12;1.29]), short reproductive lifespan (<30 years, HR 1.25 [1.16;1.35]), hysterectomy (1.31, HR [1.23;1.40]), oophorectomy (HR 1.28 [1.20;1.36]), high parity (≥4, HR 1.25 [1.17;1.34]), early age at first live birth (<20 years, HR 1.23 [1.16;1.31]), miscarriage (HR 1.13 [1.07;1.19]), stillbirth (HR 1.14 [1.03;1.27]), and ever used hormonal replacement therapy (HR 1.19 [1.14;1.24]) were related to a higher T2DM risk, while ever used oral contraceptives (HR 0.93 [0.89;0.98]) was related to a lower T2DM risk. Furthermore, women with reproductive risk factors and high genetic risk had the highest T2DM risk compared to those with low genetic risk and without reproductive risk factors. CONCLUSION: Our findings show that multiple reproductive factors are related to T2DM risk, particularly in women with high genetic risk.

Impaired ATP hydrolysis in blood plasma contributes to age-related neutrophil dysfunction.

BACKGROUND: The function of polymorphonuclear neutrophils (PMNs) decreases with age, which results in infectious and inflammatory complications in older individuals. The underlying causes are not fully understood. ATP release and autocrine stimulation of purinergic receptors help PMNs combat microbial invaders. Excessive extracellular ATP interferes with these mechanisms and promotes inflammatory PMN responses. Here, we studied whether dysregulated purinergic signaling in PMNs contributes to their dysfunction in older individuals. RESULTS: Bacterial infection of C57BL/6 mice resulted in exaggerated PMN activation that was significantly greater in old mice (64 weeks) than in young animals (10 weeks). In contrast to young animals, old mice were unable to prevent the systemic spread of bacteria, resulting in lethal sepsis and significantly greater mortality in old mice than in their younger counterparts. We found that the ATP levels in the plasma of mice increased with age and that, along with the extracellular accumulation of ATP, the PMNs of old mice became increasingly primed. Stimulation of the formyl peptide receptors of those primed PMNs triggered inflammatory responses that were significantly more pronounced in old mice than in young animals. However, bacterial phagocytosis and killing by PMNs of old mice were significantly lower than that of young mice. These age-dependent PMN dysfunctions correlated with a decrease in the enzymatic activity of plasma ATPases that convert extracellular ATP to adenosine. ATPases depend on divalent metal ions, including Ca2+, Mg2+, and Zn2+, and we found that depletion of these ions blocked the hydrolysis of ATP and the formation of adenosine in human blood, resulting in ATP accumulation and dysregulation of PMN functions equivalent to those observed in response to aging. CONCLUSIONS: Our findings suggest that impaired hydrolysis of plasma ATP dysregulates PMN function in older individuals. We conclude that strategies aimed at restoring plasma ATPase activity may offer novel therapeutic opportunities to reduce immune dysfunction, inflammation, and infectious complications in older patients.

Promoter profiles in plasma CfDNA exhibits a potential utility of predicting the efficacy of neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: Gene expression profiles in breast tissue biopsies contain information related to chemotherapy efficacy. The promoter profiles in cell-free DNA (cfDNA) carrying gene expression information of the original tissues may be used to predict the response to neoadjuvant chemotherapy in breast cancer as a non-invasive biomarker. In this study, the feasibility of the promoter profiles in plasma cfDNA was evaluated as a novel clinical model for noninvasively predicting the efficacy of neoadjuvant chemotherapy in breast cancer. METHOD: First of all, global chromatin (5 Mb windows), sub-compartments and promoter profiles in plasma cfDNA samples from 94 patients with breast cancer before neoadjuvant chemotherapy (pCR = 31 vs. non-pCR = 63) were analyzed, and then classifiers were developed for predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Further, the promoter profile changes in sequential cfDNA samples from 30 patients (pCR = 8 vs. non-pCR = 22) during neoadjuvant chemotherapy were analyzed to explore the potential benefits of cfDNA promoter profile changes as a novel potential biomarker for predicting the treatment efficacy. RESULTS: The results showed significantly distinct promoter profile in plasma cfDNA of pCR patients compared with non-pCR patients before neoadjuvant chemotherapy. The classifier based on promoter profiles in a Random Forest model produced the largest area under the curve of 0.980 (95% CI: 0.978-0.983). After neoadjuvant chemotherapy, 332 genes with significantly differential promoter profile changes in sequential cfDNA samples of pCR patients was observed, compared with non-pCR patients, and their functions were closely related to treatment response. CONCLUSION: These results suggest that promoter profiles in plasma cfDNA may be a powerful, non-invasive tool for predicting the efficacy of neoadjuvant chemotherapy breast cancer patients before treatment, and the on-treatment cfDNA promoter profiles have potential benefits for predicting the treatment efficacy.

Prediction and Interpretation Microglia Cytotoxicity by Machine Learning.

Ameliorating microglia-mediated neuroinflammation is a crucial strategy in developing new drugs for neurodegenerative diseases. Plant compounds are an important screening target for the discovery of drugs for the treatment of neurodegenerative diseases. However, due to the spatial complexity of phytochemicals, it becomes particularly important to evaluate the effectiveness of compounds while avoiding the mixing of cytotoxic substances in the early stages of compound screening. Traditional high-throughput screening methods suffer from high cost and low efficiency. A computational model based on machine learning provides a novel avenue for cytotoxicity determination. In this study, a microglia cytotoxicity classifier was developed using a machine learning approach. First, we proposed a data splitting strategy based on the molecule murcko generic scaffold, under this condition, three machine learning approaches were coupled with three kinds of molecular representation methods to construct microglia cytotoxicity classifier, which were then compared and assessed by the predictive accuracy, balanced accuracy, F1-score, and Matthews Correlation Coefficient. Then, the recursive feature elimination integrated with support vector machine (RFE-SVC) dimension reduction method was introduced to molecular fingerprints with high dimensions to further improve the model performance. Among all the microglial cytotoxicity classifiers, the SVM coupled with ECFP4 fingerprint after feature selection (ECFP4-RFE-SVM) obtained the most accurate classification for the test set (ACC of 0.99, BA of 0.99, F1-score of 0.99, MCC of 0.97). Finally, the Shapley additive explanations (SHAP) method was used in interpreting the microglia cytotoxicity classifier and key substructure smart identified as structural alerts. Experimental results show that ECFP4-RFE-SVM have reliable classification capability for microglia cytotoxicity, and SHAP can not only provide a rational explanation for microglia cytotoxicity predictions, but also offer a guideline for subsequent molecular cytotoxicity modifications.

Multi-scale brain attributes contribute to the distribution of diffuse glioma subtypes.

Gliomas are primary brain tumors and are among the most malignant types. Adult-type diffuse gliomas can be classified based on their histological and molecular signatures as IDH-wildtype glioblastoma, IDH-mutant astrocytoma, and IDH-mutant and 1p/19q-codeleted oligodendroglioma. Recent studies have shown that each subtype of glioma has its own specific distribution pattern. However, the mechanisms underlying the specific distributions of glioma subtypes are not entirely clear despite partial explanations such as cell origin. To investigate the impact of multi-scale brain attributes on glioma distribution, we constructed cumulative frequency maps for diffuse glioma subtypes based on T1w structural images and evaluated the spatial correlation between tumor frequency and diverse brain attributes, including postmortem gene expression, functional connectivity metrics, cerebral perfusion, glucose metabolism, and neurotransmitter signaling. Regression models were constructed to evaluate the contribution of these factors to the anatomic distribution of different glioma subtypes. Our findings revealed that the three different subtypes of gliomas had distinct distribution patterns, showing spatial preferences toward different brain environmental attributes. Glioblastomas were especially likely to occur in regions enriched with synapse-related pathways and diverse neurotransmitter receptors. Astrocytomas and oligodendrogliomas preferentially occurred in areas enriched with genes associated with neutrophil-mediated immune responses. The functional network characteristics and neurotransmitter distribution also contributed to oligodendroglioma distribution. Our results suggest that different brain transcriptomic, neurotransmitter, and connectomic attributes are the factors that determine the specific distributions of glioma subtypes. These findings highlight the importance of bridging diverse scales of biological organization when studying neurological dysfunction.

Dynamic memristor for physical reservoir computing.

Reservoir computing (RC) has attracted considerable attention for its efficient handling of temporal signals and lower training costs. As a nonlinear dynamic system, RC can map low-dimensional inputs into high-dimensional spaces and implement classification using a simple linear readout layer. The memristor exhibits complex dynamic characteristics due to its internal physical processes, which renders them an ideal choice for the implementation of physical reservoir computing (PRC) systems. This review focuses on PRC systems based on memristors, explaining the resistive switching mechanism at the device level and emphasizing the tunability of their dynamic behavior. The development of memristor-based reservoir computing systems is highlighted, along with discussions on the challenges faced by this field and potential future research directions.

[Chemical constituents from Cinnamomi Ramulus decoction].

Six compounds were isolated from the ethyl acetate extracts of Cinnamomi Ramulus decoction by RP-18, silica gel, Sephadex LH-20 column chromatography, together with prep-HPLC methods. Based on HR-ESI-MS, MS, 1D and 2D NMR spectral analyses, the structures of the six compounds were identified as 4,5,10,11-tetrahydroxybisabol-7-ene(1), 4,5,10,11-tetrahydroxybisabolin(2), 1-phenyl-1,2,3-glycerol(3),(+)-lyoniresinol(4), benzoic acid(5), and decumbic acid(6). Compound 1 was a new bisabolene-type sesquiterpene, and compounds 2 and 3 were isolated from the Cinnamomi Ramulus for the first time. Moreover, the bisabolene-type sesquiterpene(2) was assayed for its anti-inflammatory activity and cytotoxicity to human pancreatic cancer cells(PANC-1 cells). RESULTS:: showed that compound 2 exhibited an inhibitory rate of 32.9% on nitric oxide(NO) at a dose of 40 µmol·L~(-1) and a proliferation inhibition rate of 14.5% against PANC-1 cells at a dose of 20 µmol·L~(-1). It did not demonstrate significant activity.

Differential responses of soil bacteria, fungi and protists to root exudates and temperature.

The impact of climate warming on soil microbes has been well documented, with studies revealing its effects on diversity, community structure and network dynamics. However, the consistency of soil microbial community assembly, particularly in response to diverse plant root exudates under varying temperature conditions, remains an unresolved issue. To address this issue, we employed a growth chamber to integrate temperature and root exudates in a controlled experiment to examine the response of soil bacteria, fungi, and protists. Our findings revealed that temperature independently regulated microbial diversity, with distinct patterns observed among bacteria, fungi, and protists. Both root exudates and temperature significantly influenced microbial community composition, yet interpretations of these factors varied among prokaryotes and eukaryotes. In addition to phototrophic bacteria and protists, as well as protistan consumers, root exudates determined to varying degrees the enrichment of other microbial functional guilds at specific temperatures. The effects of temperature and root exudates on microbial co-occurrence patterns were interdependent; root exudates primarily simplified the network at low and high temperatures, while responses to temperature varied between single and mixed exudate treatments. Moreover, temperature altered the composition of keystone species within the microbial network, while root exudates led to a decrease in their number. These results emphasize the substantial impact of plant root exudates on soil microbial community responses to temperature, underscoring the necessity for future climate change research to incorporate additional environmental variables.

Ex vivo MFG-E8 treatment improves the function of lungs procured from cardiac death donors in preclinical porcine model.

Ex vivo lung perfusion (EVLP) is a promising technology that allows the re-evaluation of donor lungs and has the potential to improve marginal lung reconditioning. The present study focused on the effects of milk fat globule epidermal growth factor 8 (MFG-E8) on the function of donation after circulatory death (DCD) lungs during EVLP and transplant reperfusion. Domestic swine were assigned to 4 groups. In the control group, the donor lungs lacking warm ischemia were preserved in Perfadex for 4 h. The swine in the other three groups underwent hypoxic arrest, followed by 1 h of warm ischemia. The DCD lungs were procured and randomly divided into three groups: cold static preservation (DCD-CSP) group, DCD-EVLP group, and DCD-MFG-E8 group. The left lung of all groups was transplanted and reperfused. During EVLP and reperfusion, lung functions and pathological evaluations were performed. Treatment with MFG-E8 resulted in significantly improved blood oxygenation. The mean pulmonary artery pressure, peak airway pressure, and expression of IL-1ß, IL-6, and IL-12 were significantly lower but IL-10 was higher in the DCD -MFG-E8 group. Furthermore, the lung injury severity score, pulmonary edema, and wet-to-dry weight ratio were also reduced in MFG-E8-treated lungs. However, the pulmonary vascular resistance and expression of TNF-α did not differ from the DCD -EVLP group but were significantly lower than in the DCD -CSP group. Adding MFG-E8 into the perfusate during EVLP obtains optimal graft function of lungs from DCD. This finding, if confirmed clinically, can be applied to recondition grafts and expanded use of DCD lungs.

Clinical efficacy and pain control of diode laser-assisted flap surgery in the treatment of chronic periodontitis:A systematic review and meta-analysis.

Objective: To assess the diode laser-assisted periodontal flap surgery's clinical effectiveness and postoperative pain management in treating chronic periodontitis, and to offer evidence-based medical justification for the procedure's clinical use. Data sources and study selection: In this study, a computer combined with manual search was used to search for articles on diode laser-assisted periodontal flap surgery for the treatment of chronic periodontitis published from the establishment of the database to September 2023. The databases searched included China Academic Journal Full Text Database (CNKI), China Biomedical Literature Database (CBM), Chinese Science and Technology Journal Database (VIP), Wanfang Database, PubMed, Web of science, Cochrane Library, Embase, and Scopus. Two researchers independently performed the screening and study selection, following the inclusion and exclusion standards to extract basic information and required data. Meta-analysis of the included literature was performed using Revman V5.4 software. Result: Thirteen articles were analyzed. Meta-analysis showed that the use of the diode laser was effective in reducing patients' probing pocket depth (PPD) at 3 and 6 months postoperatively (3 months: MD = -0.46, 95 % CI = [-0.89, -0.03], P = 0.04; 6 months: MD = -0.35, 95 % CI = [-0.63, -0.06], P = 0.02), was able to effectively improve 3 month clinical attachment level (CAL) (MD = -0.36, 95 % CI = [-0.66, -0.06], P = 0.02), and was able to promote wound healing and reduce patients' early postoperative pain (MD = 0.67, 95 % CI = [0.01, 1.32], P = 0.05; MD = -1.67, 95 % CI = [-2.23, -1.00], and P < 0. 001), while for gingival index (GI), the use of diode laser did not have a significant effect. Conclusions: The available evidence suggests that the use of a diode laser adjunct is effective in reducing PPD, improving CAL, promoting wound healing, and reducing early postoperative pain in patients compared with flap application alone; however, for GI, diode lasers did not show any improvements. Clinical significance: Periodontal flap surgery fails to eliminate microorganisms from the soft tissue wall, potentially leading to recolonization, reinfection, and accompanying side effects such as pain and swelling. The use of a diode laser reduces PPD, improves CAL, and relieves early postoperative pain.