Development and validation of a machine learning-based predictive model for assessing the 90-day prognostic outcome of patients with spontaneous intracerebral hemorrhage.

BACKGROUND: Spontaneous intracerebral hemorrhage (sICH) is associated with significant mortality and morbidity. Predicting the prognosis of patients with sICH remains an important issue, which significantly affects treatment decisions. Utilizing readily available clinical parameters to anticipate the unfavorable prognosis of sICH patients holds notable clinical significance. This study employs five machine learning algorithms to establish a practical platform for the prediction of short-term prognostic outcomes in individuals afflicted with sICH. METHODS: Within the framework of this retrospective analysis, the model underwent training utilizing data gleaned from 413 cases from the training center, with subsequent validation employing data from external validation center. Comprehensive clinical information, laboratory analysis results, and imaging features pertaining to sICH patients were harnessed as training features for machine learning. We developed and validated the model efficacy using all the selected features of the patients using five models: Support Vector Machine (SVM), Logistic Regression (LR), Random Forest (RF), XGboost and LightGBM, respectively. The process of Recursive Feature Elimination (RFE) was executed for optimal feature screening. An internal five-fold cross-validation was employed to pinpoint the most suitable hyperparameters for the model, while an external five-fold cross-validation was implemented to discern the machine learning model demonstrating the superior average performance. Finally, the machine learning model with the best average performance is selected as our final model while using it for external validation. Evaluation of the machine learning model's performance was comprehensively conducted through the utilization of the ROC curve, accuracy, and other relevant indicators. The SHAP diagram was utilized to elucidate the variable importance within the model, culminating in the amalgamation of the above metrics to discern the most succinct features and establish a practical prognostic prediction platform. RESULTS: A total of 413 patients with sICH patients were collected in the training center, of which 180 were patients with poor prognosis. A total of 74 patients with sICH were collected in the external validation center, of which 26 were patients with poor prognosis. Within the training set, the test set AUC values for SVM, LR, RF, XGBoost, and LightGBM models were recorded as 0.87, 0.896, 0.916, 0.885, and 0.912, respectively. The best average performance of the machine learning models in the training set was the RF model (average AUC: 0.906 ± 0.029, P < 0.01). The model still maintains a good performance in the external validation center, with an AUC of 0.817 (95% CI 0.705-0.928). Pertaining to feature importance for short-term prognostic attributes of sICH patients, the NIHSS score reigned supreme, succeeded by AST, Age, white blood cell, and hematoma volume, among others. In culmination, guided by the RF model's variable importance weight and the model's ROC curve insights, the NIHSS score, AST, Age, white blood cell, and hematoma volume were integrated to forge a short-term prognostic prediction platform tailored for sICH patients. CONCLUSION: We constructed a prediction model based on the results of the RF model incorporating five clinically accessible predictors with reliable predictive efficacy for the short-term prognosis of sICH patients. Meanwhile, the performance of the external validation set was also more stable, which can be used for accurate prediction of short-term prognosis of sICH patients.

The targeting of DAPK1 with miR-190a-3p promotes autophagy in trophoblast cells.

Pre-eclampsia (PE) is a dangerous pathological status that occurs during pregnancy and is a leading reason for both maternal and fetal death. Autophagy is necessary for cellular survival in the face of environmental stress as well as cellular homeostasis and energy management. Aberrant microRNA (miRNA) expression is crucial in the pathophysiology of PE. Although studies have shown that miRNA (miR)-190a-3p function is tissue-specific, the precise involvement of miR-190a-3p in PE has yet to be determined. We discovered that miR-190a-3p was significantly lower and death-associated protein kinase 1 (DAPK1) was significantly higher in PE placental tissues compared to normal tissues, which is consistent with the results in cells. The luciferase analyses demonstrated the target-regulatory relationship between miR-190a-3p and DAPK1. The inhibitory effect of miR-190a-3p on autophagy was reversed by co-transfection of si-DAPK1 and miR-190a-3p inhibitors. Thus, our data indicate that the hypoxia-dependent miR-190a-3p/DAPK1 regulatory pathway is implicated in the development and progression of PE by promoting autophagy in trophoblast cells.

Design, synthesis, biological evaluation of novel piperidine-based derivatives as potent poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a crucial member of DNA repair enzymes responsible for repairing DNA single-strand breaks. Developing PARP inhibitors based on synthetic lethality strategies is an effective approach for treating breast cancer and other diseases. In this study, a series of novel piperidine-based benzamide derivatives were designed and synthesized using structure-based drug design principles. The anticancer activities of these compounds were evaluated against five human cancer cell lines (MDA-MB-436, CAPAN-1, SW-620, HepG2, SKOV3, and PC3) and the preliminary structure-activity relationships were delineated. Among the compounds, 6a and 15d demonstrated potent antiproliferative effects against MDA-MB-436 cells with IC50 values of 8.56 ± 1.07 µM and 6.99 ± 2.62 µM, respectively. Furthermore, both compounds exhibited excellent inhibitory activity against PARP-1, with IC50 values of 8.33 nM and 12.02 nM, respectively. Mechanistic investigations revealed that 6a and 15d effectively inhibited colony formation and cell migration of HCT116 cells. Moreover, they induced apoptosis by upregulating the expression of Bax and cleaved Caspase-3, while downregulating the expression of Caspase-3 and Bcl-2 in HCT116 cells. Based on its impressive pharmacodynamic data in vitro, we conducted a study to evaluate the efficacy of 15d in a xenograft tumor model in mice when used in combination with cytotoxic agents. Collectively, these findings suggest that 15d could be promising drug candidates worthy of further investigation.

Metagenome reveals the possible mechanism that microbial strains promote methanogenesis during anaerobic digestion of food waste.

For better understanding the mechanism of microbial strains promoting methane production, four strains Hungatella xylanolytica A5, Bacillus licheniformis B1, Paraclostridium benzoelyticum C2 and Advenella faeciporci E1 were inoculated into anaerobic digestion systems. After bioaugmentation, the cumulative methane production of A5, B1, C2 and E1 groups elevated by 11.68%, 8.20%, 18.21% and 15.67% compared to CK group, respectively. The metagenomic analysis revealed that the species diversity and uniformity of the experimental groups was improved, and hydrolytic acidifying bacteria, represented by Clostridiaceae, Anaerolineaceae and Oscillospiraceae, and methanogens, such as Methanotrichaceae and Methanobacteriaceae, were enriched. Meanwhile, the abundance of key genes in carbohydrate, pyruvate and methane metabolism was increased in the inoculated groups, providing reasonable reasons for more methane production. The strengthening mechanism of microbial strains in this study offered a theoretical foundation for selecting a suitable bioaugmentation strategy to solve the problems of slow start-up and low methane production in anaerobic digestion.

A pig model of symptomatic spinal epidural hematoma.

PURPOSE: The purpose of this study was to establish an animal model capable of simulating the development and decompression process of symptomatic spinal epidural hematoma (SSEH). METHODS: A total of 16 male Bama miniature pigs were included in this study and randomly allocated into four groups: Group A (4 h 20 mmHg hematoma compression), Group B (4 h 24 mmHg hematoma compression), Group C (4 h 28 mmHg hematoma compression), and Group Sham (control). Real-time intra-wound hematoma compression values were obtained using the principle of connectors. Electrophysiological analyses, including the latency and amplitude of somatosensory evoked potentials (SSEP) and motor evoked potentials (MEP), along with behavioral observations (Tarlov score), were performed to assess this model. RESULTS: ANOVA tests demonstrated significant differences in the latency and relative amplitude of SSEP and MEP between Groups C and Sham after 4 h of hematoma compression and one month after surgery (P < 0.01). Behavioral assessments 8 h after surgery indicated that animals subjected to 28 mmHg hematoma compression suffered the most severe spinal cord injury. Pearson correlation coefficient test suggested a negative correlation between the epidural pressure and Tarlov score (r = -0.700, p < 0.001). With the progression of compression and the escalation of epidural pressure, the latency of SSEP and MEP gradually increased, while the relative amplitude gradually decreased. CONCLUSIONS: When the epidural pressure reaches approximately 24 mmHg, the spinal cord function occurs progressive dysfunction. Monitoring epidural pressure would be an effective approach to assist to identify the occurrence of postoperative SSEH.

Complications and local recurrence of chondrosarcoma and chordoma treated by total tumor resection in thoracic and lumbar spine.

BACKGROUND: En bloc resection of spinal tumors is challenging and associated with a high incidence of complications; however, it offers the potential to reduce the risk of recurrence when a wide margin is achieved. This research aims to investigate the safety and efficacy of en bloc resection in treating thoracic and lumbar chondrosarcoma/chordoma. METHODS: Data from patients diagnosed with chondrosarcoma and chordoma in the thoracic or lumbar region, who underwent total en bloc or piecemeal resection at our institution over a 7-year period, were collected and regularly followed up. The study analyzed overall perioperative complications and compared differences in complications and local tumor recurrence between the two surgical methods. RESULTS: Seventeen patients were included, comprising 12 with chondrosarcoma and 5 with chordoma. Among them, 5 cases underwent intralesional piecemeal resection, while the remaining 12 underwent planned en bloc resection. The average surgical time was 684 min (sd = 287), and the mean estimated blood loss was 2300 ml (sd = 1599). Thirty-five complications were recorded, with an average of 2.06 perioperative complications per patient. 82% of patients (14/17) experienced at least one perioperative complication, and major complications occurred in 64.7% (11/17). Five patients had local recurrence during the follow-up, with a mean recurrence time of 16.2 months (sd = 7.2) and a median recurrence time of 20 months (IQR = 12.5). Hospital stays, operation time, blood loss, and complication rates did not significantly differ between the two surgical methods. The local recurrence rate after en bloc resection was lower than piecemeal resection, although not statistically significant (P = 0.067). CONCLUSIONS: The complication rates between the two surgical procedures were similar. Considering safety and local tumor control, en bloc resection is recommended as the primary choice for patients with chondrosarcoma/chordoma in the thoracic and lumbar regions who are eligible for this treatment.

Report of Citrus tristeza virus in Diaphorina citri (Hemiotera: Liviidae) insects of different sexes, color morphs, and developmental stages.

Diaphorina citri, also known as the Asian citrus psyllid, is the main vector of 'Candidatus Liberibacter asiaticus' (CLas) associated with citrus Huanglongbing. It has been reported that D. citri could also be infected by Citrus tristeza virus (CTV), a virus that has been previously reported to be vectored by certain aphid species. In this study, the CTV and CLas profiles in different organs, color variants, developmental stages, or sexes of D. citri insects were analyzed. Although no significant differences were found between nymphs and adults in CTV titers, we found that the third instar nymph of D. citri was more efficient in CTV and CLas acquisition compared to the fourth and fifth instars and adults. With the instars of D. citri development, the relationship between the acquiring of CTV and CLas by D. citri seemed to follow an inverse trend, with the titer of CLas increased and the titer of CTV decreased. No significant differences were observed between the 2 sexes of D. citri in acquiring either CTV or CLas titers in the field. However, no differences were drawn among the 3 color morph variants for CTV titers. CTV titers in the midguts of adult D. citri were significantly higher than those in the salivary glands. Both CTV-positive incidence and CTV titers in the midguts of adult D. citri increased with increasing exposure periods. This study provides new data to deepen our understanding of the CTV-involved interaction between D. citri and CLas.

[Clinical outcomes of 3D-printing stand-alone artificial vertebral body in anterior cervical surgeries].

OBJECTIVE: To explore the short-term outcomes of 3D-printing stand-alone artificial vertebral body (AVB) in the surgical procedure of anterior cervical corpectomy and fusion (ACCF). METHODS: Following the proposal of IDEAL (idea, development, exploration, assessment, and long-term follow-up) framework, we designed and conducted this single-armed, retrospective cohort study. The patients with cervical spondylotic myelopathy were recruited, and these patients exclusively received the surgical procedure of single-level ACCF in our single center. After the process of corpectomy, the size was tailored using different trials and the most suitable stand-alone AVB was then implanted. This AVB was manufactured by the fashion of 3D-printing. Two pairs of screws were inserted in an inclined way into the adjacent vertebral bodies, to stabilize the AVB. The participants were regularly followed-up after the operation. Their clinical data were thoroughly reviewed. We assessed the neurological status according to Japanese Orthopedic Association (JOA) scale. We determined the fusion based on imaging examination six months after the operation. The recorded clinical data were analyzed using specific software and they presented in suitable styles. Paired t test was employed in comparison analysis. RESULTS: In total, there were eleven patients being recruited eventually. The patients were all followed up over six months after the operation. The mean age of the cohort was (57.2±10.2) years. The mean operation time was (76.1±23.1) min and the median bleeding volume was 150 (100, 200) mL. The postoperative course was uneventful for all the cases. Dysphagia, emergent hematoma, and deterioration of neurological function did not occur. Mean JOA scores were 13.2±2.2 before the operation and 16.3±0.8 at the final follow-up, which were significantly different (P < 0.001). The mean recovery rate of neurological function was 85.9%. By comparing the imaging examinations postoperatively and six months after the operation, we found that the average subsidence length was (1.2±1.1) mm, and that there was only one cases (9.1%) of the severe subsidence (>3 mm). We observed significant improvement of cervical lordosis after the operation (P=0.013). All the cases obtained solid fusion. CONCLUSION: 3D-printing stand-alone AVB presented favorable short-term outcome in one-level ACCF in this study. The fusion rate of this zero-profile prosthesis was satisfactory and the complication rate was relatively low.

A Zeolitic Octahedral Metal Oxide with Ultrahigh Porosity for High-temperature and High-humidity Alkyne/Alkene Separation.

Zeolitic octahedral metal oxide is a newly synthesized all-inorganic zeolitic material and has been used for adsorption, separation, and catalysis. Herein, a new zeolitic octahedral metal oxide was synthesized and characterized. The porous framework was established through the assembly of [P2Mo13O50] clusters with PO4 linkers. Guest molecules occupied the framework, which could be removed through heat treatment, thereby opening the micropores. The pore characteristics were controlled by the cations within the micropore, enabling the adjustment of the interactions with alkynes and alkenes. This resulted in good separation performance of ethylene/acetylene and propylene/propyne even under high temperature and humidity conditions. The high stability of the material enabled the efficient recovery and reuse without discernible loss in the separation performance. Due to the relatively weak interaction between the adsorbed alkyne and the framework, the adsorbent facilitated the recovery of a highly pure alkyne. This feature enhances the practical applicability of the material in various industrial processes.

Baseline free water within the visual processing system predicts future psychosis in Parkinson disease.

BACKGROUND AND PURPOSE: As psychosis is associated with decreased quality of life, increased institutionalization, and mortality in Parkinson disease (PD), it is essential to identify individuals at risk for future psychosis. This longitudinal study aimed to investigate whether diffusion tensor imaging (DTI) metrics of white matter hold independent utility for predicting future psychosis in PD, and whether they could be combined with clinical predictors to improve the prognostication of PD psychosis. METHODS: This study included 123 newly diagnosed PD patients collected in the Parkinson's Progression Markers Initiative. Tract-based spatial statistics were used to compare baseline DTI metrics between PD patients who developed psychosis and those who did not during follow-up. Binary logistic regression analyses were performed to identify the clinical and white matter markers predictive of psychosis. RESULTS: Among DTI measures, both higher baseline whole brain (odds ratio [OR] = 1.711, p = 0.016) free water (FW) and visual processing system (OR = 1.680, p < 0.001) FW were associated with an increased risk of future psychosis. Baseline FW remained a significant indicator of future psychosis in PD after controlling for clinical predictors. Moreover, the accuracy of prediction of psychosis using clinical predictors alone (area under the curve [AUC] = 0.742, 95% confidence interval [CI] = 0.655-0.816) was significantly improved by the addition of the visual processing system FW (AUC = 0.856, 95% CI = 0.781-0.912; Delong method, p = 0.022). CONCLUSIONS: Baseline FW of the visual processing system incurs an independent risk of future psychosis in PD, thus providing an opportunity for multiple-modality marker models to include a white matter marker.

Complications and prognosis of primary thoracic and lumbar giant cell tumors treated by total tumor resection.

BACKGROUND: Spinal giant cell tumor (SGCT) is a relatively rare primary tumor. En bloc resection is the preferred surgical procedure for it due to its aggressiveness, meanwhile leading to more complications. We reported the characteristics of perioperative complications and local control of total tumor resection including en bloc resection and piecemeal resection for primary thoracic and lumbar spinal giant cell tumors in a single center over 10 years. METHODS: This is a retrospective cross-sectional and cohort study. Forty-one consecutive patients with SGCTs who underwent total tumor resection from 2010 to 2020 at our institution and were followed up for at least 24 months were reviewed. Surgery data, complication characteristics and local tumor control were collected and compared by different surgical procedure. RESULTS: Forty-one patients were included, consisting of 18 males and 23 females, with a mean age of 34.2 years. Thirty-one had thoracic vertebra lesions, and 10 had lumbar vertebra lesions. Thirty-five patients were primary cases, and 6 patients were recurrent cases. Eighteen patients were treated by total en bloc spondylectomy (TES), 12 patients underwent en bloc resection according to WBB surgical system, and 11 patients underwent piecemeal resection. The average surgical time was 498 min, and the mean estimated blood loss was 2145 ml. A total of 58 complications were recorded, and 30 patients (73.2%) had at least one perioperative complication. All patients were followed up after surgery for at least 2 years. A total of 6 cases had postoperative internal fixation failure, and 4 cases presented local tumor recurrence (9.8%). CONCLUSIONS: Although the surgical technique is difficult and accompanied by a high rate of perioperative complications, en bloc resection can achieve favorable local control in SGCT. When it is too difficult to complete en bloc resection, thoroughly piecemeal resection without residual is also acceptable, given the relatively low recurrence rate.

Dosimetry impact of distinct gating strategies in cine MR image-guided breath-hold pancreatic cancer radiotherapy.

PURPOSE: To investigate the dosimetry effects of different gating strategies in cine magnetic resonance imaging (MRI)-guided breath-hold pancreatic cancer radiotherapy. METHODS: Two cine MRI-based gating strategies were investigated： a tumor contour-based gating strategy at a gating threshold of 0-5% and a tumor displacement-based gating strategy at a gating threshold of 3-5 mm. The cine MRI videos were obtained from 17 pancreatic cancer patients who received MRI-guided radiation therapy. We calculated the tumor displacement in each cine MR frame that satisfied the gating threshold and obtained the proportion of frames with different displacements. We generated IMRT and VMAT plans using a 33 Gy prescription, and motion plans were generated by adding up all isocenter-shift plans corresponding to different tumor displacements. The dose parameters of GTV, PTV, and organs at risk (OAR) were compared between the original and motion plans. RESULTS: In both gating strategies, the difference was significant in PTV coverage but not in GTV coverage between the original and motion plans. OAR dose parameters deteriorate with increasing gating threshold. The beam duty cycle increased from 19.5±14.3% (median 18.0%) to 60.8±15.6% (61.1%) for gating thresholds from 0% to 5% in tumor contour-based gating and from 51.7±11.5% (49.7%) to 67.3±12.4% (67.1%) for gating thresholds from 3 to 5 mm in tumor displacement-based gating. CONCLUSION: In tumor contour-based gating strategy, the dose delivery accuracy deteriorates while the dose delivery efficiency improves with increasing gating thresholds. To ensure treatment efficiency, the gating threshold might be no less than 3%. A threshold up to 5% may be acceptable in terms of the GTV coverage. The displacement-based gating strategy may serve as a potential alternative to the tumor contour based gating strategy, in which the gating threshold of approximately 4 mm might be a good choice for reasonably balancing the dose delivery accuracy and efficiency.

[Application of brain functional connectivity and nonlinear dynamic analysis in brain function assessment for infants with controlled infantile spasm]. / 脑功能连接及非线性动力学分析在发作控制的婴儿痉挛症患儿脑功能评估中的应用.

OBJECTIVES: To investigate the role of brain functional connectivity and nonlinear dynamic analysis in brain function assessment for infants with controlled infantile spasm (IS). METHODS: A retrospective analysis was performed on 14 children with controlled IS (IS group) who were admitted to the Department of Neurology, Anhui Provincial Children's Hospital, from January 2019 to January 2023. Twelve healthy children, matched for sex and age, were enrolled as the control group. Electroencephalogram (EEG) data were analyzed for both groups to compare the features of brain network, and nonlinear dynamic indicators were calculated, including approximate entropy, sample entropy, permutation entropy, and permutation Lempel-Ziv complexity. RESULTS: Brain functional connectivity showed that compared with the control group, the IS group had an increase in the strength of functional connectivity, and there was a significant difference between the two groups in the connection strength between the Fp2 and F8 channels (P<0.05). The network stability analysis showed that the IS group had a significantly higher network stability than the control group at different time windows (P<0.05). The nonlinear dynamic analysis showed that compared with the control group, the IS group had a significantly lower sample entropy of Fz electrode (P<0.05). CONCLUSIONS: Abnormalities in brain network and sample entropy may be observed in some children with controlled IS, and it is suggested that quantitative EEG analysis parameters can serve as neurological biomarkers for evaluating brain function in children with IS.

A sheep model of chronic cervical compressive myelopathy via an implantable wireless compression device.

PURPOSE: This study aimed to establish an animal model in which we can precisely displace the spinal cord and therefore mimic the chronic spinal compression of cervical spondylotic myelopathy. METHODS: In vivo intervertebral compression devices (IVCDs) connected with subcutaneous control modules (SCCMs) were implanted into the C2-3 intervertebral disk spaces of sheep and connected by Bluetooth to an in vitro control system. Sixteen sheep were divided into four groups: (Group A) control; (Group B) 10-week progressive compression, then held; (Group C) 20-week progressive compression, then held; and (Group D) 20-week progressive compression, then decompression. Electrophysiological analysis (latency and amplitude of the N1-P1-N2 wave in somatosensory evoked potentials, SEP), behavioral changes (Tarlov score), imaging test (encroachment ratio (ER) of intraspinal invasion determined by X-ray and CT scan), and histological examinations (hematoxylin and eosin, Nissl, and TUNEL staining) were performed to assess the efficacy of our model. RESULTS: Tarlov scores gradually decreased as compression increased with time and partially recovered after decompression. The Pearson correlation coefficient between ER and time was r = 0.993 (p < 0.001) in Group B at 10 weeks and Groups C and D at 20 weeks. And ER was negatively correlated with the Tarlov score (r = -0.878, p < 0.001). As compression progressed, the SEP latency was significantly extended (p < 0.001), and the amplitude significantly decreased (p < 0.001), while they were both partially restored after decompression. The number of abnormal motor neurons and TUNEL-positive cells increased significantly (p < 0.001) with compression. CONCLUSION: Our implantable and wireless intervertebral compression model demonstrated outstanding controllability and reproducibility in simulating chronic cervical spinal cord compression in animals.

Automatic treatment planning for cervical cancer radiation therapy using direct three-dimensional patient anatomy match.

PURPOSE: Current knowledge-based planning methods for radiation therapy mainly use low-dimensional features extracted from contoured structures to identify geometrically similar patients. Here, we propose a knowledge-based treatment planning method where the anatomical similarity is quantified by the rigid registration of the three-dimensional (3D) planning target volume (PTV) and organs at risks (OARs) between an incoming patient and database patients. METHODS: A database that contains PTV and OARs contours from 81 cervical cancer radiation therapy patients was established. To identify the anatomically similar patients, the PTV of the new patient was registered to each PTV in the database and the Dice similarity coefficients were calculated for the PTV, rectum, and bladder between the new patient and database patients. Then the top 20 patients in the PTV match and top 3 patients in the subsequent bladder or rectum match were selected. The best dose-volume histogram parameters from the top three patients were applied as the dose constraints to the automatic plan optimization. A fast Fourier transform algorithm was developed to accelerate the 3D PTV registration process run through the database. The entire treatment planning process was automated using in-house customized Pinnacle scripts. The automatic plans were generated for 20 patients using leave-one-out scheme and were evaluated against the corresponding clinical plans. RESULTS: The automatic plans significantly reduced rectum and bladder V 50 Gy ${V_{50\,\,{\rm{Gy}}}}$ by 11.79% ± 5.2% (p < 0.01) and 2.85% ± 3.16% (p < 0.01), respectively. The dose parameters achieved for the PTV and other OARs were comparable to those in the clinical plans. The entire planning process, including both dose prediction and inverse optimization, costs about 6 min. CONCLUSIONS: The direct 3D contour match method utilizes the full spatial information of the PTV and OARs of interest and provides an intuitive measurement for patient plan anatomy similarity. The proposed automatic planning method can generate plans with better quality and higher efficiency.

Structural correlates underlying accelerated magnetic stimulation in Parkinson's disease.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique with great potential in the treatment of Parkinson's disease (PD). This study aimed to investigate the clinical efficacy of accelerated rTMS and to understand the underlying neural mechanism. In a double-blinded way, a total of 42 patients with PD were randomized to receive real (n = 22) or sham (n = 20) continuous theta-burst stimulation (cTBS) on the left supplementary motor area (SMA) for 14 consecutive days. Patients treated with real cTBS, but not with sham cTBS, showed a significant improvement in Part III of the Unified PD Rating Scale (p < .0001). This improvement was observed as early as 1 week after the start of cTBS treatment, and maintained 8 weeks after the end of the treatment. These findings indicated that the treatment response was swift with a long-lasting effect. Imaging analyses showed that volume of the left globus pallidus (GP) increased after cTBS treatment. Furthermore, the volume change of GP was mildly correlated with symptom improvement and associated with the baseline fractional anisotropy of SMA-GP tracts. Together, these findings implicated that the accelerated cTBS could effectively alleviate motor symptoms of PD, maybe by modulating the motor circuitry involving the SMA-GP pathway.

Zeolitic Vanadotungstates with Ultrahigh Porosities for Separation of Butane and Isobutane.

Zeolitic vanadotungstates with tunable microporosity have potential interests in gas separation. The pore openings of the materials are in between the diameters of normal butane and isobutane, which causes the materials only adsorb normal butane. The breakthrough experiments show that the materials effectively separate normal butane from the normal butane and isobutane mixture even at high temperatures. The robust materials can be reused without loss of the separation performance.

Network pharmacology-based study on the mechanism of scutellarin against zearalenone-induced ovarian granulosa cell injury.

Zearalenone(ZEA) is a kind of mycotoxin widely existing in nature, its toxic effects can lead to the reproductive disorders in humans and animals. The aim of this study was to investigate the mechanism of scutellarin against ovarian granulosa cell(GCs) injury induced by ZEA based on network pharmacology, molecular docking method. The results show that 293 drug targets of scutellarin were found from PhamMapper database, and 583 disease targets were selected from Genecards database. Finally, 57 scutellarin targets were obtained for the repair of GCs injury with gene intersection. The protein-protein interaction(PPI), gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) analysis indicated that MAPK signaling pathway was most likely activated by scutellarin. Scutellarin with JNK or Caspase-3 had minimal and negative free binding energy in molecular docking analysis, indicating that they might be the acting targets of scutellarin. Cell viability was significantly decreased in ZEA treated cells. However, GCs viability, the level of estradiol(E2) and progesterone(P4) were significantly increased with addition of scutellarin to ZEA treated cells. Western blot analysis showed that scutellarin significantly reduced the expression of JNK, c-jun and Cleaved-caspasee-3 in GCs compared with ZEA treatment. In conclusion, scutellarin could alleviate the ovarian GCs injury by down-regulating the expression of JNK, c-jun and Cleaved-caspase-3 through the activation of MAPK/JNK signaling pathway. Our results will provide a theoretical foundation for the treatment of reproductive disorders with scutellarin.

A Land of Controversy: Fibroblast Growth Factor-23 and Uremic Cardiac Hypertrophy.

Cardiac hypertrophy is a common feature in patients with CKD. Recent studies revealed that two phosphate regulators, fibroblast growth factor-23 and α-Klotho, are highly involved in the pathophysiologic process of CKD-induced cardiac hypertrophy. With decreasing renal function, elevated fibroblast growth factor-23 and decreased α-Klotho may contribute to cardiac hypertrophy by targeting the heart directly or by inducing systemic changes, such as vascular injury, hemodynamic disorders, and inflammation. However, several studies have demonstrated that disturbances in the fibroblast growth factor-23/α-Klotho axis do not lead to cardiac hypertrophy. In this review, we describe the cardiac effects of the fibroblast growth factor-23/α-Klotho axis and summarize recent progress in this field. In addition, we present not only the main controversies in this field but also provide possible directions to resolve these disputes.

A common variant of the NOTCH4 gene modulates functional connectivity of the occipital cortex and its relationship with schizotypal traits.

BACKGROUND: Schizotypal traits are considered as inheritable traits and the endophenotype for schizophrenia. A common variant in the NOTCH4 gene, rs204993, has been linked with schizophrenia, but the neural underpinnings are largely unknown. METHODS: In present study, we compared the differences of brain functions between different genotypes of rs204993 and its relationship with schizotypal traits among 402 Chinese Han healthy volunteers. The brain function was evaluated with functional connectivity strength (FCS) using the resting-state functional magnetic resonance image(rs-fMRI). The schizotypal traits were measured by the schizotypal personality questionnaire (SPQ). RESULTS: Our results showed that carriers with the AA genotype showed reduced FCS in the left occipital cortex when compared with carriers with the AG and GG genotypes, and the carriers with the AG genotype showed reduced FCS in the left occipital cortex when compared with carriers with the GG genotype. The FCS values in the left occipital lobe were negatively associated with the SPQ scores and its subscale scores within the carriers with the GG genotype, but not within the carriers with AA or AG genotype. CONCLUSION: Our results suggested that the common variant in the NOTCH4 gene, rs204993, modulates the function of the occipital cortex, which may contribute to schizotypal traits. These findings provide insight for genetic effects on schizotypal traits and its potential neural substrate.