Hippocampal Glutamate Levels and Their Correlation With Subregion Volume in School-Aged Children With MRI-Negative Epilepsy: A Preliminary Study.

BACKGROUND: Abnormal levels of glutamate constitute a key pathophysiologic mechanism in epilepsy. The use of glutamate chemical exchange saturation transfer (GluCEST) imaging to measure glutamate levels in pediatric epilepsy is rarely reported in research. PURPOSE: To investigate hippocampal glutamate level variations in pediatric epilepsy and the correlation between glutamate and hippocampal subregional volumes. STUDY TYPE: Cross-sectional, prospective. SUBJECTS: A total of 38 school-aged pediatric epilepsy patients with structurally normal MRI as determined by at least two independent radiologists (60% males; 8.7 ± 2.5 years; including 20 cases of focal pediatric epilepsy [FE] and 18 cases of generalized pediatric epilepsy [GE]) and 17 healthy controls (HC) (41% males; 9.0 ± 2.5 years). FIELD STRENGTH/SEQUENCE: 3.0 T; 3D magnetization prepared rapid gradient echo (MPRAGE) and 2D turbo spin echo GluCEST sequences. ASSESSMENT: The relative concentration of glutamate was calculated through pixel-wise magnetization transfer ratio asymmetry (MTRasym) analysis of the GluCEST data. Hippocampal subfield volumes were computed from MPRAGE data using FreeSurfer. STATISTICAL TESTS: This study used t tests, one-way analysis of variance, Kruskal-Wallis tests, and Pearson correlation analysis. P < 0.05 was considered statistically significant. RESULTS: The MTRasym values of both the left and right hippocampi were significantly elevated in GE (left: 2.51 ± 0.23 [GE] vs. 2.31 ± 0.12 [HCs], right: 2.50 ± 0.22 [GE] vs. 2.27 ± 0.22 [HCs]). The MTRasym values of the ipsilateral hippocampus were significantly elevated in FE (2.49 ± 0.28 [ipsilateral] vs. 2.29 ± 0.16 [HCs]). The MTRasym values of the ipsilateral hippocampus were significantly increased compared to the contralateral hippocampus in FE (2.49 ± 0.28 [ipsilateral] vs. 2.35 ± 0.34 [contralateral]). No significant differences in hippocampal volume were found between different groups (left hippocampus, P = 0.87; right hippocampus, P = 0.87). DATA CONCLUSION: GluCEST imaging have potential for the noninvasive measurement of glutamate levels in the brains of children with epilepsy. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Hierarchical Porous Carbon Supported Co2P2O7 Nanoparticles for Oxygen Evolution and Oxygen Reduction in a Rechargeable Zn-Air Battery.

The oxygen reduction/evolution reaction (ORR/OER) represents a pivotal process in metal-air batteries; however, it is constrained by the limitations of slow kinetics. Nevertheless, the creation of long-lasting and bifunctional catalysts represents a significant challenge. This study presents a series of hierarchical porous carbon-supported cobalt pyrophosphate (Co2P2O7-N/C-T) catalysts, prepared through the pyrolysis of porphyrin-based NTU-70 nanosheets with red phosphorus at varying temperatures. The Co2P2O7-N/C-800 not only demonstrates remarkable OER performance with an overpotential of only 290 mV at a current density of 10 mA cm-2 in 1 M KOH, but also exhibits an excellent ΔE of 0.74 V in 0.1 M KOH, which is lower than that of Pt/C + RuO2 (0.76 V). The utilization of Co2P2O7-N/C-800 as an air cathode in a rechargeable Zn-air battery (ZAB) results in a stable discharge voltage plateau of 1.405 V and a high gravimetric energy density of 801.2 mA h gZn-1. This work presents a promising strategy for the design of efficient bifunctional catalysts and demonstrates the critical importance of the interplay between the active center and the supported hierarchical porous carbon.

GluCEST Imaging and Structural Alterations of the Bilateral Hippocampus in First-Episode and Early-Onset Major Depression Disorder.

BACKGROUND: Glutamate dysregulation is one of the key pathogenic mechanisms of major depressive disorder (MDD), and glutamate chemical exchange saturation transfer (GluCEST) has been used for glutamate measurement in some brain diseases but rarely in depression. PURPOSE: To investigate the GluCEST changes in hippocampus in MDD and the relationship between glutamate and hippocampal subregional volumes. STUDY TYPE: Cross-sectional. SUBJECTS: Thirty-two MDD patients (34% males; 22.03 ± 7.21 years) and 47 healthy controls (HCs) (43% males; 22.00 ± 3.28 years). FIELD STRENGTH/SEQUENCE: 3.0 T; magnetization prepared rapid gradient echo (MPRAGE) for three-dimensional T1-weighted images, two-dimensional turbo spin echo GluCEST, and multivoxel chemical shift imaging (CSI) for proton magnetic resonance spectroscopy (1 H MRS). ASSESSMENT: GluCEST data were quantified by magnetization transfer ratio asymmetry (MTRasym ) analysis and assessed by the relative concentration of 1 H MRS-measured glutamate. FreeSurfer was used for hippocampus segmentation. STATISTICAL TESTS: The independent sample t test, Mann-Whitney U test, Spearman's correlation, and partial correlation analysis were used. P < 0.05 was considered statistically significant. RESULTS: In the left hippocampus, GluCEST values were significantly decreased in MDD (2.00 ± 1.08 [MDD] vs. 2.62 ± 1.41 [HCs]) and showed a significantly positive correlation with Glx/Cr (r = 0.37). GluCEST values were significantly positively correlated with the volumes of CA1 (r = 0.40), subiculum (r = 0.40) in the left hippocampus and CA1 (r = 0.51), molecular_layer_HP (r = 0.50), GC-ML-DG (r = 0.42), CA3 (r = 0.44), CA4 (r = 0.44), hippocampus-amygdala-transition-area (r = 0.46), and the whole hippocampus (r = 0.47) in the right hippocampus. Hamilton Depression Rating Scale scores showed significantly negative correlations with the volumes of the left presubiculum (r = -0.40), left parasubiculum (r = -0.47), and right presubiculum (r = -0.41). DATA CONCLUSION: GluCEST can be used to measure glutamate changes and help to understand the mechanism of hippocampal volume loss in MDD. Hippocampal volume changes are associated with disease severity. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Glutamate alterations in the premature infant brain during different gestational ages with glutamate chemical exchange saturation transfer imaging: a pilot study.

OBJECTIVES: To elucidate the change in glutamate levels in preterm infants at different gestational ages by glutamate chemical exchange saturated transfer (GluCEST) magnetic resonance imaging and to compare the difference in glutamate levels among different brain regions between very early preterm infants and middle and late preterm infants. METHODS: Fifty-three preterm infants (59% males; median gestational age = 33.6 weeks) underwent MRI, including conventional MRI and GluCEST. The original data were postprocessed in MATLAB. Correlation analysis was used to determine the relationship between the MTRasym and gestational age. The differences in MTRasym signals among different ROIs were statistically analysed by one-way analysis of variance (ANOVA). The MTRasym difference of the bilateral hemispherical ROI was compared by a paired T test. RESULTS: In all ROIs, glutamate concentration was positively correlated with gestational age. The glutamate concentration in the thalamus was higher than that in the frontal lobe in very early, middle and late preterm infants. A difference in glutamate concentration was not found in the bilateral ROIs. CONCLUSIONS: The concentration of glutamate in the brains of preterm infants of different gestational ages increased with gestational age, which may be one of the factors contributing to the higher incidence of neurodevelopmental dysfunction in very early preterm infants compared to that in middle and late preterm infants. Meanwhile, the glutamate concentrations among different brain regions were also diverse. KEY POINTS: • The glutamate concentration was positively correlated with gestational age in preterm infants of the brain. • Glutamate concentrations were dissimilar in different brain regions of preterm infants. • Glutamate concentration during the process of brain development in premature infants was not found to be asymmetric.

Preoperative transarterial chemoembolization with drug-eluting beads (DEB-TACE) in patients undergoing conversional hepatectomy: a propensity-score matching analysis.

OBJECTIVES: Patients with colorectal liver metastases (CRLM) who underwent hepatic resection after conversion therapy had a high recurrence rate of nearly 90%. Preoperative DEB-TACE has the potential to prevent postoperative recurrence which has not been elucidated. The objective of this study was to evaluate the safety and efficacy of preoperative DEB-TACE. MATERIALS AND METHODS: Patients with CRLM who underwent liver resection from June 1, 2016, to June 30, 2021, were collected and those who received conversional hepatectomy were included in this study. Patients with preoperative DEB-TACE were propensity-score matched in a 1:1 ratio to patients without preoperative DEB-TACE. Short-term outcomes and recurrence-free survival (RFS) were compared between the two groups. RESULTS: After PSM, 44 patients were included in each group. The toxicities of DEB-TACE were mild and could be managed by conservative treatment. Overall response rate (ORR) of conversion therapy (75.0% vs. 81.2%, p = 0.437) and postoperative complication of hepatic resection (27.3% vs. 20.5%, p = 0.453) were similar between the two groups. The median RFS of the DEB-TACE group (10.7 months, 95%CI: 6.6-14.8 months) was significantly longer than that of the control group (8.1 months, 95%CI: 3.4-12.8 months) (HR: 0.60, 95%CI: 0.37-0.95, p = 0.027). CONCLUSIONS: In patients who became resectable after conversion therapy, preoperative DEB-TACE might be a safe option to achieve longer RFS. KEY POINTS: • This is a propensity-score matching study comparing patients who underwent conversional hepatectomy with or without preoperative DEB-TACE. • The preoperative DEB-TACE was safe and with mild toxicities (without toxicities more than CTCAE grade 3). • The preoperative DEB-TACE significantly prolonged the RFS of those patients who underwent conversional hepatectomy (10.7 vs. 8.1 months, p = 0.027).

KLHL22 maintains PD-1 homeostasis and prevents excessive T cell suppression.

Aberrant programmed cell death protein 1 (PD-1) expression on the surface of T cells is known to inhibit T cell effector activity and to play a pivotal role in tumor immune escape; thus, maintaining an appropriate level of PD-1 expression is of great significance. We identified KLHL22, an adaptor of the Cul3-based E3 ligase, as a major PD-1-associated protein that mediates the degradation of PD-1 before its transport to the cell surface. KLHL22 deficiency leads to overaccumulation of PD-1, which represses the antitumor response of T cells and promotes tumor progression. Importantly, KLHL22 was markedly decreased in tumor-infiltrating T cells from colorectal cancer patients. Meanwhile, treatment with 5-fluorouracil (5-FU) could increase PD-1 expression by inhibiting the transcription of KLHL22. These findings reveal that KLHL22 plays a crucial role in preventing excessive T cell suppression by maintaining PD-1 expression homeostasis and suggest the therapeutic potential of 5-FU in combination with anti-PD-1 in colorectal cancer patients.

[The design of plantar pressure distribution monitoring system and preliminary clinical application].

Plantar pressure distribution can reflect the force of several key points on foot while standing and walking. A comprehensive understanding of the plantar pressure distribution makes great sense in the following aspects: the understanding of the normal foot biomechanics and function, clinical diagnosis, measurement of disease extent, postoperative efficacy evaluation, and rehabilitation research. A simple plantar pressure measurement device was designed in this study. This paper uses FlexiForce flexible sensor to pickup plantar pressure signal and USB A/D board to do data acquisition. The data are transferred into a laptop and processed by a VB-based software which can display, remember and replay the data. We chose patients with hallux valgus and normal people to measure the pressure distribution and make contrast analysis of plantar pressure with this device. It can be concluded that people with hallux valgus have higher pressure on the second metatarsophalangeal joint and the distribution move outward. The plantar pressure of patients postoperative could be greatly improved compared to the preoperative. The function of this device has been confirmed.

[Construction and validation of clinical prediction model of acupuncture and moxibustion for Bell's palsy].

OBJECTIVE: To establish and validate a clinical prediction model of acupuncture and moxibustion for Bell's palsy so as to provide a tool for predicting the effect of acupuncture and moxibustion on Bell's palsy. METHODS: A total of 269 patients with Bell's palsy were collected from department of acupuncture, moxibustion and tuina, Shengli Oilfield Central Hospital, neurology department, Shenxian County Central Hospital and department of rehabilitation medicine, Dongying Municipal Hospital of TCM from June 2018 to June 2023. All of these cases were treated with acupuncture and moxibustion. Of them, 182 cases, from department of acupuncture, moxibustion and tuina, Shengli Oilfield Central Hospital and neurology department, Shenxian County Central Hospital, were randomized into a training group (128 cases) and an internal validation group (54 cases); 87 cases from department of rehabilitation medicine, Dongying Municipal Hospital of TCM were assigned to an external validation group. The clinical data of all of the cases were extracted from the electronic medical record information platform. Using SPSS25.0 and R4.2.3, through univariate and multivariate Logistic regression analysis, the independent factors influencing the effects of acupuncture and moxibustion on Bell's palsy were identified. By means of internal and external validations, the receiver operating characteristic curve (ROC), the goodness-of-fit curve (GFC) and the decision curve analysis (DCA) were plotted. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the model were calculated; and its comprehensive performance was evaluated. RESULTS: The results of the multivariate Logistic regression analysis showed that the independent factors for the unsatisfactory effect on Bell's palsy were advanced age, severe symptoms before treatment, no use of steroids within 72 h of onset, and lack of acupuncture-moxibustion therapy during the acute phase or single acupuncture-moxibustion protocol (P<0.05, P<0.01). Based on these factors, nomogram model and online columnar plot prediction tool (https://bmuchen.shinyapps.io/dynnomapp/) were established. The area under the ROC curve of the model was 0.921 (95% CI: 0.877, 0.966), 0.876 (95% CI: 0.787, 0.966), and 0.846 (95% CI: 0.766, 0.926) in the training group, the internal validation group, and the external validation group, respectively, indicating good predictive value. The model showed a satisfactory calibration curve alignment. The decision threshold in the range of 0 to 0.8 provided clinical benefits for participants. The model exhibited the sensitivity from 65.9% to 88.0%, the specificity ranging from 77.3% to 90.7%, the accuracy from 77.8% to 85.9%, the positive predictive value from 83.3% to 90.1%, and the negative predictive value from 70.8% to 78.7%. The comprehensive evaluation indicated a satisfactory clinical application value of the model. CONCLUSION: The clinical prediction model of acupuncture and moxibustion for Bell's palsy is valuable in its practice and promotion to a certain extent. The predicted results are conductive to clinicians' judgement of the effect of acupuncture and moxibustion for this disease and making effective and high-quality clinical decisions, as well as formulating the optimal therapeutic regimen.

The contribution of natural and anthropogenic causes to soil acidification rates under different fertilization practices and site conditions in southern China.

Excessive application of mineral fertilizers has accelerated soil acidification in China, affecting crop production when the pH drops below a critical value. However, the contributions of natural soil acidification, induced by leaching of bicarbonate, and anthropogenic causes of soil acidification, induced by nitrogen (N) transformations and removal of base cations over acid anions, are not well quantified. In this study, we quantified soil acidification rates, in equivalents (eq) of acidity, by assessing the inputs and outputs of all major cations and anions, including calcium, magnesium, potassium, sodium, ammonium, nitrate, bicarbonate, sulphate, phosphate and chloride, for 13 long-term experimental sites in southern China. The acidification rates strongly varied among fertilizer treatments and with the addition of animal manure. Bicarbonate leaching was the dominant acid production process in calcareous soils (23 keq ha-1 yr-1) and in non-calcareous paddy soils (9.6 keq ha-1 yr-1), accounting for 80 % and 68 % of the total acid production rate, respectively. The calcareous soils were strongly buffered, and acidification led no or a limited decline in pH. In contrast, N transformations were the most important driver for soil acidification at one site with upland crops on a non-calcareous soil, accounting for 72 % of total acid production rate of 8.4 keq ha-1 yr-1. In this soil, the soil pH considerably decreased being accompanied by a substantial decline in exchangeable base cation. Reducing the N surplus decreased the acidification rate with 10 to 54 eq per kg N surplus with the lowest value occurring in paddy soils and the highest in the upland soil. The use of manure, containing base cations, partly mitigated the acidifying impact of N fertilizer inputs and crop removal, but enhanced phosphorus (P) accumulation. Combining mineral fertilizer, manure and lime in integrative management strategies can mitigate soil acidification and minimize N and P losses.

Major drivers of soil acidification over 30 years differ in paddy and upland soils in China.

Elevated nitrogen (N) fertilization has largely increased crop production in China, but also increased acidification risks, thereby threatening crop yields. However, natural soil acidification due to bicarbonate (HCO3) leaching and base cation (BC) removal by crop harvest also affect soil acidity whereas the input of HCO3 and BC via fertilizers and manure counteract soil acidification. Insights in rates and drivers of soil acidification in different land use types is too limited to support crop- and site-specific mitigation strategies. In this study, we assessed the historical changes in cropland acidification rates and their drivers for the period 1985-2019 at 151 sites in a typical Chinese county with the combined nutrient and soil acidification model VSD+. VSD+ could well reproduce long-term changes in pH and in the BC concentrations of calcium, magnesium and potassium between 1985 and 2019 in non-calcareous soils. In paddy soils, the acidity production rate decreased from 1985 onwards, mainly driven by a pH-induced reduction in HCO3 leaching and N transformations. In upland soils, however, acidity production was mainly driven by N transformations and hardly changed over time. Crop BC removal by harvesting played a minor role in both paddy and upland soils, but its relative importance increased in paddy soils. The acidity input was partly neutralized by HCO3 input from fertilizers and manure, which decreased over time due to a change from ammonia bicarbonate to urea. Soil buffering by both BC and aluminium release decreased in paddy soils due to a reduction in net acidity production, while it stayed relatively constant in upland soils. We conclude that acidification management in paddy soils requires a focus on avoiding high HCO3 leaching whereas the management in upland soils should focus on balancing N with recycling organic manure and crop residues.

Interpretable machine learning based on CT-derived extracellular volume fraction to predict pathological grading of hepatocellular carcinoma.

PURPOSE: To develop a non-invasive auxiliary assessment method based on CT-derived extracellular volume (ECV) to predict the pathological grading (PG) of hepatocellular carcinoma (HCC). METHODS: The study retrospectively analyzed 238 patients who underwent HCC resection surgery between January 2013 and April 2023. Six machine learning algorithms were employed to construct predictive models for HCC PG: logistic regression, extreme gradient boosting, Light Gradient Boosting Machine (LightGBM), random forest, adaptive boosting, and Gaussian naive Bayes. Model performance was evaluated using receiver operating characteristic curve analysis, including area under the curve (AUC), sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and F1 score. Calibration plots were used for visual evaluation of model calibration. Clinical decision curve analysis was performed to assess potential clinical utility by calculating net benefit. RESULTS: 166 patients from Hospital A were allocated to the training set, while 72 patients from Hospital B (constituting 30.25% of the total sample) were assigned to the test set. The model achieved an AUC of 1.000 (95%CI: 1.000-1.000) in the training set and 0.927 (95%CI: 0.837-0.999) in the validation set, respectively. Ultimately, the model achieved an AUC of 0.909 (95%CI: 0.837-0.980) in the test set, with an accuracy of 0.778, sensitivity of 0.906, specificity of 0.789, negative predictive value of 0.556, and F1 score of 0.908. CONCLUSION: This study successfully developed and validated a non-invasive auxiliary assessment method based on CT-derived ECV to predict the HCC PG, providing important supplementary information for clinical decision-making.

Constrained control using novel nonlinear mapping for underactuated unmanned surface vehicles with unknown sideslip angle.

This paper addresses the problem of guidance and control for underactuated unmanned surface vehicles (USVs) with state constraints and input saturation, in support of enabling an underactuated USV to follow a parameterized curved path in the case of unknown sideslip angle and cross-tracking error constraint. First, a cross-tracking error constraint line-of-sight (LOS) guidance law with sideslip angle compensation is originally designed to guide an underactuated USV to convergence to the desired path within a time-varying cross-tracking error constraint. Second, a novel nonlinear mapping (NM) function is first constructed to map the heading and surge control subsystems with state constraints to unconstrained nonlinear systems, transforming the constrained control problem into the unconstrained control problem. Subsequently, adaptive fuzzy control laws are designed to achieve the control objectives for the USV using the new unconstrained nonlinear systems with unknown disturbance and input saturation. Then, a series of theoretical analyses using input-to-state stability theories are presented to prove the boundness of the tracking errors for the underactuated USV during path following. Finally, numerical results obtained using a physics-based simulation model are shown to reveal the effectiveness of the guidance and control algorithms.

Robotic versus open surgery for simultaneous resection of rectal cancer and liver metastases: a randomized controlled trial.

OBJECTIVE: This study aimed to compare the short-term and long-term outcomes between robotic-assisted simultaneous resection and open surgery in patients with rectal cancer and liver metastases. BACKGROUND: Open simultaneous resection of colorectal cancer and synchronous liver metastases is widely performed and the potential cure for eligible patients. However, the feasibility of robotic simultaneous resection of primary and secondary liver lesions has not been established as a treatment option for metastatic rectal cancer. PATIENTS AND METHODS: A single-center randomized controlled trial was conducted at a hospital in China. Enrolling patients were aged from 18 to 75 years and diagnosed with surgically resectable metastatic rectal cancer (distal extension to ≤15 cm from the anal margin). Patients selected for simultaneous resection were randomly assigned to have robotic or open surgery at a 1:1 ratio. The primary endpoint was the incidence rate of complications within 30 days after surgery. Secondary endpoints were bladder, sexual function, 3-year disease-free survival, and overall survival. RESULTS: A total of 171 patients were enrolled in this trial with 86 in the robotic group and 85 in the open group. As a result, patients in the robotic group demonstrated fewer complications within 30 days after surgery than those in the open group (31.4 vs. 57.6%, P =0.014) and no mortality seen in either group. Patients in the robotic group had less blood loss [mean (SD), 125.5 (38.3) vs. 211.6 (68.7) ml; P <0.001], faster bowel function recovery [mean (SD), 63.7 (27.4) vs. 93.8 (33.5) h P <0.001] and shorter hospital stay [mean (SD), 8.0 (2.2) vs. 10.7 (5.4) days; P <0.001] compared with those in the open group. The robotic group had a faster recovery of bladder and sexual function at 3 months after surgery than that of the open group. The 3-year disease-free survival rate (39.5 vs. 35.3%, P =0.739) and the 3-year overall survival rate (76.7 vs. 72.9%, P =0.712) were not statistically significant between the two groups. CONCLUSIONS: In our randomized clinical trial, robotic simultaneous resection treatment of patients with rectal cancer and liver metastases resulted in fewer surgical complications, and a faster recovery to those of open surgery. Oncological outcomes showed no significant difference between the two groups.

Study on the Manipulation Strategy of Metallic Microstructures Based on Electrochemical-Assisted Method.

Microcomponent manipulation (MCM) technology plays a decisive role in assembling complex systems at the micro- and nanoscale. However, the existing micromanipulation methods are difficult to widely apply in the manufacturing of microelectromechanical systems (MEMSs) due to the limited manipulation space and complex application objects, and the manipulation efficiency is relatively low, which makes it difficult to industrialize these micromanipulating systems. To solve the above problems, this paper proposes an efficient metal MCM strategy based on the electrochemical method. To verify the feasibility and repeatability of the strategy, the finite element model (FEM) incorporating the hydrodynamic and electrochemical theories is used to calculate the local stress distribution of the contact position during the dynamic pick-up process. Based on the simulation results, we defined the relationship between the parameters, such as the optimal manipulating position and angle for picking, transferring and releasing. The failure behaviors of pick-up are built to realize the efficient three-dimensional manipulation of microcopper wire of 300 µm. By establishing a theoretical model and experimental verification, it was concluded that the middle point was the best manipulating position when picking up the microcopper wire, the most efficient picking angle was between 45 and 60 degrees for the pipette, and the average time was 480 s in three sets of picking-release manipulation experiments. This paper provides an achievable idea for different types of micro-object manipulations and promotes the rapid application of micromanipulation techniques in MEMSs.

The m6A RNA Modification Quantity and the Prognostic Effect of Reader YTHDC2 in Colorectal Cancer.

Background: N6-methyladenosine (m6A) modification plays crucial roles in cancers. However, its alteration in colorectal cancer (CRC) is still poorly described. The purpose of this study is to explore the change of m6A modification and the function of m6A binding protein YTHDC2 in CRC. Methods: The global level of m6A modification was detected by mass spectrometry and dot blotting assay. The expression of YTHDC2 was investigated using The Cancer Genome Atlas and using real-time polymerase chain reaction (RT-qPCR), western blotting, and immunohistochemistry based on CRC tissues. Kaplan-Meier analysis and Cox proportional hazards regression were performed to analyze the prognostic value of YTHDC2. RNA immunoprecipitation (RIP)-seq and m6A immunoprecipitation (MeRIP)-seq were used to explore the direct targets of YTHDC2. Gene oncology (GO) and Gene Set Enrichment Analysis (GSEA) were used to explore the pathways that could be influenced by YTHDC2. Results: No significant difference was observed in the global level of m6A modification on total RNA or mRNA between CRC and adjacent nontumor tissues. We further found a significant decreasing of YTHDC2 in CRC tissues. Kaplan-Meier analysis indicated that lower expression of YTHDC2 was related to the worse disease-free survival and overall survival. In addition, lower expression of YTHDC2 was an independent worse prognostic factor in univariate and multivariate Cox regression analysis. Using YTHDC2-RIP-seq and MeRIP-seq, we identified that YTHDC2 could participate in several important biological signal pathways. Conclusions: In summary, this study suggested that the global level of m6A did not change in CRC and identified that lower YTHDC2 as a prognostic marker for worse survival of CRC.

Calculation of spatially explicit amounts and intervals of agricultural lime applications at county-level in China.

Liming is a long-established and widely used agricultural practice to ameliorate soil acidity and improve crop production. Sustainable liming strategies for regional applications require information on both lime requirements and liming intervals given land use and soil dependent acidification rates. We developed a method to optimize lime requirements and liming intervals at regional level. Lime requirements were based on soil pH buffering capacity and liming intervals were estimated by ongoing soil acidity production, derived from major cations and anions balances in cropland systems. About 66% of croplands in Qiyang required liming to raise soil pH to 6.5, with a total lime requirement of 2.4 × 105 t CaCO3, with an average rate of 2.4 t ha-1 for paddy soils and 2.6 t ha-1 for upland soils. The remaining 34% were mainly calcareous soils. Nutrient management practices and crop rotations, affecting N transformation and crop removal, were the main drivers controlling the spatial variation in total acid production in non-calcareous soils, on average contributing 73% and 25%, respectively. Under current soil acidification rates, 33% of Qiyang's croplands would need liming within 30 years after raising the soil pH to 6.5. Averaged liming interval was 20 years, and 6.8 t ha-1 would be required to maintain soil pH ranges between 5.5 and 6.5. Areas with high soil acidification risk were mostly located in the southeast of Qiyang.

Regorafenib in Refractory Metastatic Colorectal Cancer: A Multi-Center Retrospective Study.

Background: Regorafenib improves progression-free survival (PFS) and overall survival (OS) in patients with refractory metastatic colorectal cancer (mCRC). Here, we report the treatment patterns of regorafenib in the third- or late-line setting for mCRC in four centers in China. Patients and Methods: Patients with refractory mCRC in four centers in China administered regorafenib from February 1, 2018 to June 31, 2021 were enrolled. Patients were grouped into 3 cohorts, namely, the monotherapy (regorafenib alone), chemo (regorafenib plus chemotherapy), and immune [regorafenib plus anti-PD1 (programmed cell death 1) antibodies] groups. Demographic, clinical, survival and safety data were retrospectively analyzed. Results: A total of 177 patients were included in this study. Of them, 116 (65.5%) were treated with regorafenib alone, while 28 (15.9%) and 33 (18.6%) were administered regorafenib plus chemotherapy and anti-PD1 antibodies, respectively. The median followed-up time was 9.2 months. The disease control rate (DCR) was 40.7%. The median PFS (mPFS) was 2.43 months and the median OS (mOS) was 12.2 months. The immune group had longer median PFS (3.5 m vs. 2.2 m, p = 0.043) compared with the monotherapy group. Patients administered regorafenib plus chemotherapy had longer median OS (15.9 m vs. 8.4 m, p = 0.032) compared with the monotherapy group. Patients who began regorafenib treatment at 120 mg had longer median PFS and OS compared with those who began at 80 mg (PFS: 3.7 m vs. 2.0 m; p <0.001; OS: 13.4 m vs. 10.2 m; p = 0.005). Patients with a final dose of 120 mg had longer median PFS and OS compared with the 80 mg or less group (PFS: 5.0 m vs. 2.3 m; p = 0.045; OS: UR (unreach) vs. 10.9 m; p = 0.003). There were 87.0% (154/177) patients who experienced AEs. Three groups had similar rates of AEs (86.2% vs. 89.3% vs. 87.9%; p = 0.89). Conclusion: Patients administered regorafenib alone or regorafenib in combination with other agents were relieved to some extent, with a disease control rate of 40.7%. Regorafenib plus anti-PD1 antibodies showed better PFS, while regorafenib plus chemotherapy had the most benefit in OS. There was no significant difference among three groups in terms of AEs.

Morphological and histological analysis on the in vivo degradation of poly (propylene fumarate)/(calcium sulfate/ß-tricalcium phosphate).

Poly (propylene fumarate)/(Calcium sulfate/ß-tricalcium phosphate) (PPF/(CaSO(4)/ß-TCP)) is a kind of biodegradable composite designed for bone tissue engineering. The in vitro degradation behavior of this composite has been investigated in our previous study. The aim of this study was to investigate the effects of PPF molecular weight and CaSO(4)/ß-TCP molar ratio on the in vivo degradation of PPF/(CaSO(4)/ß-TCP) composite and the bone tissue response to PPF/(CaSO(4)/ß-TCP). Total 36 PPF/(CaSO(4)/ß-TCP) composite samples were implanted into 15.0 mm segmental defects in tibiae of 18 Japanese rabbits, harvested at 2, 4 and 8 weeks after the operation, and analyzed using radiographic and histological analysis to assess the in vivo degradation of the composites as well as tissue response to the implants. The in vivo degradation results show that all the samples maintained their original shape. Tissues penetrated into the pores which formed by the degradation of CaSO(4)/ß-TCP spheres near the surface of the composites. The rate of in vivo degradation and pore forming increased with a decrease in PPF molecular weight and an increase in CaSO(4)/ß-TCP molar ratio. No inflammatory reaction was observed after implantation, and the composites are capable of in situ pore forming. In particular, the pore forming rate can be adjusted by varying the composition of the composites. These results may indicate that PPF/(CaSO(4)/ß-TCP) is a promising osteogenic scaffold for its controllable degradation rate and excellent biocompatibility.

Modelling long-term impacts of fertilization and liming on soil acidification at Rothamsted experimental station.

Liming is widely used to reduce the impacts of soil acidification and optimize soil pH for agricultural production. Whether models can simulate the effect of liming on soil pH, and base saturation (BS), and thereby guide lime application, is still largely unknown. Long-term experimental data from a grassland (Park Grass, 1965-2012) and arable land (Sawyers Field, 1962-1972) at Rothamsted Research, UK, were thus used to assess the ability of the VSD+ model to simulate the effects of long-term fertilization and liming on soil acidification. The VSD+ model was capable of simulating observed soil pH and BS changes over time in the long-term liming experiments, except for a treatment in which sulphur (S) was added. Normalized Mean Absolute Errors (NMAE) and Normalized Root Mean Square Errors (NRMSE) of simulated and observed pH values, averaged over the observation periods varied between 0.02 and 0.08 (NMAE) and 0.01-0.05 (NRMSE). The acidity budget results for Park Grass suggest that nitrogen (N) transformations contributed most to acidity production, causing predominantly aluminium (Al) exchange in the topsoil (0-23 cm) followed by base cation (BC) release, but in the treatment with S addition, BC uptake had a nearly similar effect on acidity production. However, in Sawyers Field, the acidity budget suggested that BC uptake was the dominant cause of soil acidification, while the impacts of N transformations were limited. Liming was found to sufficiently replenish BC and decrease Al exchange in the topsoil layer. Overall, the VSD+ model can adequately reconstruct the impacts of fertilizer and liming applications on acid neutralizing processes and related soil pH and BC changes at the soil exchange complex.

Health-related lifestyle behaviors among male and female rural-to-urban migrant workers in Shanghai, China.

BACKGROUND: Lifestyle behaviors significantly impact health, yet remain poorly defined in Chinese rural-to-urban migrants. METHODS: In a cross-sectional study of health-related behaviors of 5484 rural-to-urban migrants who had worked in Shanghai for at least six months, we assessed the contribution of demographics and physical and mental health to lifestyle behaviors in male and female participants by multiple stepwise cumulative odds logistic regression. RESULTS: Respondents were 51.3% male. 9.9% exhibited abnormal blood pressure; 27.0% were overweight or obese; 11.2% reported abnormal mental health; 36.9% reported healthy lifestyle. Multiple stepwise cumulative odds logistic regression indicated that men working in manufacturing reported less unhealthy lifestyle than those in hospitality (cumulative odds ratio (COR) = 1.806, 95%CI 1.275-2.559) or recreation/leisure (COR = 3.248, 95%CI 2.379-4.435); and women working in manufacturing and construction reported less unhealthy lifestyle than those in all other sectors. Unhealthy lifestyle was associated with small workplaces for men (COR = 1.422, 95%CI 1.154-1.752), working more than 8 or 11 hours per day for women and men, respectively, and earning over 3500 RMB in women (COR = 1.618, 95%CI 1.137-2.303). Single women and women who had previously resided in three or more cities were more likely to report unhealthy lifestyle (COR = 2.023, 95%CI 1.664-2.461, and COR = 1.311, 95%CI 1.072-1.602, respectively). Abnormal mental status was also correlated with unhealthy lifestyle in men (COR = 3.105, 95%CI 2.454-3.930) and women (COR = 2.566, 95%CI 2.024-3.252). CONCLUSIONS: There were different risk factors of unhealthy lifestyle score in male and female rural-to-urban migrants, especially in number of cities experienced, salary, marital status, work place scale. Several demographic groups: employment sectors (e.g. hospitality and recreation/leisure), working conditions (e.g. long hours) and abnormal mental status were associated with unhealthy lifestyle behaviors in Chinese rural-to-urban migrants, and health interventions should be targeted to these groups.