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Abstract Introduction Aneurysmal subarachnoid haemorrhage (aSAH) is a condition with significant morbidity and mortality. Traditional markers of aSAH have established their utility in the prediction of aSAH outcomes while frailty markers have been validated in other surgical specialties. We aimed to compare the predictive value of frailty indices and markers of sarcopaenia and osteopaenia, against the traditional markers for aSAH outcomes. Methods An observational study in a tertiary neurosurgical unit on 51 consecutive patients with ruptured aSAH was performed. The best performing marker in predicting the modified Rankin scale (mRS) on discharge was selected and an appropriate threshold for the definition of frail and non-frail was derived. We compared various frailty indices (modified frailty index 11, and 5, and the National Surgical Quality Improvement Program score [NSQIP]) and markers of sarcopaenia and osteopaenia (temporalis [TMT] and zygoma thickness), against traditional markers (age, World Federation of Neurological Surgery and modified Fisher scale [MFS]) for aSAH outcomes. Univariable and multivariable analysis was then performed for various inpatient and long-term outcomes. Results TMT was the best performing marker in our cohort with an AUC of 0.82, Somers’ D statistic of 0.63 and Tau statistic 0.25. Of the frailty scores, the NSQIP performed the best (AUC 0.69), at levels comparable to traditional markers of aSAH, such as MFS (AUC 0.68). The threshold of 5.5 mm in TMT thickness was found to have a specificity of 0.93, sensitivity of 0.51, positive predictive value of 0.95 and negative predictive value of 0.42. After multivariate analysis, patients with TMT ≥ 5.5 mm (defined as non-frail), were less likely to experience delayed cerebral ischaemia (OR 0.11 [0.01 – 0.93], p = 0.042), any complications (OR 0.20 [0.06 – 0.069], p = 0.011), and had a larger proportion of favourable mRS on discharge (95.0% vs. 58.1%, p = 0.024) and at 3-months (95.0% vs. 64.5%, p = 0.048). However, the gap between unfavourable and favourable mRS was insignificant at the comparison of 1-year outcomes. Conclusion TMT, as a marker of sarcopaenia, correlated well with the presenting status, and outcomes of aSAH. Frailty, as defined by NSQIP, performed at levels equivalent to aSAH scores of clinical relevance, suggesting that, in patients presenting with acute brain injury, both non-neurological and neurological factors were complementary in the determination of eventual clinical outcomes. Further validation of these markers, in addition to exploration of other relevant frailty indices, may help to better prognosticate aSAH outcomes and allow for a precision medicine approach to decision making and optimization of best outcomes.

Abstract To investigate the urodynamic study (UDS) result in pediatric patients suffering from spastic cerebral palsy (CP). Medical records of patients diagnosed CP having pre-operative UDS results underwent selective dorsal rhizotomy (SDR) from Jan. 2020 to May. 2021 were retrospectively reviewed. Fifty-seven cases diagnosed spastic CP were included in the study (mean age, 6.73 ± 2.84 years), among which, 46 were ambulatory and 11 non-ambulatory. Average gross motor function measure-66 (GMFM-66) score was 62.16 ± 11.39. Reduced bladder capacity was seen in 49.12% of these cases and cases with lower GMFM-66 score possessed a higher incidence rate of having low bladder capacity (p

Abstract Objective To explore the feasibility and clinical efficacy of a modified medial collateral ligament indentation technique in total knee arthroplasty (TKA) with severe type II valgus deformity. Methods Consecutive patients with Krackow type II valgus deformity >20° who underwent a primary unilateral TKA between May 2008 and June 2017 were studied retrospectively. A medial collateral ligament indentation technique was performed in 20 patients (MCLI group), and 23 patients received the routine lateral structures release technique (LSR group). Radiological parameters, such as the valgus angle (VA), and functional outcomes including the use of constraint implants, Knee Society Score (KSS), Knee Society Function score (KSF), and thickness of the polyethylene insert were compared between the two groups. Results A total of 43 consecutive patients had a minimum 2‐year follow‐up. The preoperative VA was comparable between the MCLI (23.5° ± 5.8°) and LSR groups (21.3° ± 3.2°, P = 0.134), as was the postoperative VA (1.1° ± 2.1° and 2.5° ± 3.0°, respectively, P = 0.084). The mean KSS and KSF scores in the MCLI group were 30.2 ± 4.8 and 38.8 ± 4.8, respectively, before surgery, and they increased to 91.3 ± 2.6 and 86.5 ± 2.4 at the last follow‐up. The scores in the LSR group were 31.5 ± 7.5 and 36.5 ± 7.8 before surgery and 92.4 ± 3.5 and 88.5 ± 3.6 at the last follow‐up. While no statistically significant differences in pre‐ or postoperative functional scores were found between the two groups, the MCLI group had thinner polyethylene inserts (9.5 ± 1.1 mm vs 12.9 ± 1.5 mm) and less use of constrained condylar inserts (15% vs 69.6%). During follow‐up, the MCLI group had fewer complications. Conclusion A modified MCLI technique can achieve good outcomes in TKA with type II valgus deformity of >20°. It can maintain a normal joint line level, reduce the use of constrained condylar knee prostheses, and is a reliable choice for severe genu valgum.

This manuscript introduces an improved Cuckoo Search (CS) algorithm, known as BASCS, designed to address the inherent limitations of CS, including insufficient search space coverage, premature convergence, low search accuracy, and slow search speed. The proposed improvements encompass four main areas: the integration of tent chaotic mapping and random migration in population initialization to reduce the impact of random errors, the guidance of Levy flight by the directional determination strategy of the Beetle Antennae Search (BAS) algorithm during the global search phase to improve search accuracy and convergence speed, the adoption of the Sine Cosine Algorithm for local exploitation in later iterations to enhance local optimization and accuracy, and the adaptive adjustment of the step-size factor and elimination probability throughout the iterative process to convergence. The performance of BASCS is validated through ablation experiments on 10 benchmark functions, comparative experiments with the original CS and its four variants, and application to a robot path planning problem. The results demonstrate that BASCS achieves higher convergence accuracy and exhibits faster convergence speed and superior practical applicability compared to other algorithms. [ABSTRACT FROM AUTHOR]

AbstractBackground and ObjectiveMethodsResultsConclusionsAsthma is a heterogeneous respiratory disease characterized by airway hyper-responsiveness and reversible airflow blockage. There is ongoing debate about the impact of vitamin D on asthma. This research is focused on investigating the correlation between serum levels of 25-hydroxyvitamin D and asthma.This cross-sectional study comprised 22,708 eligible participants. Data on asthma and serum 25-hydroxyvitamin D levels from the National Health and Nutrition Examination Survey (NHANES) 2011–2018 were analyzed. Serum 25-hydroxyvitamin D levels were the main factor, with the presence of asthma as the outcome variable. Weighted logistic regression was utilized to investigate the relationship between serum levels of 25-hydroxyvitamin D and asthma, while accounting for factors such as age, gender, race, length of time in US, annual family income, education level, high-density lipoprotein, low-density lipoprotein, triglycerides, and cholesterol.Upon adjusting all variables in model III, epi-25-hydroxyvitamin D3 displayed a negative correlation with current asthma at the lower quartile Q1 (0.784, [0.697 to 0.922]), Q2 (0.841, [0.729 to 0.946]), Q3 (0.396, [0.240 to 0.653]) when compared to the highest quartile Q4 level. However, no significant difference was observed between asthma and 25-hydroxyvitamin D2, as well as 25-hydroxyvitamin D3.In the U.S. population, elevated levels of epi-25-hydroxyvitamin D3 are correlated with an increased risk of developing existing asthma. However, it is important to interpret this finding carefully given the constraints of cross-sectional studies. [ABSTRACT FROM AUTHOR]

Objective To evaluate the short-term efficacy and safety of two Janus kinase (JAK) 1 inhibitors, upadacitinib and abrocitinib, in the treatment of atopic dermatitis of the head and neck. Methods This study retrospectively analyzed the clinical data of patients with atopic dermatitis of the head and neck who received upadacitinib and abrocitinib in the Department of Dermatology, the First Affiliated Hospital of Soochow University from January 2022 to June 2023. At 0,2,4,8, and 12 weeks after treatment, clinical symptoms and itching of patients were scored using the eczema area and severity index (EASI),investigator's global assessment (IGA), visual analogue scale (VAS) itch score, and the body surface area (BSA), to evaluate the efficacy and safety of treatment. Meanwhile, the two treatments were compared in terms of satisfactory efficacy. Results A total of 33 patients were included in the study, including 19 in the upadacitinib group and 14 in the abrocitinib group. At 12 weeks after treatment, EASI, VAS, IGA and BSA scores in both the upadacitinib and abrocitinib groups showed significant declines. Furthermore, there was no significant difference between the upadacitinib and abrocitinib groups in the percentage of patients achieving satisfactory outcomes. In terms of adverse reactions, 7 patients in the upadacitinib group and 5 patients in the abrocitinib group had adverse reactions, and the most common adverse reactions were acne and gastrointestinal discomfort respectively. Conclusion The results of this study indicate that JAK1 inhibitors upadacitinib and abrocitinib have good short-term efficacy and high safety in the treatment of atopic dermatitis of the head and neck. [ABSTRACT FROM AUTHOR]

Atmospheric CO2 concentration is elevated globally, which has "CO2 fertilization effects" and potentially improves plant photosynthesis, yield, and productivity. Despite the beneficial effect of CO2 fertilization being modulated by vapor pressure deficit (VPD), the underlying mechanism is highly uncertain. In the present study, the potential roles of hormones in determining CO2 fertilization effects under contrasting high and low VPD conditions were investigated by integrated physiological and transcriptomic analyses. Beneficial CO2 fertilization effects were offset under high VPD conditions and were constrained by plant water stress and photosynthetic CO2 utilization. High VPD induced a large passive water driving force, which disrupted the water balance and consequently caused plant water deficit. Leaf water potential, turgor pressure, and hydraulic conductance declined under high VPD stress. The physiological evidence combined with transcriptomic analyses demonstrated that abscisic acid (ABA) and jasmonic acid (JA) potentially acted as drought-signaling molecules in response to high VPD stress. Increased foliar ABA and JA content triggered stomatal closure to prevent excessive water loss under high VPD stress, which simultaneously increased the diffusion resistance for CO2 uptake from atmosphere to leaf intercellular space. High VPD also significantly increased mesophyll resistance for CO2 transport from stomatal cavity to fixation site inside chloroplast. The chloroplast "sink" CO2 availability was constrained by stomatal and mesophyll resistance under high VPD stress, despite the atmospheric "source" CO2 concentration being elevated. Thus, ABA- and JA-mediated drought-resistant mechanisms potentially modified the beneficial effect of CO2 fertilization on photosynthesis, plant growth, and yield productivity. This study provides valuable information for improving the utilization efficiency of CO2 fertilization and a better understanding of the physiological processes. [ABSTRACT FROM AUTHOR]

An accurate model of the Zenith Tropospheric Delay (ZTD) plays a crucial role in Global Navigation Satellite System (GNSS) precise positioning, water vapor retrieval, and meteorological research. Current empirical models (such as the GPT3 model) can only reflect the approximate change trend of ZTD but cannot accurately reflect nonlinear changes such as rapid fluctuations in ZTD. In recent years, the application of machine learning methods in the modeling and prediction of ZTD has gained prominence, yielding commendable results. Utilizing the ZTD products from 53 International GNSS Service (IGS) stations in Europe during the year 2021 as a foundational dataset, a Generalized Regression Neural Network (GRNN) is employed to model IGS ZTD while considering spatiotemporal factors and its association with GPT3 ZTD. This endeavor culminates in the development of a refined GRNN model. To verify the performance of the model, the prediction results are compared with two other ZTD values. One is obtained based on the European Centre for Medium-Range Weather Forecasts Reanalysis 5 (ERA5) data, and the other is obtained by the GPT3 model. The results show that the bias of the GRNN refined model is almost 0 mm, and the average Root-Mean-Square Error (RMSE) and Mean Absolute Error (MAE) are 18.33 mm and 14.08 mm, respectively. Compared with ERA5 ZTD and GPT3 ZTD, the RMSE of GRNN ZTD has decreased by 19.5% and 63.4%, respectively, and the MAE of GRNN ZTD has decreased by 24.8% and 67.1%. Compared with the other two models, the GRNN refined model has better performance in reflecting the rapid fluctuations of ZTD. In addition, also discussed is the impact of spatial factors and time factors on modeling. The findings indicate that modeling accuracy within the central region of the modeling area surpasses that at the periphery by approximately 17.8%. The period from June to October is associated with the lowest accuracy, whereas the optimal accuracy is typically observed from January to April. The most substantial differences in accuracy were observed at station OP71 (Paris, France), with the highest accuracy recorded (9.51 mm) in April and the lowest (24.00 mm) in September.

To verify the dynamic model of a paddy-field laser grader and solve the problem of the unstable high-speed operation of the grader, a method for measuring the absolute pose parameters of a moving rigid body using a monocular camera is proposed. The proposed method does not require calibration beforehand. Using more than six non-coplanar control points symmetrically arranged in the rigid-body and world coordinate systems, the matrices of rotation and translation between the camera and two coordinate systems are obtained and the absolute pose of the rigid body is measured. In this paper, formulas of the absolute pose measurement of a moving rigid body are deduced systematically and the complete implementation is presented. Position and attitude measurement experiments carried out on a three-axis precision turntable show that the average absolute error in the attitude angle of a moving rigid body measured by an uncalibrated camera at different positions changes by no more than 0.2 degrees. An analysis of the three-dimensional coordinate errors of the centroid of a moving rigid body shows little deviation in measurements taken at the three camera positions, with the maximum deviation of the average absolute error being 0.53 cm and the maximum deviation of the standard deviation being 0.66 cm. The proposed method can measure the absolute pose of a rigid body and is insensitive to the position of the camera in the measurement process. This work thus provides guidance for the repeated measurement of the absolute pose of a moving rigid body using a monocular camera.

Background: Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive form of sarcomas with a poor prognosis and limited treatment options. Therefore, new therapeutic targets are urgently needed to identify novel drugs. Methods: Based on the Gene Expression Omnibus database, an integrated analysis was performed to identify differentially expressed genes (DEGs) in MPNSTs compared to neurofibromas (NFs). Then functional enrichment analyses, protein-protein interaction (PPI) network construction, and hub gene selection were conducted. We explored DEG-guided repurposable drugs to treat MPNST based on the Library of Integrated Network-Based Cellular Signatures (LINCS) database. Furthermore, the binding affinity between predicted drug candidates and the MPNST-associated hub gene was calculated using molecular docking. Results: We identified 89 DEGs in common with all three MPNSTs datasets. In the PPI networks, twist family bHLH transcription factor 1 (Twist1) with higher node degrees was further evaluated as a therapeutic target. Cytochalasin-d, cabozantinib, everolimus, refametinib, and BGT-226 were extracted from the LINCS database, which showed lower normalized connectivity scores (–1.88, –1.81, –1.78, –1.76, and –1.72, respectively) and was considered as drug candidates. In addition, the results of molecular docking between the five drugs and Twist1 showed a binding affinity of –6.61, –7.03, –7.73, –3.94, and –7.07 kcal/mol, respectively. Conclusions: Overall, our results describe the importance of Twist1 in MPNST pathogenesis. Everolimus was also found to be a potential therapeutic drug for MPNSTs.

Hypocotyl length is a critical determinant for the efficiency of mechanical harvesting in pakchoi production, but the knowledge on the molecular regulation of hypocotyl growth is very limited. Here, we report a spontaneous mutant of pakchoi, lhy7.1, and identified its characteristics. We found that it has an elongated hypocotyl phenotype compared to the wild type caused by the longitudinal growth of hypocotyl cells. Different light quality treatments, transcriptome, and proteomic analyses were performed to reveal the molecular mechanisms of hypocotyl elongation. The data showed that the hypocotyl length of lhy7.1 was significantly longer than that of WT under red, blue, and white lights but there was no significant difference under dark conditions. Furthermore, we used transcriptome and label-free proteome analyses to investigate differences in gene and protein expression levels between lhy7.1 and WT. At the transcript level, 4568 differentially expressed genes (DEGs) were identified, which were mainly enriched in “plant hormone signal transduction”, “photosynthesis”, “photosynthesis–antenna proteins”, and “carbon fixation in photosynthetic organisms” pathways. At the protein level, 1007 differentially expressed proteins (DEPs) were identified and were mainly enriched in photosynthesis-related pathways. The comprehensive transcriptome and proteome analyses revealed a regulatory network of hypocotyl elongation involving plant hormone signal transduction and photosynthesis-related pathways. The findings of this study help elucidate the regulatory mechanisms of hypocotyl elongation in lhy7.1.

Indoor positioning using smartphones has garnered significant research attention. Geomagnetic and sensor data offer convenient methods for achieving this goal. However, conventional geomagnetic indoor positioning encounters several limitations, including low spatial resolution, poor accuracy, and stability issues. To address these challenges, we propose a fusion positioning approach. This approach integrates geomagnetic data, light intensity measurements, and inertial navigation data, utilizing a hierarchical optimization strategy. We employ a Tent-ASO-BP model that enhances the traditional Back Propagation (BP) algorithm through the integration of chaos mapping and Atom Search Optimization (ASO). In the offline phase, we construct a dual-resolution fingerprint database using Radial Basis Function (RBF) interpolation. This database amalgamates geomagnetic and light intensity data. The fused positioning results are obtained via the first layer of the Tent-ASO-BP model. We add a second Tent-ASO-BP layer and use an improved Pedestrian Dead Reckoning (PDR) method to derive the walking trajectory from smartphone sensors. In PDR, we apply the Biased Kalman Filter–Wavelet Transform (BKF-WT) for optimal heading estimation and set a time threshold to mitigate the effects of false peaks and valleys. The second-layer model combines geomagnetic and light intensity fusion coordinates with PDR coordinates. The experimental results demonstrate that our proposed positioning method not only effectively reduces positioning errors but also improves robustness across different application scenarios.

Abstract Background This study aimed to explore the clinical features of gout in adult patients with glycogen storage disease type Ia (GSD Ia). Methods Ninety-five adult patients with GSD Ia admitted to Peking Union Medical College Hospital were retrospectively analysed. A clinical diagnosis of GSD Ia was confirmed in all patients through gene sequencing. All patients had hyperuricaemia; 31 patients complicated with gout were enrolled, and 64 adult GSD Ia patients with asymptomatic hyperuricaemia were selected as a control group during the same period. Clinical characteristics were analysed and compared between the two groups. Results Thirty-one of the 95 patients had complications of gout (median age, 25 years; 11 (35.5%) females). All 31 patients had hepatomegaly, abnormal liver function, fasting hypoglycaemia, hyperuricaemia, hyperlipaemia, and hyperlacticaemia. A protuberant abdomen, growth retardation, recurrent epistaxis, and diarrhoea were the most common clinical manifestations. Among these 31 patients, 10 patients (32.3%) had gout as the presenting manifestation and were diagnosed with GSD Ia at a median time of 5 years (range, 1–14) after the first gout flare. The median age of gout onset was 18 years (range, 10–29). Fifteen of the 31 GSD Ia-related gout patients were complicated with gouty tophi, which has an average incidence time of 2 years after the first gouty flare. The mean value of the maximum serum uric acid (SUA) was 800.5 μmol/L (range, 468–1068). The incidence of gout in adult GSD Ia patients was significantly associated with the initial age of regular treatment with raw corn starch, the proportion of urate-lowering therapy initiated during the asymptomatic hyperuricaemic stage, maximum SUA level, and mean cholesterol level. Conclusions Determination of GSD Ia should be performed for young-onset gout patients with an early occurrence of gouty tophi, especially in patients with hepatomegaly, recurrent hypoglycaemia, or growth retardation. Early detection and long-term regulatory management of hyperuricaemia, in addition to early raw corn starch and lifestyle intervention, should be emphasized for GSD Ia patients in order to maintain good metabolic control. Trial registration Retrospectively registered.

Abstract Human oral bioavailability (HOB) is a key factor in determining the fate of new drugs in clinical trials. HOB is conventionally measured using expensive and time-consuming experimental tests. The use of computational models to evaluate HOB before the synthesis of new drugs will be beneficial to the drug development process. In this study, a total of 1588 drug molecules with HOB data were collected from the literature for the development of a classifying model that uses the consensus predictions of five random forest models. The consensus model shows excellent prediction accuracies on two independent test sets with two cutoffs of 20% and 50% for classification of molecules. The analysis of the importance of the input variables allowed the identification of the main molecular descriptors that affect the HOB class value. The model is available as a web server at www.icdrug.com/ICDrug/ADMET for quick assessment of oral bioavailability for small molecules. The results from this study provide an accurate and easy-to-use tool for screening of drug candidates based on HOB, which may be used to reduce the risk of failure in late stage of drug development. Graphical Abstract

Objective To evaluate the proprioceptive and clinical function of the knee joint after anterior cruciate ligament reconstruction (ACLR) with various amounts of remnant preserved with as few confounding factors as possible. Methods This retrospective study included 46 patients who underwent ACLR with remnant preservation between March 2013 and February 2019. These patients had less than 6 months injury‐to‐surgery interval and no concomitant injuries. The researchers divided these subjects into two groups based on the length of the remnant preserved after ACLR, with group A defined as having more than 1/3 of the original length preserved and group B defined as less than 1/3 of the original length preserved. Clinical scores were obtained using the Lysholm knee scoring scale and the Tegner activity scale. The Lysholm score was calculated preoperatively, at 3, 6, and 12 months postoperatively, and at the last follow up. The Tegner score was calculated preoperatively, at 12 months postoperatively and at the last follow up. Anterior laxity was measured using the KT2000 arthrometer preoperatively and at 12 months postoperatively. Proprioceptive function was evaluated through reproduction of passive positioning (RPP) and threshold to detection of passive motion (TDPM). Both RPP and TDPM were measured at the angle of 15° at 3, 6, and 12 months postoperatively. Unpaired t‐tests were performed to investigate the difference in each parameters between the two groups. Results In the present study, 20 patients were classified into group A and 26 into group B. All patients were followed up for an average of 34.70 ± 12.79 months. All 46 patients were satisfied with the outcome of the surgery and no complications were reported at the end of the study. No significant differences were found between the two groups in terms of the Lysholm score and anterior laxity by KT2000 at all time points. The Tegner score was significantly higher in group A at 12 months postoperatively and at the final follow‐up. In addition, group A's RPP was significantly better than that of group B's when tested at the angles of 15° and 30° at 3 months postoperatively, and at the angle of 15° at 6 months postoperatively. Group A's TDPM was also significantly better than that of group B's at all three tested angles at 3 months postoperatively, and at the angle of 15° at 6 months postoperatively. Conclusion Patients with ACLR with more than 1/3 of the original length preserved demonstrated a higher activity level 12 months postoperatively and better proprioceptive function at 15° of extension at 3 and 6 months postoperatively.

Objectives: In response to the COVID-19 pandemic, primary care swiftly transformed and re-established patient flow in clinics to red, orange, and green zones based on a set of screening criteria. To further manage the influx of suspected COVID-19 patients and their needs safely, a list of surveillance audit criteria was developed to ensure good infection control standards. Methods: The infection control team prepared the surveillance audit criteria based on recommended CDC/WHO guidelines for pandemic preparedness. These criteria were contextualized to the primary-care polyclinic setting. The surveillance audit criteria were grouped according to their category: screening, triage, early recognition and source control, inventory management of personal protective equipment (PPE), infection control measures in the red zone, precautionary measures during collection of nasopharyngeal swabs and environmental cleaning and disinfection for premises in the red, orange, and green zones, respectively. The infection control liaison nurses in each polyclinic were trained to use the checklist to ensure consistency in interpretation of the criteria. Results: Surveillance audits were conducted biweekly in the first 3 months then monthly once the compliance rate was steady at 90%–100% for all categories. The overall average compliance rate since commencing in March 2020 for all polyclinics was sustained at 90%–100%. Common findings included inappropriate use of PPE (eg, self-contamination during removal of gown or wrong sequence of doffing), inadequate ventilation, and inadequate cleaning processes. All findings were corrected immediately, and staff education was provided. Conclusions: Primary care plays an important role during a pandemic. It is essential that both patients and healthcare workers in the primary care setting are protected from infection risk during a pandemic. Having a good surveillance audit process helps ensure that primary care services can continue for the general population. Surveillance is an essential component of the health system’s response to a pandemic.

Background Acanthopanacis Cortex (AC) is a valuable Chinese medicine, which exerts beneficial effects on anti-fatigue, anti-stress, and inflammatory modulation in the periphery. However, the central nervous system (CNS) function of AC has not been clearly illustrated. As communication between the peripheral immune system and the CNS converges, it promotes a heightened neuroinflammatory environment that contributes to depression. We investigated the effect of AC against depression through neuroinflammatory modulation. Methods Network pharmacology was used to screen for target compounds and pathways. Mice with CMS-induced depression were used to evaluate the efficacy of AC against depression. Behavioral studies and detection of neurotransmitters, neurotrophic factors, and pro-inflammatory cytokines were performed. The IL-17 signaling cascade was involved to further investigate the underlying mechanism of AC against depression. Results Twenty-five components were screened by network pharmacology and the IL-17 mediated signaling pathway was associated with the antidepressant action of AC. This herb had a beneficial effect on CMS-induced depressive mice, including improvements in depressive behavior, modulation of neurotransmitter levels, neurotrophic factors, and pro-inflammatory cytokines. Conclusions Our results revealed that AC exhibits effects on anti-depression and one of the mechanisms was mediated by neuroinflammatory modulation.

The film condensation of steam is very common in several industrial areas, such as condensers in power plants, seawater desalination, and air-conditioning systems. In some studies, the non-condensable gas and liquid film are overlooked for the sake of simplicity. To provide an integral computational scheme, in the present study, the film condensation of steam in the presence of non-condensable gas on a vertical plate has been simulated using a two-dimensional CFD model combining a wall condensation model and volume of fluid (VOF) model. After verification, the proposed computational scheme is used to simulate the steam condensation process, with the mass fractions of non-condensable gas varying from 5% to 45%. The results indicate that the concentration of non-condensable gas in the boundary layer decreases gradually with the condensation process, resulting in a decline in the synergy between temperature and velocity field. It can also be found that the fluctuation of the liquid film can influence the concentration distribution of the non-condensable gas layer. For cases with high concentrations of steam, the thermal resistance of liquid film can reach more than 20% of the total thermal resistance, which should not be ignored.

Various light spectra, especially red (RL) and blue light (BL), have great effects on physiological processes and growth of plants. Previously, we revealed that the plant photomorphogenesis and photosynthesis of sweet pepper was significantly altered under BL or mixed RL and BL. The present study aimed to elucidate how mixed RL and BL influences plant photosynthesis during photomorphogenesis. We examined the growth, plant morphology, photosynthetic response of sweet pepper seedlings under monochromatic RL, BL, different ratios of mixed RL and BL (9R1B, 6R1B, 3R1B, 1R1B, 1R3B) with the same photosynthetic photon flux density of 300 μmol·m-2·s-1. White light (WL) were used as a control. The findings showed that the elongation of hypocotyl and first internode as well as leaf expansion were all stimulated by RL, while significantly restrained by BL compared with WL. Conversely, the leaf development, biomass accumulation and photosynthetic properties were inhibited by RL but promoted by BL. Additionally, compared with WL and other treatments, 3R1B could significantly improve the net photosynthetic rate, gas exchange, photosynthetic electron transport capacity, photochemical efficiency, shoot and root biomass accumulation. Furthermore, seedlings grew robustly and exhibited the greatest value of seedling index when exposed to this treatment. Overall, these results suggested that pepper seedlings grown under 3R1B performed better, possibly due to the more balanced light spectrum. It was more conducive to improve the plant photomorphogenesis and photosynthesis of sweet pepper, and a higher biomass accumulation and energy utilization efficiency could be achieved simultaneously under this mixed light spectrum.

Polymethyl methacrylate (PMMA) bone cement (PBC) is commonly used in orthopaedic surgery. However, polymerization volumetric shrinkage, exothermic injury, and low bioactivity prevent PBC from being an ideal material. The developed expandable P(MMA-AA-St) well overcomes the volumetric shrinkage of PBC. However, its biomechanical properties are unsatisfactory. Herein, graphene oxide (GO), a hydrophilic material with favourable biomechanics and osteogenic capability, was added to P(MMA-AA-St) to optimize its biomechanics and bioactivity. The GO-modified self-expandable P(MMA-AA-St)-GO nanocomposite (PGBCs) exhibited outstanding compressive strength (>70 ​MPa), water absorption, and volume expansion, as well as a longer handling time and a reduced setting temperature. The cytocompatibility of PGBCs was superior to that of PBC, as demonstrated by CCK-8 assay, live-dead cell staining, and flow cytometry. In addition, better osteoblast attachment was observed, which could be attributed to the effects of GO. The improved level of osteogenic gene and protein expression further illustrated the improved cell-material interactions between osteoblasts and PGBCs. The results of an in vivo study performed by filling bone defects in the femoral condyles of rabbits with PGBCs demonstrated promising intraoperative handling properties and convenient implantation. Blood testing and histological staining demonstrated satisfactory in vivo biosafety. Furthermore, bone morphological and microarchitecture analyses using bone tissue staining and micro-CT scanning revealed better bone-PGBCs contact and osteogenic capability. The results of this study indicate that GO modification improved the physiochemical properties, cytocompatibility, and osteogenic capability of P(MMA-AA-St) and overcame the drawbacks of PBC, allowing its material derivatives to serve as effective implantable biomaterials.

Chrysanthemi Indici Flos (CIF) is the inflorescence of Chrysanthemum indicum L., which exists in various shades of yellow and has pharmacologically active constituents. It is widely used for medicinal purposes in China, Japan, and South Korea to treat inflammatory diseases. Its external color is usually used to judge its internal quality in trade; however, the correlation between its color and chemical constituents is unknown. Here, we simultaneously determined five phenylpropanoids (neochlorogenic acid, chlorogenic acid, and isochlorogenic acids A, B, and C) and four flavonoids (linarin, luteolin, apigenin, and acacetin) of 70 CIF germplasms using a newly established UPLC method; furthermore, we measured their color parameters (L*, a*, and b*) using a spectrophotometer. Our results showed considerable variations in the bioactive constituent contents and color parameters of CIF. The content of the five phenylpropanoids and the relative correlation degree γi of the nine constituents were positively correlated with color parameters, which could be rapidly predicted based on L* and/or b*. Moreover, we screened out a high-quality germplasm with a high linarin content and bright colors using the hierarchical clustering method. Our results provide comprehensive insight into CIF's quality evaluation process, particularly the methods for procuring high-quality medicinal materials and breeding by color.

Purpose: The formation mechanism of spinal extradural arachnoid cysts (SEACs) remains unclear. There are several hypotheses for the formation of SEACs, but none of them can fully explain its pathological findings and surgical procedures. In this study, we retrospectively analyzed the cases of SEACs, aiming to clarify the formation mechanism of SEACs. In addition, we summarize a concise method for locating dural defects preoperatively and formulate a putative explanation of this method. Methods: The clinical data of 14 patients with SEACs underwent surgery in our hospital from January 2017 to December 2021 were retrospectively analyzed. Results: Fourteen patients were identified during the study period. The cysts all spanned the T12/L1 segment, and dural defects were also located at the T12/L1 level (2 cases not recorded) as well as the middle or the upper-middle level of the cysts. Nine cases were treated with total cyst excision, 2 cases were treated with dural defect closure only, and 3 cases were treated with total cyst excision and dural defect closure. Histopathological examination demonstrated that the cyst wall contained both the arachnoid epithelial and compact fibrous connective tissue. The symptoms were relieved in all patients, and no recurrence was observed. Conclusions: According to intraoperative and pathological findings, the dural outer layer cyst (DOLC) is a more reasonable hypothesis about SEACs formation. When CT myelography or cinematic MRI cannot determine the location of the dural defect preoperatively, it can be located according to the middle level of the SEACs with high accuracy.

Purpose: Nanoparticles (NPs) of the polydopamine (PDA)-based,loaded with temozolomide (TMZ) and conjugated with Pep-1 (Peptide-1) as a feasible nano-drug delivery system were constructed and utilized for chemotherapy (CT) and photothermal therapy (PTT) of glioblastoma (GBM).Method: PDA NPs were synthesized from dopamine (DA) hydrochloride and reacted with TMZ to obtain the PDA-TMZ NPs and then the PDA NPs and the PDA-TMZ NPs were conjugated and modified by Pep-1 to obtain the Pep-1@PDA NPs and Pep-1@PDA-TMZ NPs via the Schiff base reaction (SBR), respectively.Their dimensions, charge, and shape were characterized by dynamic light scattering (DLS) and scanning electron microscope (SEM). The assembly of TMZ was verified by Fourier-transform infrared spectroscopy (FT-IR) and ultraviolet and visible spectroscopy (UV-Vis). The biostability of both the nanocarrier and the synthetic NPs were validated using water and fetal bovine serum (FBS). The antitumor activities of the PDA-TMZ NPs and Pep-1@PDA-TMZ NPs were verified in U87 cells and tumor-bearing nude mice.Results: The prepared PDA NPs, PDA-TMZ NPs, Pep-1@PDA NPs, and Pep-1@PDA-TMZ NPs were regular and spherical, with dimension of approximately 122, 131, 136, and 140 nm, respectively. The synthetic nanoparticles possessed good dispersity, stability,solubility, and biocompatibility. No obvious toxic side effects were observed, and the loading rate of TMZ was approximately 50%.In vitro research indicated that the inhibition ratio of the Pep-1@PDA-TMZ NPs combined with 808 nm laser was approximately 94% for U87 cells and in vivo research was approximately 77.13%, which was higher than the ratio of the other groups (p < 0.05).Conclusion: Pep-1 was conjugated and modified to PDA-TMZ NPs, which can serve as a new targeted drug nano-delivery system and can offer a CT and PTT integration therapy against GBM. Thus, Pep-1@PDA-TMZ NPs could be a feasible approach for efficient GBM therapy, and further provide some evidence and data for clinical transformation so that gradually conquer GBM.

Background: Mucopolysaccharidosis Type II (MPS II) is a rare, progressive and ultimately fatal X-linked lysosomal storage disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene. This report conducted a retrospective analysis to investigate the clinical characteristics, genotypes and management strategies in a large cohort of Chinese patients with MPS II.Methods: In this study, we explored 130 Chinese patients with MPS II between September 2008 and April 2022. Clinical manifestations, auxiliary examination, IDS pathogenic gene variants and IDS enzyme activity, surgical history were analysed in the study.Results: A total of 130 patients were enrolled and the mean age at diagnosis was 5 years old. This study found the most common symptoms in our patients were claw-like hands, followed by coarse facial features, birthmarks (Mongolian spot), delayed development, inguinal or umbilical hernia. The most commonly cardiac manifestations were valve abnormalities, which were mitral/tricuspid valve regurgitation (71.9%) and aortic/pulmonary valve regurgitation (36.8%). We had found 43 different IDS pathogenic gene variants in 55 patients, included 16 novel variants. The variants were concentrated in exon 9 (20% = 11/55), exon 3 (20% = 11/55) and exon 8 (15% = 8/55). A total of 50 patients (38.5%) underwent surgical treatment, receiving a total of 63 surgeries. The average age of first surgery was 2.6 years, and the majority of surgery (85.7%, 54/63) was operated before 4 years old. The most common and earliest surgery was hernia repair. Three patients were died of respiratory failure.Conclusion: This study provided additional information on the clinical, cardiac ultrasound and surgical procedure in MPS II patients. Our study expanded the genotype spectrum of MPS II. Based on these data, characterization of MPS II patients group could be used to early diagnosis and treatment of the disease.

BackgroundPsychiatric traits have been associated with intracerebral hemorrhage (ICH) in observational studies, although their causal relationships remain uncertain. We used Mendelian randomization analyses to infer causality between psychiatric traits and ICH.MethodsWe collected data from genome-wide association studies of ICH (n = 361,194) and eight psychiatric traits among Europeans, including mood swings (n = 451,619), major depressive disorder (n = 480,359), attention-deficit/hyperactivity disorder (n = 53,293), anxiety (n = 459,560), insomnia (n = 462,341), schizophrenia (n = 77,096), neuroticism (n = 374,323), and bipolar disorder (n = 51,710). We performed a series of bidirectional two-sample Mendelian randomization and related sensitivity analyses. A Bonferroni corrected threshold of p < 0.00625 (0.05/8) was considered to be significant, and p < 0.05 was considered suggestive of evidence for a potential association.ResultsMendelian randomization analyses revealed suggestive positive causality of mood swings on ICH (odds ratio = 1.006, 95% confidence interval = 1.001–1.012, p = 0.046), and the result was consistent after sensitivity analysis. However, major depressive disorder (p = 0.415), attention-deficit/hyperactivity disorder (p = 0.456), anxiety (p = 0.664), insomnia (p = 0.699), schizophrenia (p = 0.799), neuroticism (p = 0.140), and bipolar disorder (p = 0.443) are not significantly associated with the incidence of ICH. In the reverse Mendelian randomization analyses, no causal effects of ICH on mood swings (p = 0.565), major depressive disorder (p = 0.630), attention-deficit/hyperactivity disorder (p = 0.346), anxiety (p = 0.266), insomnia (p = 0.102), schizophrenia (p = 0.463), neuroticism (p = 0.261), or bipolar disorder (p = 0.985) were found.ConclusionOur study revealed that mood swings are suggestively causal of ICH and increase the risk of ICH. These results suggest the clinical significance of controlling mood swings for ICH prevention.

Summary: The function of the cancer-associated lncRNA Malat1 during aging is as-of-yet uncharacterized. Here, we show that Malat1 interacts with Nucleophosmin (NPM) in young mouse brain, and with Lamin A/C, hnRNP C, and KAP1 with age. RNA-seq and RT-qPCR reveal a persistent expression of Malat1_2 (the 3’isoform of Malat1) in Malat1Δ1 (5’-1.5 kb deletion) mouse retinas and brains at 1/4th level of the full-length Malat1, while Malat1_1 (the 5’isoform) in Malat1Δ2 (deletion of 3’-conserved 5.7 kb) at a much lower level, suggesting an internal promoter driving the 3’ isoform. The 1774 and 496 differentially expressed genes in Malat1Δ2 and Malat1Δ1 brains, respectively, suggest the 3’ isoform regulates gene expression in trans and the 5’ isoform in cis. Consistently, Malat1Δ2 mice show increased age-dependent retinal oxidative stress and corneal opacity, while Malat1Δ1 mice show no obvious phenotype. Collectively, this study reveals a physiological function of the lncRNA Malat1 3’-isoform during the aging process.

Direct visualization of metabolic dynamics in living animals with high spatial and temporal resolution is essential to understanding many biological processes. Here we introduce a platform that combines deuterium oxide (D2O) probing with stimulated Raman scattering (DO-SRS) microscopy to image in situ metabolic activities. Enzymatic incorporation of D2O-derived deuterium into macromolecules generates carbon-deuterium (C-D) bonds, which track biosynthesis in tissues and can be imaged by SRS in situ. Within the broad vibrational spectra of C-D bonds, we discover lipid-, protein-, and DNA-specific Raman shifts and develop spectral unmixing methods to obtain C-D signals with macromolecular selectivity. DO-SRS microscopy enables us to probe de novo lipogenesis in animals, image protein biosynthesis without tissue bias, and simultaneously visualize lipid and protein metabolism and reveal their different dynamics. DO-SRS microscopy, being noninvasive, universally applicable, and cost-effective, can be adapted to a broad range of biological systems to study development, tissue homeostasis, aging, and tumor heterogeneity.

A two-color vibrational imaging technique for simultaneously mapping glucose uptake and incorporation activity inside single living cells is reported. Heterogeneous patterns of glucose metabolism are directly visualized from the ratiometric two-color images for various cell types, cells undergoing epithelia-to-mesenchymal transitions and live mouse brain tissues. The two-color imaging of glucose metabolism here demonstrates the development of multi-functional vibrational probes for multicolor imaging of cellular metabolism.

Abstract Background Transient antenatal Bartter’s syndrome caused by MAGED2 mutation is a rare X-linked recessive renal tubular disorder. Cases reported are mostly infants, and the long-term prognosis of the disease is still under investigation. Case presentation We encountered a preterm male infant with polyhydramnios, polyuria, salt loss, hypercalciuria, nephrocalcinosis and alkalosis. Antenatal Bartter’s syndrome was suspected, but these clinical symptoms surprisingly disappeared after about 2 months. This led to the clinical diagnosis of transient antenatal Bartter’s syndrome. Gene analysis in this patient disclosed a novel variant (c.1598C > T, p.Ala533Val) in exon 12 of MAGED2 gene, and his mother was a heterozygous carrier. This patient was followed up in clinic for 4 years without recurrence of imbalance of potassium, sodium and chloride. His height and weight were in normal range, and all laboratory examinations and nephrotic ultrasound were also normal. Conclusions We reported the first Chinese case of transient antenatal Bartter’s syndrome caused by MAGED2 mutation. The 4-year follow-up of our case further demonstrates the benign prognosis of the disease and indicates that early recognition of this phenotype could avoid unnecessary treatments.

ObjectiveSelective dorsal rhizotomy (SDR) can decrease spasticity in children suffering from spastic cerebral palsy (SCP) and thus improve their moving ability when supplemented with the post-operational rehabilitation program. In this case, the study aims to investigate the gait changes in children with mild SCP after SDR in short-term follow-up.MethodsThe information of ambulatory SCP cases who underwent SDR in our center was retrospectively reviewed, and comparisons of changes in spasticity, motor function and data of gait analysis before and after SDR were analyzed.ResultsIn total, 32 cases were included in this study, with a mean age of 5.9 ± 2.1 years old. Noticeable decrease was found in the median value of the pre-operational MAS score after SDR at last follow-up in both sides of adductors, gastrocnemius, soleus, and left hamstrings. The Gross Motor Function Measure-66 score increased from 70.6 ± 9.2 to 73.4 ± 8.2, and the gait deviation index increased after SDR compared with the pre-operational data (right side: 65.8 ± 8.8 vs. 60.1 ± 10.7; left side: 63.5 ± 10.1 vs. 57.0 ± 9.9). Noticeable changes were found that the maximum angle of affected ankles in the sagittal plane (the dorsal-flexion angle) increased from 2.5° to 8.2°, the angles at initial contact (1% gait cycle) of affected knees in the sagittal plane decreased from 34.0° to 27.8°, and the angles at the end of swing phase (100% gait cycle) of affected knees in the sagittal plane decreased from 35.8° to 28.3°.ConclusionIn short-term follow-up, SDR can lower spasticity in children with SCP. Post-operational gait analysis showed improvements in gross motor function and gait, which derived from the changes in the sagittal plane (ankle and knee). A longer follow-up duration is thus needed to clarify the long-term outcome.

PM2.5 exposure can be associated with the onset of neurodegenerative diseases, with oxidative stress-induced cellular homeostasis disruption and cell death as one of the main mechanisms. However, the exact cellular and molecular processes are still rarely investigated. Autophagy and KEAP1-NRF2 (Kelch-like ECH-Associating protein 1-nuclear factor erythroid 2 related factor 2) signaling pathway are two main cellular defense systems for maintaining cellular homeostasis and resisting oxidative stress. In this study, we primarily investigated the role of autophagy and KEAP1-NRF2 in regulating cell death resulting from PM2.5 exposure in mouse neuroblastoma N2a cells. Our results showed that PM2.5 exposure disrupted autophagic flux by impairing lysosomal function, including lysosomal alkalinization, increased lysosome membrane permeabilization (LMP), and Cathepsin B release. Furthermore, dysregulated autophagy enhances NRF2 activity in a p62-dependent manner, which then initiates the expression of a series of antioxidant genes and increases cellular insensitivity to ferroptosis. Meanwhile, autophagy dysfunction impairs the intracellular degradation of ferroptosis related proteins such as GPX4 and ferritin. As these proteins accumulate, cells also become less sensitive to ferroptosis. LMP-associated cell death may be the main mechanism of PM2.5-induced N2a cytotoxicity. Our results may provide insights into the mechanisms of PM2.5-induced neurotoxicity and predict effective prevention and treatment strategies.

The functional interleukin 6 (IL-6) signaling complex is a hexameric structure composed of IL-6, IL-6Rα, and the signaling receptor gp130. There are three different modes of IL-6 signaling, classic signaling, trans-signaling, and trans-presentation, which are not functionally redundant and mediate pleiotropic effects on both physiological and pathophysiological states. Monoclonal antibodies against IL-6 or IL-6Rα have been successfully developed for clinical application. However, designing therapeutic interventions that block specific modes of IL-6 signaling in a pathologically relevant manner remains a great challenge. Here, we constructed a fusion protein Hyper-IL-6 (HyIL-6) composed of human IL-6 and IL-6Rα to develop specific blocking antibodies against the IL-6/IL-6Rα complex. We successfully screened the monoclonal antibody C14mab, which can bind to HyIL-6 with the binding constant 2.86 × 10−10 and significantly inhibit IL-6/IL-6Rα/gp130 complex formation. In vitro, C14mab effectively inhibited HyIL-6-stimulated signal transducer and activator of transcription 3 (STAT3) activation and related vascular endothelial growth factor (VEGF) induction. Moreover, C14mab efficaciously suppressed HyIL-6-induced acute phase response in vivo. Our data from hydrogen-deuterium exchange mass spectrometry demonstrate that C14mab mainly binds to site IIIa of IL-6 and blocks the final step in the interaction between gp130 and IL-6/IL-6Rα complex. Additionally, data from enzyme-linked immunosorbent assays and kinetics assays indicate that C14mab interacts simultaneously with IL-6 and IL-6Rα, while it does not interact with IL-6Rα alone. The unique features of C14mab may offer a novel alternative for IL-6 blockade and illuminate a better therapeutic intervention targeting IL-6.

Resistance remains an obstacle to anti-programmed cell death protein 1 (PD-1) therapy in human cancer. One critical resistance mechanism is the lack of T cell chemotaxis in the tumor microenvironment (TME). CXCL10-CXCR3 signaling is required for T cell tumor infiltration and tumor immunotherapy. Oncolytic viruses (OVs), including oncolytic adenoviruses (AdVs), induce effective T cell immunity and tumor infiltration. Thus, arming OV with CXCL10 would be an attractive strategy to overcome resistance to anti-PD1 therapy. Here, we successfully constructed a novel recombinant oncolytic adenovirus encoding murine CXCL10, named Adv-CXCL10. Through intratumoural injection, the continuous expression of the functional chemokine CXCL10 in the TME is realized to recruit more CXCR3+ T cells into the TME to kill tumor cells, and the recombinant adenovirus shows great power to ‘fire up’ the TME and enhance the antitumour efficiency of PD-1 antibodies.

Membrane phase behavior has been well characterized in model membranes in vitro under thermodynamic equilibrium state. However, the widely observed differences between biological membranes and their in vitro counterparts are placing more emphasis on nonequilibrium factors, including influx and efflux of lipid molecules. The endoplasmic reticulum (ER) is the largest cellular membrane system and also the most metabolically active organelle responsible for lipid synthesis. However, how the nonequilibrium metabolic activity modulates ER membrane phase has not been investigated. Here, we studied the phase behavior of functional ER in the context of lipid metabolism. Utilizing advanced vibrational imaging technique, that is, stimulated Raman scattering microscopy, we discovered that metabolism of palmitate, a prevalent saturated fatty acid (SFA), could drive solid-like domain separation from the presumably uniformly fluidic ER membrane, a previously unknown phenomenon. The potential of various fatty acids to induce solid phase can be predicted by the transition temperatures of their major metabolites. Interplay between saturated and unsaturated fatty acids is also observed. Hence, our study sheds light on cellular membrane biophysics by underscoring the nonequilibrium metabolic status of living cell.