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Abstract Objectives Patients with traumatic brain injury (TBI) often suffer memory and cognitive impairments, and oxiracetam‐like drugs are considered to have a positive impact on these symptoms potentially. However, the efficacy and safety of L‐oxiracetam and oxiracetam in TBI patients have not been sufficiently investigated. Methods The study adopts a multicenter, randomized, double‐blind, parallel‐group, phase 3 clinical trial design in 74 centers across 51 hospitals in China. A total of 590 TBI patients meeting criteria will be randomly allocated into three groups in a 2:2:1 ratio: L‐oxiracetam group, oxiracetam group, and placebo group. The treatment period is 14 days, with a follow‐up period of 90 days. The primary outcome measure is the change in the Loewenstein Occupational Therapy Cognitive Assessment score at 90 days after treatment. Secondary outcomes include changes in other cognitive assessments, neurological function, activities of daily living, and safety assessments. Discussion There is no robust evidence to suggest that L‐oxiracetam and oxiracetam can enhance memory and cognitive function in patients with mild to moderate TBI. This study has the potential to answer this crucial clinical question. Trial registration chinadrugtrials.org.cn, identifier CTR20192539; ClinicalTrials.gov, identifier NCT04205565.

Background: Traumatic brain injury (TBI) is a common neurosurgical disease in emergency rooms with poor prognosis, imposing severe burdens on patients and their families. Evidence indicates that piracetam and compound porcine cerebroside and ganglioside injection (CPCGI) can improve cognitive levels in TBI patients to enhance functional prognosis, but there is still a research gap regarding the efficacy of CPCGI. This study aims to determine the effectiveness and safety of CPCGI in improving cognitive and functional outcomes in TBI patients. Methods: This study is a multicenter, randomized, parallel-group, double-blind trial aiming to recruit 900 adult patients with mild to moderate TBI. After providing informed consent, 600 patients will be randomly assigned to the CPCGI group (20 ml/d, for 14 days), and 300 patients will be randomized to the piracetam group as a control (20 ml/d, for 14 days), followed up for 3 months after treatment. The primary outcome is the change in the Montreal Cognitive Assessment (MoCA) score from baseline after 3 months. The main secondary outcome measures include Mini-Mental State Examination (MMSE) scores, Glasgow Outcome Scale-Extended (GOS-E), and the Barthel Index at 1 and 3 months. Discussion: This multi-center clinical trial aims to provide high-quality evidence on the efficacy and safety of CPCGI in improving cognitive and functional outcomes in mild to moderate TBI patients. Trial registration: ChiCTR2000040466, date of registration: November 28, 2020.

Abstract This study aimed to investigate the predictive factors of therapeutic efficacy for chronic subdural hematoma (CSDH) patients receiving atorvastatin combined with dexamethasone therapy by using clinical imaging characteristics in conjunction with computed tomography (CT) texture analysis (CTTA). Clinical imaging characteristics and CT texture parameters at admission were retrospectively investigated in 141 CSDH patients who received atorvastatin combined with dexamethasone therapy from June 2019 to December 2022. The patients were divided into a training set (n = 81) and a validation set (n = 60). Patients in the training data were divided into two groups based on the effectiveness of the treatment. Univariate and multivariate analyses were performed to assess the potential factors that could indicate the prognosis of CSDH patients in the training set. The receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of the significant factors in predicting the prognosis of CSDH patients and was validated using a validation set. The multivariate analysis showed that the hematoma density to brain parenchyma density ratio, singal min (minimum) and singal standard deviation of the pixel distribution histogram, and inhomogeneity were independent predictors for the prognosis of CSDH patients based on atorvastatin and dexamethasone therapy. The area under the ROC curve between the two groups was between 0.716 and 0.806. As determined by significant factors, the validation's accuracy range was 0.816 to 0.952. Clinical imaging characteristics in conjunction with CTTA could aid in distinguishing patients with CSDH who responded well to atorvastatin combined with dexamethasone.

Abstract Gastric cancer (GC) represents a significant burden of cancer-related mortality worldwide, underscoring an urgent need for the development of early detection strategies and precise postoperative interventions. However, the identification of non-invasive biomarkers for early diagnosis and patient risk stratification remains underexplored. Here, we conduct a targeted metabolomics analysis of 702 plasma samples from multi-center participants to elucidate the GC metabolic reprogramming. Our machine learning analysis reveals a 10-metabolite GC diagnostic model, which is validated in an external test set with a sensitivity of 0.905, outperforming conventional methods leveraging cancer protein markers (sensitivity

Abstract Background Despite its prevalence, there is ongoing debate regarding the optimal management strategy for chronic subdural hematoma (CSDH), reflecting the variability in clinical presentation and treatment outcomes. This ambidirectional, nationwide, multicenter registry study aims to assess the efficacy and safety of multimodality treatment approaches for CSDH in the Chinese population. Methods/design A multicenter cohort of CSDH patients from 59 participating hospitals in mainland China was enrolled in this study. The treatment modalities encompassed a range of options and baseline demographics, clinical characteristics, radiographic findings, and surgical techniques were documented. Clinical outcomes, including hematoma resolution, recurrence rates, neurological status, and complications, were assessed at regular intervals during treatment, 3 months, 6 months, 1 year, and 2 years follow-up. Result Between March 2022 and August 2023, a comprehensive cohort comprising 2173 individuals who met the criterion was assembled across 59 participating clinical sites. Of those patients, 81.1% were male, exhibiting an average age of 70.12 ± 14.53 years. A historical record of trauma was documented in 48.0% of cases, while headache constituted the predominant clinical presentation in 58.1% of patients. The foremost surgical modality employed was the burr hole (61.3%), with conservative management accounting for 25.6% of cases. Notably, a favorable clinical prognosis was observed in 88.9% of CSDH patients at 3 months, and the recurrence rate was found to be 2.4%. Conclusion This registry study provides critical insights into the multimodality treatment of CSDH in China, offering a foundation for advancing clinical practices, optimizing patient management, and ultimately, improving the quality of life for individuals suffering from this challenging neurosurgical condition. Trial registration ChiCTR2200057179

Traumatic Brain Injury (TBI) is a prevalent form of neurological damage that may induce varying degrees of cognitive dysfunction in patients, consequently impacting their quality of life and social functioning. This article provides a mini review of the epidemiology in Chinese TBI patients and etiology of cognitive impairment. It analyzes the risk factors of cognitive impairment, discusses current management strategies for cognitive dysfunction in Chinese TBI patients, and summarizes the strengths and limitations of primary testing tools for TBI-related cognitive functions. Furthermore, the article offers a prospective analysis of future challenges and opportunities. Its objective is to contribute as a reference for the prevention and management of cognitive dysfunction in Chinese TBI patients.

Summary: Background: The pathology of keloid and especially the roles of bacteria on it were not well understood. Methods: In this study, multi-omics analyses including microbiome, metaproteomics, metabolomic, single-cell transcriptome and cell-derived xenograft (CDX) mice model were used to explore the roles of bacteria on keloid disease. Findings: We found that the types of bacteria are significantly different between keloid and healthy skin. The 16S rRNA sequencing and metaproteomics showed that more catalase (CAT) negative bacteria, Clostridium and Roseburia existed in keloid compared with the adjacent healthy skin. In addition, protein mass spectrometry shows that CAT is one of the differentially expressed proteins (DEPs). Overexpression of CAT inhibited the proliferation, migration and invasion of keloid fibroblasts, and these characteristics were opposite when CAT was knocked down. Furthermore, the CDX model showed that Clostridium butyricum promote the growth of patient's keloid fibroblasts in BALB/c female nude mice, while CAT positive bacteria Bacillus subtilis inhibited it. Single-cell RNA sequencing verified that oxidative stress was up-regulated and CAT was down-regulated in mesenchymal-like fibroblasts of keloid. Interpretation: In conclusion, our findings suggest that bacteria and CAT contribute to keloid disease. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Abstract The LuxS quorum sensing system is a widespread system employed by many bacteria for cell-to-cell communication. The luxS gene has been demonstrated to play a crucial role in intramacrophage survival of piscine Streptococcus agalactiae, but the underlying mechanism remains largely unknown. In this study, transcriptome analysis, followed by the luxS gene deletion and subsequent functional studies, confirmed that impaired bacterial survival inside macrophages due to the inactivation of luxS was associated with reduced transcription of the fruRKI operon, encoding the fructose-specific phosphotransferase system. Further, luxS was determined not to enhance the transcription of fruRKI operon by binding its promoter, but to upregulate the expression of this operon via affecting the binding ability of catabolite control protein A (CcpA) to the catabolite responsive element (cre) in the promoter of fruRKI. Collectively, our study identifies a novel and previously unappreciated role for luxS in bacterial intracellular survival, which may give a more thorough understanding of the immune evasion mechanism in S. agalactiae.

Abstract The persistent dysregulation and accumulation of poisonous proteins from destructive neural tissues and cells activate pathological mechanisms after traumatic brain injury (TBI). The lymphatic drainage system of the brain, composed of the glymphatic system and meningeal lymphatic vessels (MLVs), plays an essential role in the clearance of toxic waste after brain injury. The neuroprotective effect of interleukin 33 (IL-33) in TBI mice has been demonstrated; however, its impact on brain lymphatic drainage is unclear. Here, we established a fluid percussion injury model to examine the IL-33 administration effects on neurological function and lymphatic drainage in the acute brain of TBI mice. We verified that exogenous IL-33 could improve the motor and memory skills of TBI mice and demonstrated that in the acute phase, it increased the exchange of cerebrospinal and interstitial fluid, reversed the dysregulation and depolarization of aquaporin-4 in the cortex and hippocampus, improved the drainage of MLVs to deep cervical lymph nodes, and reduced tau accumulation and glial activation. We speculate that the protective effect of exogenous IL-33 on TBI mice’s motor and cognitive functions is related to the enhancement of brain lymphatic drainage and toxic metabolite clearance from the cortex and hippocampus in the acute stage. These data further support the notion that IL-33 therapy may be an effective treatment strategy for alleviating acute brain injury after TBI.

Due to the difficulties in designing sensor arrays with a wide detection range, high sensitivity, and the sensing ability to convert tangential force into normal force on the same substrate, the integration of shape and texture recognitions in one electronic skin (e‐skin) has not been realized so far. Herein, an e‐skin tactile‐sensing system is presented, based on resistive pressure‐sensing units (serving as Meissner corpuscles) unevenly distributed on a bionic hand‐shaped polyimide substrate, which can realize shape and texture recognitions concurrently. A multilayer microporous structure with different pores is designed and introduced into the sensor, which enables each sensing unit ultrahigh sensitivity and a wide detection range. Meanwhile, a customized micro‐pyramid array is developed and assembled to the sensor array, which realizes the transformation from tangential force to normal force. With the help of artificial intelligence technology, the recognition accuracy reaches 100% for 8 different shapes, and 99.7% for 10 different textures, respectively. The proposed design strategy enables compatible fabrication, simple signal processing, and convenient extension of bionic free‐shaped e‐skin, which paves a promising way for the popularization of e‐skin in large‐scale intelligent wearable fields.

Wearable recognition systems based on flexible electronics present immense potential for applications in human–machine interfaces, medical care, soft robots, etc. However, they experience challenges in terms of the nonideal consistency and stability of flexible sensors, which are responsible for detecting physical signals from human motions. These challenges hinder the improvement of recognition precision and capability in the wearable systems. Furthermore, the computational consumption for the recognition increases as more sensors are used to extensively gather information for distinguishing between complex motions. Herein, a wearable recognition system based on deep‐learning‐enhanced strain sensors for distinguishing between the complex motions of the human body is presented. A strain sensor based on peak–valley microstructures is fabricated and packaged to improve consistency and stability. Moreover, a lightweight hybrid convolutional neural network long short‐term memory model is designed to lower the computational costs of the deep learning process. In particular, by designing Butterworth filtering and Z‐score normalization algorithms, the error in feature extraction caused by sensor signal fluctuation is reduced, thereby improving the recognition accuracy of the proposed wearable system to 95.72% for seven gait motions and 100% for four different continuous series of Tai Chi forms.

Abstract Due to the complicated relationship between wearable electronics performance and various parameters, months even years are needed to obtain a desired sensor by random and time‐consuming trial‐and‐error methods. Herein, a general analytic model based on the micro‐element division and equivalent circuit is presented to guide a rapid optimizing strategy for wearable resistive pressure sensors, which is like the method always used in the traditional design of the metal‐oxide‐semiconductor field‐effect transistor for integrated circuits. The quantitative relationship between the sensitivity and related parameters is declared in the presented model, and the optimized parameters are achieved to design a sensor. The demanded ultra‐highly sensitive pressure sensor is successfully designed and optimized in minutes based on the built model, and the fabricated sensor is applied in a voice real‐time recognition system to obtain 100% recognition accuracy. The on‐demand and agile development strategy paves a promising way to greatly accelerate the transition from random and time‐consuming to the controllable design of wearable electronics.

Abstract Background The discovery of the glymphatic system and meningeal lymphatic vessels challenged the traditional view regarding the lack of a lymphatic system in the central nervous system. It is now known that the intracranial lymphatic system plays an important role in fluid transport, macromolecule uptake, and immune cell trafficking. Studies have also shown that the function of the intracranial lymphatic system is significantly associated with neurological diseases; for example, an impaired intracranial lymphatic system can lead to Tau deposition and an increased lymphocyte count in the brain tissue of mice with subarachnoid hemorrhage. Methods In this study, we assessed the changes in the intracranial lymphatic system after intracerebral hemorrhage and the regulatory effects of repeated transcranial magnetic stimulation on the glymphatic system and meningeal lymphatic vessels in an intracerebral hemorrhage (ICH) model of male mice. Experimental mice were divided into three groups: Sham, ICH, and ICH + repeated transcranial magnetic stimulation (rTMS). Three days after ICH, mice in the ICH+rTMS group were subjected to rTMS daily for 7 days. Thereafter, the function of the intracranial lymphatic system, clearance of RITC‐dextran and FITC‐dextran, and neurological functions were evaluated. Results Compared with the Sham group, the ICH group had an impaired glymphatic system. Importantly, rTMS treatment could improve intracranial lymphatic system function as well as behavioral functions and enhance the clearance of parenchymal RITC‐dextran and FITC‐dextran after ICH. Conclusion Our results indicate that rTMS can abrogate ICH‐induced brain parenchymal metabolite clearance dysfunction by regulating intracranial lymphatic drainage.

Protozoan predation has been demonstrated to be a strong driving force for bacterial defence strategies in the environment. Our previous study demonstrated that Aeromonas hydrophila NJ-35, which evolved small-colony variants (SCVs), displayed various adaptive traits in response to Tetrahymena thermophila predation, such as enhanced phage resistance. However, the evolutionary mechanisms are largely unknown. In this study, we performed a genome- and transcriptome-wide analysis of the SCV1, representing one strain of the SCVs, for identification of the genes of mutation and altered expression underlying this phage resistance phenotype. Our study demonstrated that phage resistance caused by T. thermophila predation was due to the downregulation of a flagellar biosynthesis regulator, flhF, in SCV1. Interestingly, we confirmed that phage resistance in SCV1 was not straightforwardly attributable to the absence of flagella but to FlhF-mediated secretion of extracellular protein that hinders phage adsorption. This finding improves our understanding of the mechanisms by which A. hydrophila lowers the susceptibility to phage infection under predation pressure, and highlights an important contribution of bacterium–protozoan interactions in driving the adaptive evolution of pathogens in complex environments.

Compared with single and randomly distributed defects, arrayed defects exist widely in the film structure and can be designed artificially to achieve various specific functions. However, the mechanical behavior of transition metal dihalides with dislocation array defects is unclear; this limits their application in new flexible nanodevices. In this study, the strength and fracture properties of monolayer MoS2 films containing 5|7 (S5|7 and Mo5|7) dislocation defects under uniaxial tension were studied by molecular dynamics simulation. The results show that the number of defects, adjacent spacing, and alignment angle affect the critical strain and tensile strength of the monolayer MoS2 films. These results provide a basis for further understanding the mechanical behavior of monolayer MoS2 thin films and provide a theoretical reference for the application of nano-electronic devices based on MoS2.

BackgroundPulmonary infection caused by multidrug-resistant Acinetobacter baumannii (MDR-AB) is a common and serious complication after brain injury. There are no definitive methods for its prediction and it is usually accompanied by a poor prognosis. This study aimed to construct and evaluate a nomogram based on patient data from the neurosurgical intensive care unit (NSICU) to predict the probability of MDR-AB pulmonary infection.MethodsIn this study, we retrospectively collected patient clinical profiles, early laboratory test results, and doctors’ prescriptions (66 variables). Univariate and backward stepwise regression analyses were used to screen the variables to identify predictors, and a nomogram was built in the primary cohort based on the results of a logistic regression model. Discriminatory validity, calibration validity, and clinical utility were evaluated using validation cohort 1 based on receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA). For external validation based on predictors, we prospectively collected information from patients as validation cohort 2.ResultsAmong 2115 patients admitted to the NSICU between December 1, 2019, and December 31, 2021, 217 were eligible for the study, including 102 patients with MDR-AB infections (102 cases) and 115 patients with other bacterial infections (115 cases). We randomly categorized the patients into the primary cohort (70%, N=152) and validation cohort 1 (30%, N=65). Validation cohort 2 consisted of 24 patients admitted to the NSICU between January 1, 2022, and March 31, 2022, whose clinical information was prospectively collected according to predictors. The nomogram, consisting of only six predictors (age, NSICU stay, Glasgow Coma Scale, meropenem, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio), had significantly high sensitivity and specificity (primary cohort AUC=0.913, validation cohort 1 AUC=0.830, validation cohort 2 AUC=0.889) for early identification of infection and had great calibration (validation cohort 1,2 P=0.3801, 0.6274). DCA confirmed that the nomogram is clinically useful.ConclusionOur nomogram could help clinicians make early predictions regarding the onset of pulmonary infection caused by MDR-AB and implement targeted interventions.

Abstract Accurate motion feature extraction and recognition provide critical information for many scientific problems. Herein, a new paradigm for a wearable seamless multimode sensor with the ability to decouple pressure and strain stimuli and recognize the different joint motion states is reported. This wearable sensor is integrated into a unique seamless structure consisting of two main parts (a resistive component and a capacitive component) to decouple the different stimuli by an independent resistance-capacitance sensing mechanism. The sensor exhibits both high strain sensitivity (GF = 7.62, 0–140% strain) under the resistance mechanism and high linear pressure sensitivity (S = 3.4 kPa−1, 0–14 kPa) under the capacitive mechanism. The sensor can differentiate the motion characteristics of the positions and states of different joints with precise recognition (97.13%) with the assistance of machine learning algorithms. The unique integrated seamless structure is achieved by developing a layer-by-layer casting process that is suitable for large-scale manufacturing. The proposed wearable seamless multimode sensor and the convenient process are expected to contribute significantly to developing essential components in various emerging research fields, including soft robotics, electronic skin, health care, and innovative sports systems applications.

Abstract Metabolic reprogramming evolves during cancer initiation and progression. However, thorough understanding of metabolic evolution from preneoplasia to lung adenocarcinoma (LUAD) is still limited. Here, we perform large-scale targeted metabolomics on resected lesions and plasma obtained from invasive LUAD and its precursors, and decipher the metabolic trajectories from atypical adenomatous hyperplasia (AAH) to adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC), revealing that perturbed metabolic pathways emerge early in premalignant lesions. Furthermore, three panels of plasma metabolites are identified as non-invasive predictive biomarkers to distinguish IAC and its precursors with benign diseases. Strikingly, metabolomics clustering defines three metabolic subtypes of IAC patients with distinct clinical characteristics. We identify correlation between aberrant bile acid metabolism in subtype III with poor clinical features and demonstrate dysregulated bile acid metabolism promotes migration of LUAD, which could be exploited as potential targetable vulnerability and for stratifying patients. Collectively, the comprehensive landscape of the metabolic evolution along the development of LUAD will improve early detection and provide impactful therapeutic strategies.

Although first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy is effective for treating EGFR-mutant non–small cell lung cancer (NSCLC), it is now understood that drug-tolerant persister (DTP) cells escaping from initial treatment eventually drives drug resistance. Here, through integration of metabolomics and transcriptomics, we found that the neurotransmitter acetylcholine (ACh) was specifically accumulated in DTP cells, and demonstrated that treatment with EGFR-TKI heightened the expression of the rate-limiting enzyme choline acetyltransferase (ChAT) in ACh biosynthesis via YAP mediation. Genetic and pharmacological manipulation of ACh biosynthesis or ACh signaling could predictably regulate the extent of DTP formation in vitro and in vivo. Strikingly, pharmacologically targeting ACh/M3R signaling with an FDA-approved drug, darifenacin, retarded tumor relapse in vivo. Mechanistically, upregulated ACh metabolism mediated drug tolerance in part through activating WNT signaling via ACh muscarinic receptor 3 (M3R). Importantly, we showed that aberrant ACh metabolism in patients with NSCLC played a potential role in predicting EGFR-TKI response rate and progression-free survival. Our study therefore defines a therapeutic strategy — targeting the ACh/M3R/WNT axis — for manipulating EGFR TKI drug tolerance in the treatment of NSCLC.

Abstract Background We have recently showed that atorvastatin (ATO) combined with low dose of dexamethasone (DEX) was more efficacious in treating patients with chronic subdural haematoma (CSDH) than ATO monotherapy. This study was designed to investigate the underlying mechanisms of the improved efficacy of this combined therapy. Methods Mass spectrometry was performed to quantitatively detect drugs in haematoma fluids and serum samples from CSDH patients and also in cultured macrophages after treatment with either ATO alone or in combination with DEX. The differentiation and apoptosis of macrophages were evaluated using flow cytometry. The expression of cytokines, chemokines and angiogenesis-related proteins was evaluated using proteome profile arrays, immunoblots and ELISA, respectively. Results ATO was detected in haematoma fluids and serum samples, whose levels were increased significantly in samples collected from patients treated with both ATO and DEX. ATO was also increased in cultured macrophages treated with ATO and DEX. The numbers of M1-polarized macrophages were higher than the M2 phenotype in the haematoma fluids of patients. Cultured macrophages treated with ATO and DEX had reduced numbers of M1-polarized macrophages, increased numbers of M2-polarized macrophages as compared to monotherapies, and decreased rate of apoptosis induced by high-dose DEX. DEX enhanced the anti-inflammatory and anti-angiogenic activity of ATO by suppressing VEGFA and other inflammatory angiogenic factors. Consistent with the finding, patients responded well to the drug treatments had lower serum levels of VEGFA. Conclusions We have shown for the first time that ATO given orally was detected in CSDH haematoma fluids. DEX enhances the anti-inflammatory and anti-angiogenic effects of ATO, primarily by increasing the presence of ATO in haematoma and macrophages and by regulating the functions of macrophages.

ABSTRACT The clustered regularly interspaced palindromic repeat (CRISPR)-associated (Cas) system functions classically as a prokaryotic defense system against invading mobile genetic elements, such as phages, plasmids, and viruses. Our previous study revealed that CRISPR deletion caused increased transcription of capsular polysaccharide (CPS) synthesis-related genes and severely attenuated virulence in the hypervirulent piscine Streptococcus agalactiae strain GD201008-001. Here, we found that CRISPR deficiency resulted in reduced adhesion, invasion, and biofilm formation abilities in this strain by upregulating the production of CPS. However, enhanced CPS production was not responsible for the attenuated phenotype of the ΔCRISPR mutant. RNA degradation assays indicated that inhibited transcription of the cps operon by CRISPR RNA (crRNA) was not due to the base pairing of the crRNA with the cps mRNA but to the repression of the promoter activity of cpsA, which is a putative transcriptional regulator of the capsule locus. IMPORTANCE Beyond protection from invading nucleic acids, CRISPR-Cas systems have been shown to have an important role in regulating bacterial endogenous genes. In this study, we demonstrate that crRNA inhibits the transcription of the cps operon by repressing the activity of promoter PcpsA, leading to increases in the abilities of adhesion, invasion, and biofilm formation in S. agalactiae. This study highlights the regulatory role of crRNA in bacterial physiology and provides a new explanation for the mechanism of crRNA-mediated endogenous gene regulation in S. agalactiae.

Subdural hematoma (SDH) is one of the most lethal types of traumatic brain injury. SDH caused by Intracranial Pressure Reduction (ICPR) is rare, and the mechanism remains unclear. Here, we report three cases of SDH that occurred after substandard cupping therapy and are conjected to be associated with ICPR. All of them had undergone cupping treatments. On the last cupping procedure, they experienced a severe headache after the cup placed on the occipital-neck junction (ONJ) was suddenly removed and were diagnosed with SDH the next day. In standard cupping therapy, the cups are not usually placed on the ONJ. We speculate that removing these cups on the soft tissue over the cisterna magna repeatedly created localized negative pressure, caused temporary but repeated ICPR, and eventually led to SDH development. The Monro-Kellie Doctrine can explain the mechanism behind this - it states that the intracranial pressure is regulated by a fixed system, with any change in one component causing a compensatory change in the other. The repeated ICPR promoted brain displacement, tearing of the bridging veins, and development of SDH. The literature was reviewed to illustrate the common etiologies and therapies of secondary ICPR-associated SDH. Despite the popularity of cupping therapy, its side effects are rarely mentioned. This case is reported to remind professional technicians to fully assess a patient's condition before cupping therapy and ensure that the cups are not placed at the ONJ.

Base stability for a wheeled robot while driving over rough terrain is a challenging issue. This paper proposes a novel base-stability control framework, consisting of an AVIC (adaptive variable-impedance control), AVIC-based tracking controller, and a THV (terrain height variation) and AC (attitude control) AC-based controller to stabilize the base on rough terrain. The AVIC-based controller aims to track the desired trajectory of the robot base while suppressing lumped disturbance, including system uncertainties in the internal dynamics and unknown external disturbance. The THV-based controller is utilized as a feedforward controller to improve posture tracking performance in order to achieve a horizontal posture. The AC-based controller is employed to maintain the horizontal posture of the base. The effectiveness and robustness of the proposed controllers are validated by a series of numerical trials, and the results are evaluated.

This work studies the use of Fe/Ni-MOFs for the removal of ciprofloxacin (CIP) in wastewater. Fe/Ni-MOFs are prepared by the solvothermal method and characterized by X-ray diffraction (XRD), a scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FT-IR), and a thermal gravimetric analyzer (TG). Under the conditions of the concentration of 50 ppm, a mass of 30 mg, and a temperature of 30 °C, the maximum adsorption capacity of ciprofloxacin removal within 5 h was 232.1 mg/g. The maximum removal rate was 94.8% when 40 mg of the Fe/Ni-MOFs was added to the solution of 10 ppm ciprofloxacin. According to the pseudo-second-order (PSO) kinetic model, the R2 values were all greater than 0.99, which proved that the adsorption theory of ciprofloxacin by Fe/Ni-MOFs was consistent with the practice. The adsorption results were mainly affected by solution pH and static electricity, as well as other factors. The Freundlich isotherm model characterized the adsorption of ciprofloxacin by Fe/Ni-MOFs as multilayer adsorption. The above results indicated that Fe/Ni-MOFs were effective in the practical application of ciprofloxacin removal.

Abstract p97/VCP, an evolutionarily concerned ATPase, partakes in multiple cellular proteostatic processes, including the endoplasmic reticulum (ER)-associated protein degradation (ERAD). Elevated expression of p97 is common in many cancers and is often associated with poor survival. Here we report that the levels of p97 positively correlated with the histological grade, tumor size, and lymph node metastasis in breast cancers. We further examined p97 expression in the stem-like cancer cells or cancer stem cells (CSCs), a cell population that purportedly underscores cancer initiation, therapeutic resistance, and recurrence. We found that p97 was consistently at a higher level in the CD44+/CD24−, ALDH+, or PKH26+ CSC populations than the respective non-CSC populations in human breast cancer tissues and cancer cell lines and p97 expression also positively correlated with that of SOX2, another CSC marker. To assess the role of p97 in breast cancers, cancer proliferation, mammosphere, and orthotopic growth were analyzed. Similarly as p97 depletion, two pharmacological inhibitors, which targets the ER-associated p97 or globally inhibits p97’s ATPase activity, markedly reduced cancer growth and the CSC population. Importantly, depletion or inhibition of p97 greatly suppressed the proliferation of the ALDH+ CSCs and the CSC-enriched mammospheres, while exhibiting much less or insignificant inhibitory effects on the non-CSC cancer cells. Comparable phenotypes produced by blocking ERAD suggest that ER proteostasis is essential for the CSC integrity. Loss of p97 gravely activated the unfolded protein response (UPR) and modulated the expression of multiple stemness and pluripotency regulators, including C/EBPδ, c-MYC, SOX2, and SKP2, which collectively contributed to the demise of CSCs. In summary, p97 controls the breast CSC integrity through multiple targets, many of which directly affect cancer stemness and are induced by UPR activation. Our findings highlight the importance of p97 and ER proteostasis in CSC biology and anticancer therapy.

Metabolism changes can modulate immune responses in many contexts, and vice versa. Here the authors associate metabolomic, as well as cytokine and chemokine, data from stratified COVID-19 patients to find that arginine, tryptophan and purine metabolic pathways correlate with hyperproliferation, thus hinting at potential therapeutic targets for severe COVID-19 patients.

The clustered regularly interspaced palindromic repeats (CRISPR)-Cas (CRISPR-associated) system is a prokaryotic defence against invading mobile genetic elements, such as bacteriophages or exogenous plasmids. Beyond this, this system has been shown to play an important role in controlling the virulence of some bacterial pathogens. Streptococcus agalactiae strain GD201008-001, a causative agent of septicemia and meningitis in tilapia, contains a single type II CRISPR-Cas system with Cas9 as a signature protein. In this study, we found that the deletion of CRISPR significantly reduced adhesion, invasion, cytotoxicity and haemolysis, and caused severely attenuated virulence in the piscine S. agalactiae strain. RNA-Seq identified 236 endogenous genes regulated by CRISPR, with 159 genes upregulated and 77 genes downregulated. The resulting change in gene transcription by CRISPR was much more pronounced than that by cas9 in this bacterium, indicating CRISPR-mediated endogenous gene regulation was mostly independently of cas9. Subsequent studies showed that CovR/S two-component system was transcriptionally upregulated due to CRISPR deletion, which repressed the expression of the cylE gene coding for a cytolytic toxin, and thus decreased the activity of β-haemolysin/cytolysin. However, upregulation of CovR/S was not the contributor to the attenuation phenotype of ΔCRISPR. Further, we demonstrated that CRISPR is capable of repressing the expression of Toll-like receptor 2 (TLR2)-activating lipoprotein Sag0671 and thus dampens the innate immune response. This study revealed that the CRISPR system of S. agalactiae exhibited extraordinary potential capability in the regulation of endogenous transcripts, which contributes to bacterial innate immune evasion and virulence.

Summary: Background: Chronic subdural hematoma (CSDH) is a common neurological disease, and the surgical evacuation of subdural collection remains the primary treatment approach for symptomatic patients. Postoperative recurrence is a serious complication, and several factors are correlated with postoperative recurrence. Methods: We searched Embase, Web of Science, PubMed, and Cochrane Library from their establishment to September 2020. Reports on randomized, prospective, retrospective, and overall observational studies on the management of surgical patients with CSDH were searched, and an independent reviewer performed research quality assessment. Factors that affect the postoperative recurrence of CSDH were extracted: social demographics, drugs (as the main or auxiliary treatment), surgical management, imaging, and other risk factors. We evaluated the recurrence rate of each risk factor. A random effect model was used to perform a meta-analysis, and each risk factor affecting the postoperative recurrence of CSDH was then evaluated and graded. Findings: In total, 402 studies were included in this analysis and 32 potential risk factors were evaluated. Among these, 21 were significantly associated with the postoperative recurrence of CSDH. Three risk factors (male, bilateral hematoma, and no drainage) had convincing evidence. The classification of evidence can help clinicians identify significant risk factors for the postoperative recurrence of CSDH. Interpretation: Only few associations were supported by high-quality evidence. Factors with high-quality evidence may be important for treating and preventing CSDH recurrence. Our results can be used as a basis for improving clinical treatment strategies and designing preventive methods. Funding: No funding was received.

We are not aware of any reports regarding conservative treatment for leukemia-related chronic subdural hematoma (CSDH). We report our experience with 3 men who were admitted with subdural masses and abnormal leukocyte counts. In two patients, leukemia and CSDH were confirmed on the basis of medical records, mild head trauma, and neuroimaging features. Both patients experienced reduced CSDH and neurological symptoms after receiving atorvastatin (20 mg/day) plus low-dose dexamethasone. However, this combined conservative treatment was ineffective in the third patient, who was diagnosed as having leukemia and showed an increased hematoma volume after two weeks of therapy. Magnetic resonance imaging findings suggested dural metastasis, which prompted a switch from statin-based conservative treatment to chemotherapy. Complete remission of the leukemia and resolution of the subdural mass were observed after chemotherapy, which supported a diagnosis of leukemia encephalopathy. The 5-month follow-ups did not reveal CSDH relapse in all 3 cases. Thus, atorvastatin-based conservative treatment may be effective for leukemia-related CSDH but not for leukemia encephalopathy.

This study was conducted to simulate the causes of, and suppress, the scratch damage on the workpiece surface during magnetorheological surface polishing. The molecular dynamics method combined with polishing contact trajectory modeling was used to simulate the scratch damage formation process, and the scratch damage morphology model was established by analyzing the scratch damage distribution characteristics in the magnetorheological plane polishing process. The effect of different process parameters on the scratch damage characteristics was predicted by simulation, and orthogonal experiments were designed to explore the preferred polishing process parameters that could suppress the scratch damage formation. Finally, it was further verified that the formation of scratch damage can be effectively suppressed by controlling the workpiece speed, polishing disc speed, and magnetic field generator speed, and adjusting the magnetic field eccentricity distance under the premise of ensuring the surface roughness and flatness of the workpiece.

Fe-MOFs were prepared using a solvothermal method, and were characterized by scanning electron microscopy. We explored the application of Fe-MOFs as an adsorbing material for the removal of Rhodamine B (RhB) from aqueous solutions. The experimental data were simulated by dynamics and the results showed that the pseudo–second-order kinetics model was appropriate for analysis of RhB removal. We studied the adsorption capacity of MOF materials under different masses, concentrations, and pH conditions. When the pH was 6, the maximum adsorption capacity within 4 h was 135 mg/g. In summation, the removal of RhB from wastewater using MOFs is feasible, inexpensive, and effective. Hence, our findings indicate that MOFs have a broad application in the purification of wastewater.

To facilitate progression from the laboratory to commercial applications, it will be necessary to develop facile and scalable methods to produce high-quality quantum dots (QDs) of layered two-dimensional materials (LTMs). In this paper, we for the first time report a turbulence-induced disintegration method to prepare ultra-small BN and WS2 QDs, which can easily be achieved only using a household kitchen blender to directly disintegrate their bulk counterparts in liquids. The resulting ultra-small BN and WS2 QDs exhibit excellent photoluminescence and photo-thermal converting properties, respectively. As proof-of-concept applications, these properties have great promise in cell-imaging probes and photo-thermal therapy. This work not only provides successful paradigms for preparing the QDs of other LTMs but also demonstrates potential applications for the QDs. Keywords: Turbulence-induced disintegration, BN quantum dots, WS2 quantum dots, Cell-imaging probe, Photo-thermal therapy

In this paper, multi-physical models of bending characteristics, including the static, dynamic and microwave models, are firstly proposed for the double-clamped beam switch based on flexible substrate. Both simulated and experimental verification have been carried out to prove that the changing regularity of the driving voltage and time of the switch is inversely proportional with the increase in the bending curvature of the flexible substrate. The microwave performance of the switch at the ON state is found to get worse with the increase in the bending curvature. The measured results indicate that when the bending curvature increases from 0 m−1 to 28.6 m−1, the measured driving voltage decreases from 90.0 V to 72.6 V with the error of 5.9% compared with the calculated results. The measured driving time decreases from 52.4 μs to 35.6 μs with the error of 16.7% compared with the calculated results. When the substrate bending curvature increases from 0 m−1 to 28.6 m−1, the measured reflection loss S11 of the switch gradually deteriorates from −27.1 dB to −22.0 dB with the error of 1.3 dB corresponding to the calculated results at 10 GHz. All the simulated and experimental results are consistent with the theoretical calculated results.

Aimed at improving the low measurement accuracy of the binocular vision sensor along the optical axis in the process of target tracking, we proposed a method for auxiliary correction using a laser-ranging sensor in this paper. In the process of system measurement, limited to the mechanical performance of the two-dimensional turntable, the measurement value of a laser-ranging sensor is lagged. In this paper, the lag information is updated directly to solve the time delay. Moreover, in order to give full play to the advantages of binocular vision sensors and laser-ranging sensors in target tracking, federated filtering is used to improve the information utilization and measurement accuracy and to solve the estimated correlation. The experimental results show that the real-time and measurement accuracy of the laser ranging-assisted binocular visual-tracking system is improved by the direct update algorithm and the federal filtering algorithm. The results of this paper are significant for binocular vision sensors and laser-ranging sensors in engineering applications involving target tracking systems.

Presently, piezoresistive pressure sensors are highly demanded for using in various microelectronic devices. The electrical behavior of these pressure sensor is mainly dependent on the temperature gradient. In this paper, various factors,which includes effect of temperature, doping concentration on the pressure sensitive resistance, package stress, and temperature on the Young’s modulus etc., are responsible for the temperature drift of the pressure sensor are analyzed. Based on the above analysis, an analytical calibration model of the output voltage of the sensor is proposed and the experimental data is validated through a suitable model.

In this paper, an analytical model of the composite membrane piezoresistive pressure sensor with the testing structure is established, which built the relationship between the electrostatic force and the material properties, dimension parameters of the sensor. By using the theoretical model of the sensor, it is easily to analyze the sensor’s performance, to optimize the dimension of the sensor, and to make the step of calibrating to be getting fast and accurate.

The particle dynamics model of MRFs (MRFs) is based on the discrete element technique, which takes into account essential MRF variables such as magnetic field, particle parameters, particle volume fraction, carrier fluid properties, and other parameters. Firstly, to digitally characterize the microstructure of MRFs, the particle coordination number, as a new perspective is creatively proposed. The validity and predictability of the created model are then tested in conjunction with the rheological performance studies by comparing it to the known continuous medium model. Finally, based on the proposed model, the influence of each influencing factor on the magnetorheological effect is simulated and regularity analysis is given from the perspective of particles. Linking macroscopic qualities and MRF microstructure, which offers a theoretical basis for the preparation of MRFs with improved performance and prediction of performance under various working situations. [ABSTRACT FROM AUTHOR]

The AA5052 aluminum alloy is widely used in automobile and aerospace manufacturing, and with the development of light-weight alloys, it is required that these materials exhibit better mechanical properties. Previous studies have demonstrated that the addition of Sc to aluminum alloys can improve both the microstructure and properties of the alloys. In this study, the effect of Sc on the Fe-rich phase and properties of the AA5052 aluminum alloy was studied by adding 0%, 0.05%, 0.2%, and 0.3% Sc. The results show that with the increase of Sc, the coarse needle-like Fe-rich phase gradually transforms into Chinese-script and then nearly spherical particles, reduce the size of Fe-rich phase, and refine the grain with increase of high angle grain boundaries (HAGBs). These microstructure changes enhance the strength of the AA5052 alloy through Sc addition. The ductility of the alloy is obviously improved because the addition of a lower amount of Sc changes the morphology of Fe-rich phase from needle-like into a Chinese-script, and it is subsequently reduced as a result of significant increase in HAGBs with increasing Sc content. [ABSTRACT FROM AUTHOR]