Room-Temperature Flexible CNT/Fe2O3 Film Sensor for ppb-Level H2S Detection.

Carbon nanotubes (CNTs) had room temperature response, large surface area, and excellent mechanical properties, making them favorable for the design of flexible, wearable, and portable gas sensors. However, CNTs were lacking in response and selective response to different gases, such as H2S. Here, we demonstrated a flexible H2S ppb-level gas sensor based on a carbon nanotube/amorphous Fe2O3 (CNT/Fe2O3) film at room temperature, which was fabricated via a simple one-step solvent-thermal method. The CNT/Fe2O3 film gas sensor exhibited a high selective response to H2S (with a response of 55.1% to 100 ppb H2S), rapid reversible response at room temperature (with a response time of ∼127 s to 100 ppb H2S), and low limit of detection to about 2 ppb. Additionally, the CNT/Fe2O3 film maintained good sensing performance under various bending conditions and could be further fabricated into the fiber gas sensor device via wet stretching, retaining response at the ppb level (with a response of 18.6% to 100 ppb H2S). This research on a flexible gas sensor device based on the CNT film/fiber opened up new possibilities for wearable portable electronic device applications.

A novel three traction rings device with endoscopic submucosal dissection (ESD) in the removal of a large superficial duodenal adenoma.

Endoscopic treatment is generally recommended for the duodenal epithelial adenoma. Although underwater endoscopic mucosal resection (UEMR) has become established as an effective modality for the superficial duodenal adenoma. However, it is difficult to completely remove a large superficial duodenal adenoma with en bloc resection. Endoscopic submucosal dissection (ESD) is commonly performed to remove a large superficial duodenal adenoma, whereas which is technically challenged with severe adverse events. It has reported that entire traction using clip-and-nylon ring with ESD was effective and safe in the removal of a large rectal sessile serrated adenoma (SSA). Herein, we shared our experience of the novel three traction rings device in the treatment of a large superficial duodenal adenoma.

Needs for rehabilitation in China: Estimates based on the Global Burden of Disease Study 1990-2019.

BACKGROUND: As an essential part of health services, rehabilitation is of great significance to improve the health and quality of life of the whole population. Accelerating aging calls for a significant expansion of rehabilitation services in China, but rehabilitation needs remain unclear. We conducted the study to explore the rehabilitation needs in China and project the trend of rehabilitation needs from 2020 to 2034. METHODS: The data of health conditions that might potentially benefit from rehabilitation were obtained from Global Burden of Disease (GBD) study. Estimated annual percentage changes (EAPCs) were calculated to quantify the trends of the age-standardized rates. Projections of rehabilitation needs were made until 2034 using Bayesian age-period-cohort analysis (BAPC). RESULTS: Approximately 460 million persons (33.3% of the total population) need rehabilitation in China, contributing to 63 million years lived with disabilities (YLDs) in 2019. The number of prevalent cases increased from around 268 (95% uncertainty interval [UI]: 257-282) million in 1990 to almost 460 (95% UI: 443-479) million in 2019, representing an increase of 71.3%. The highest contribution to the need for rehabilitation was musculoskeletal disorders with about 322 (95% UI: 302-343) million persons in seven aggregate disease and injury categories, and hearing loss with over 95 (95% UI: 84-107) million people among 25 health conditions. Based on the projection results, there will be almost 636 million people (45% of the total population) needing rehabilitation services in China by 2034, representing an increase of 38.3%. The rehabilitation needs of neoplasms, cardiovascular diseases, and neurological disorders are expected to increase significantly from 2019 to 2034, with increases of 102.3%, 88.8% and 73.2%, respectively. CONCLUSIONS: The need for rehabilitation in China substantially increased over the last 30 years. It is predicted that over two in five people will require rehabilitation by 2034, thus suggesting the need to develop rehabilitation services that meet individuals' rehabilitation needs.

Risk factor differences in five-year progression of Intracranial artery stenosis and cerebral small vessel disease in general population.

BACKGROUND: Intracranial artery stenosis (ICAS) and cerebral small vessel disease (CSVD) are associated with a heavy socioeconomic burden; however, their longitudinal changes remain controversial. METHODS: We conducted a longitudinal analysis on 756 participants of Shunyi Cohort who underwent both baseline and follow-up brain magnetic resonance imaging (MRI) and MR angiography in order to investigate the risk factors for ICAS and CSVD progression in community population. Incident ICAS was defined as new stenosis occurring in at least one artery or increased severity of the original artery stenosis. CSVD markers included lacunes, cerebral microbleeds (CMB), and white matter hyperintensities (WMH). RESULTS: After 5.58 ± 0.49 years of follow-up, 8.5% of the 756 participants (53.7 ± 8.0 years old, 65.1% women) had incident ICAS. Body mass index (BMI) (OR = 1.09, 95% CI = 1.01-1.17, p = 0.035) and diabetes mellitus (OR = 2.67, 95% CI = 1.44-4.93, p = 0.002) were independent risk factors for incident ICAS. Hypertension was an independent risk factor for incident lacunes (OR = 2.12, 95% CI = 1.20-3.77, p = 0.010) and CMB (OR = 2.32, 95% CI = 1.22-4.41, p = 0.011), while WMH progression was primarily affected by BMI (ß = 0.108, SE = 0.006, p = 0.002). A higher LDL cholesterol level was found to independently protect against WMH progression (ß = -0.076, SE = 0.027, p = 0.019). CONCLUSIONS: Modifiable risk factor profiles exhibit different in patients with ICAS and CSVD progression. Controlling BMI and diabetes mellitus may help to prevent incident ICAS, and antihypertensive therapy may conduce to mitigate lacunes and CMB progression. LDL cholesterol may play an inverse role in large arteries and small vessels.

Identification of novel broad-spectrum antiviral drugs targeting the N-terminal domain of the FIPV nucleocapsid protein.

Coronaviruses pose serious threats to human and animal health worldwide, of which their structural nucleocapsid (N) proteins play multiple key roles in viral replication. However, the structures of animal coronavirus N proteins are poorly understood, posing challenges for research on their functions and pathogenic mechanisms as well as the development of N protein-based antiviral drugs. Therefore, N proteins must be further explored as potential antiviral targets. We determined the structure of the NNTD of feline infectious peritonitis virus (FIPV) and identified 3,6-dihydroxyflavone (3,6- DHF) as an effective N protein inhibitor. 3,6-DHF successfully inhibited FIPV replication in CRFK cells, showing broad-spectrum activity and effectiveness against drugresistant strains. Our study provides important insights for developing novel broadspectrum anti-coronavirus drugs and treating infections caused by drug-resistant mutant strains.

Genomic profiling of colorectal cancer in large-scale Chinese patients: amplification and somatic mutations in ERBB2.

Objectives: Human epidermal growth factor receptor 2 (HER2)-targeted therapies have demonstrated potential benefits for metastatic colorectal cancer (mCRC) patients with HER2 amplification, but are not satisfactory in cases of HER2 mutant CRCs. Methods: Consequently, further elucidation of amplifications and somatic mutations in erythroblastic oncogene B-2 (ERBB2) is imperative. Comprehensive genomic profiling was conducted on 2454 Chinese CRC cases to evaluate genomic alterations in 733 cancer-related genes, tumor mutational burden, microsatellite instability, and programmed death ligand 1 (PD-L1) expression. Results: Among 2454 CRC patients, 85 cases (3.46%) exhibited ERBB2 amplification, and 55 cases (2.24%) carried ERBB2 mutation. p.R678Q (28%), p.V8421 (24%), and p.S310F/Y (12%) were the most prevalent of the 16 detected mutation sites. In comparison to the ERBB2 altered (alt) group, KRAS/BRAF mutations were more prevalent in ERBB2 wild-type (wt) samples (ERBB2wt vs. ERBB2alt, KRAS: 50.9% vs. 25.6%, p < 0.05; BRAF: 8.5% vs. 2.3%, p < 0.05). 32.7% (18/55) of CRCs with ERBB2 mutation exhibited microsatellite instability high (MSI-H), while no cases with HER2 amplification displayed MSI-H. Mutant genes varied between ERBB2 copy number variation (CNV) and ERBB2 single nucleotide variant (SNV); TP53 alterations tended to co-occur with ERBB2 amplification (92.3%) as opposed to ERBB2 mutation (58.3%). KRAS and PIK3CA alterations were more prevalent in ERBB2 SNV cases (KRAS/PIK3CA: 45.8%/31.2%) compared to ERBB2 amplification cases (KRAS/PIK3CA: 14.1%/7.7%). Conclusion: Our study delineates the landscape of HER2 alterations in a large-scale cohort of CRC patients from China. These findings enhance our understanding of the molecular features of Chinese CRC patients and offer valuable implications for further investigation.

Density functional theory-based study on the structural, electronic and spectral properties of gas-phase PbMg n - (n = 2-12) clusters.

Gas-phase PbMg n- (n = 2-12) cluster structures were globally searched on their potential energy surfaces by means of the CALYPSO prediction software. Structural optimization and calculations of properties such as relative energy and electronic structure were then carried out by density functional theory for each size of low energy isomer. The structural, relative stability, natural charge population, natural electronic configuration and distribution of the strongest peaks of the infrared and Raman spectra of the low energy isomers of PbMg n- (n = 2-12) clusters were systematically investigated in the present work. It was shown that the PbMg7- cluster ground state isomer exhibits the highest stability, for which special electronic excitation and chemical bonding analyses were performed. It is reasonable to believe that this work enriches the structural, spectroscopic and other data of magnesium-based clusters and provides some theoretical basis for possible future experimental syntheses.

Association of unsweetened and sweetened cereal consumption with all-cause and cause-specific mortality: a large prospective population-based cohort study.

Background & aims: Although previous observational studies have suggested an association between whole grain consumption (including breakfast cereals) and a reduced risk of death, no study has explored in detail the association between consumption of cereal with or without added sweeteners and death. We therefore aimed to evaluate the association between unsweetened, sugar-sweetened, and artificially sweetened cereals and all-cause and cause-specific mortality. Methods: We conducted a prospective cohort study of 186 419 UK Biobank participants who met the inclusion criteria for this study. Participants with baseline demographic, lifestyle, dietary, and clinical data were recruited from 2006 to 2010 and followed up until 2023. The intake of unsweetened, sugar-sweetened, or artificially sweetened cereals was estimated through repeated 24 hour dietary recalls. The non-linear relationships between daily dosage of cereal and all-cause, cancer-specific, and cardiovascular disease (CVD)-specific mortality were calculated using a restricted cubic spline curve. Hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality were calculated using Cox regression models. Results: During a median follow-up of 13.6 years, 11 351 all-cause deaths were recorded, including 6176 cancer deaths and 2126 CVD deaths. Cox regression models with restricted cubic splines showed a non-linear association between unsweetened cereals and all-cause and cancer-specific mortality. Compared with non-consumers, consumers of different amounts of unsweetened cereals (0 to 0.5, 0.5 to 1.5, and >1.5 bowls per day) had lower risks of all-cause mortality in the multivariate Cox models, with respective HRs of 0.89 (95%CI: 0.84-0.95), 0.90 (95%CI: 0.86-0.94), and 0.89 (95%CI: 0.82-0.97). However, no association was observed between consumption of sugar or artificially sweetened cereals and the risk of mortality. When cereals were divided into those with or without dried fruit, the findings were consistent with our primary results. Conclusions: Moderate consumption of unsweetened cereals was associated with a reduced risk of all-cause mortality, suggesting caution in consuming cereals with added sugar or artificial sweeteners.

Deep insights into the assembly mechanisms, co-occurrence patterns, and functional roles of microbial community in wastewater treatment plants.

The understanding of activated sludge microbial status and roles is imperative for improving and enhancing the performance of wastewater treatment plants (WWTPs). In this study, we conducted a deep analysis of activated sludge microbial communities across five compartments (inflow, effluent, and aerobic, anoxic, anaerobic tanks) over temporal scales, employing high-throughput sequencing of 16S rRNA amplicons and metagenome data. Clearly discernible seasonal patterns, exhibiting cyclic variations, were observed in microbial diversity, assembly, co-occurrence network, and metabolic functions. Notably, summer samples exhibited higher α-diversity and were distinctly separated from winter samples. Our analysis revealed that microbial community assembly is influenced by both stochastic processes (66%) and deterministic processes (34%), with winter samples demonstrating more random assembly compared to summer. Co-occurrence patterns were predominantly mutualistic, with over 96% positive correlations, and summer networks were more organized than those in winter. These variations were significantly correlated with temperature, total phosphorus and sludge volume index. However, no significant differences were found among microbial community across five compartments in terms of ß diversity. A core community of keystone taxa was identified, playing key roles in eight nitrogen and eleven phosphorus cycling pathways. Understanding the assembly mechanisms, co-occurrence patterns, and functional roles of microbial communities is essential for the design and optimization of biotechnological treatment processes in WWTPs.

[Simulation and Analysis of Ozone Pollution Process in Shijiazhuang Based on CMAQ-ISAM Model].

In Shijiazhuang City, ozone （O3） pollution occurs frequently in June every year. In June 2023, the average O3 8 h concentration （O3-8h） pollution exceeded 80% of the days in the month, and O3 was the primary pollutant, accounting for 100%. For an O3 heavy pollution process from June 11 to 18, the air quality model WRF-CMAQ was used for simulation, and the average error data MFB and MFE were -10.47% and 17.96%, respectively, which was within the ideal error range. The CMAQ process analysis module was used to simulate the physical and chemical processes in Shijiazhuang City, and the dry deposition （DDEP） contribution concentration was -23.88 µg·m-3, which was the main process of O3 consumption, whereas the transport process （TRAN） was the main source of O3, among which the contribution was more significant in vertical transport （VTRA）. At the same time, the source analysis module （ISAM） was used to analyze the O3 contribution of local and surrounding areas in Shijiazhuang City. The results showed that the contribution rate of local industry sources in Shijiazhuang City was as follows： traffic source （12.54%） > industrial source （6.94%） > residential source （6.56%） > power source （4.75%）. The long-distance transmission source （BCON） continued to be in the first place with a high contribution rate of 63.31%. In the heavy pollution period under stable weather, the contribution concentration of BCON in the D02 layer of the nested domain to Shijiazhuang City was lower than the sum of the marked area. Among the surrounding cities, Baoding City had the highest contribution rate under stable weather, accounting for 26.21%. In the late period, the contribution concentration of Xingtai City increased rapidly under the action of high-value southwest wind. To effectively reduce O3 pollution, it is necessary to reduce emissions in the city and to control the upwind cities in advance, and the implementation of inter-regional joint prevention and control is the key.

Cyanobacterial blooms management: A simulation-based optimization method.

Controlling cyanobacterial blooms is not only an engineering and technical issue but also an optimization problem in environment management. Under budget constraints, a novel simulation-based optimization model for cyanobacterial control is constructed in this study. The simulation model is used for simulating cyanobacteria growth and diffusion processes. The optimization model is utilized to determine the optimal search and treatment path. Through the interactive coupling of simulation modeling and resource allocation optimization, this research provides decision-makers with new operational guidelines for cyanobacterial control. Our test results demonstrate that the initial invasion frequency has a greater economic impact than invasion abundance. The nearby cells to the initial invasion are affected first, and then the influence radiates outward in a diffusion pattern. Using a slow search speed and a treatment frequency of every 10 days can achieve the lowest possible economic losses in most test scenarios. Moreover, we also find that the optimal search and treatment paths revolve around the initial invasion location. This study is a typical interdisciplinary research, which can assist water resource managers in making more accurate decisions regarding cyanobacteria removal paths, removal frequencies, and treatment speeds.

Strong and Fatigue-Resistant Carbon Nanotube Composites Enabled by Amorphous/Crystalline Heterophase Shell.

Lightweight materials with high strength and long cyclic lifespan are greatly demanded in practical applications, yet these properties are usually mutually exclusive. Here, we present a strong, lightweight, highly deformation-tolerant, and fatigue-resistant carbon nanotube (CNT) composite enabled by an amorphous/crystalline heterophase carbon shell. In particular, we obtain nanocrystallites with CNT-induced crystalline orientation uniformly embedded within an amorphous matrix by controlled thermal annealing. The heterophase carbon shell effectively alleviates the stress concentration and inhibits crack propagation, which renders our composite superior mechanical properties and high fatigue resistance (106 compression cycles at 20% strain with high stress of 144 kPa, or 5 × 105 cycles at 50% strain with stress up to 260 kPa). This study provides a deep understanding of amorphous-crystalline phase transition and insight into utilizing phase engineering to design and develop other high-performance functional materials such as structural materials and catalysis.

Phenotypes Associated with NOTCH3 Cysteine-Sparing Mutations in Patients with Clinical Suspicion of CADASIL: A Systematic Review.

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is caused by NOTCH3 mutations affecting the number of cysteines. The pathogenic role of cysteine-sparing NOTCH3 mutations with typical clinical CADASIL syndrome is still debated. This review aimed to characterize NOTCH3 cysteine-sparing mutations in patients with clinical suspicion of CADASIL. Articles on NOTCH3 cysteine-sparing mutations with clinical suspicion of CADASIL were reviewed. Clinical and radiological cerebral phenotypes data were extracted and characterized across regions and compared with phenotypes of typical CADASIL patients. We screened 298 NOTCH3 cysteine-sparing mutation individuals from 20 publications, and mutations in exon 3 were the most frequently reported (21.46%). Gait impairment (76.47%), cognitive impairment (67.47%), and stroke (62.37%) were the three most common clinical phenotypes; the most frequent radiological cerebral phenotypes were lacunes (74.29%) and cerebral microbleeds (72.73%). Compared with CADASIL patients, cognitive impairment and cerebral microbleed frequencies were significantly higher in patients with NOTCH3 cysteine-sparing mutations, while the white matter hyperintensities in anterior temporal polar and external capsule were rarely observed. Compared with Western patients, radiological phenotypes were more common than clinical phenotypes in cysteine-sparing Asian patients. More than half of cysteine-sparing patients had positive granular osmiophilic material deposits. NOTCH3 cysteine-sparing mutations in patients with clinical suspicion of CADASIL mainly manifested with gait and cognitive impairment but rare white matter hyperintensities in anterior temporal pole and external capsule. Further studies are warranted to pay attention to atypical NOTCH3 variants, which could guide specific diagnosis and help unravel underlying mechanisms.

Correlation between Circle of Willis configuration and intracranial arterial dolichoectasia, and genetic contributions.

OBJECTIVES: Intracranial arterial dolichoectasia (IADE) is characterized by the dilation, elongation, and tortuosity of intracranial arteries. We aimed to investigate the association between variations of the Circle of Willis (COW) and IADE in the general population, as well as estimate the genetic correlation between COW variations and IADE. METHODS: A total of 981 individuals from a population-based cohort were included. Brain magnetic resonance angiography was performed to assess COW variants and measure the diameters of intracranial arteries. IADE was defined as a total intracranial volume-adjusted diameter ≥ 2 standard deviations. Logistic regression models were used to analyze the association between COW variations and IADE. The heritability and genetic correlation were estimated using genome-wide complex trait analysis (GCTA) based on single nucleotide polymorphism (SNP) array data. RESULTS: The prevalence of IADE was 6.2 %. Hypoplastic/absent A1 segments were associated with an increase in contralateral ICA diameter (ß ± SE, 0.279 ± 0.049; p = 0.001) and a decrease in ipsilateral ICA diameter (ß ± SE, -0.300 ± 0.050; p = 0.001). Fetal-type posterior cerebral artery (FTP) was associated with a larger ICA diameter (ß ± SE, 0.326 ± 0.048; p = 0.001) and a smaller BA diameter (ß ± SE, -0.662 ± 0.043; p = 0.001). FTP revealed a positive genetic correlation with ICA dilation (rG = 0.259 ± 0.175; p = 0.0009) and a negative genetic correlation with BA dilation (rG = -0.192 ± 0.153, p = 0.015). CONCLUSIONS: There was an association between COW variations and larger intracranial arterial diameters in the general population. Genetic factors may play a role in the development of intracranial arterial dilation and the formation of COW variants.

High-Strength, Antiswelling Directional Layered PVA/MXene Hydrogel for Wearable Devices and Underwater Sensing.

Hydrogel sensors are widely utilized in soft robotics and tissue engineering due to their excellent mechanical properties and biocompatibility. However, in high-water environments, traditional hydrogels can experience significant swelling, leading to decreased mechanical and electrical performance, potentially losing shape, and sensing capabilities. This study addresses these challenges by leveraging the Hofmeister effect, coupled with directional freezing and salting-out techniques, to develop a layered, high-strength, tough, and antiswelling PVA/MXene hydrogel. In particular, the salting-out process enhances the self-entanglement of PVA, resulting in an S-PM hydrogel with a tensile strength of up to 2.87 MPa. Furthermore, the S-PM hydrogel retains its structure and strength after 7 d of swelling, with only a 6% change in resistance. Importantly, its sensing performance is improved postswelling, a capability rarely achievable in traditional hydrogels. Moreover, the S-PM hydrogel demonstrates faster response times and more stable resistance change rates in underwater tests, making it crucial for long-term continuous monitoring in challenging aquatic environments, ensuring sustained operation and monitoring.

Molecular cloning and functional characterization of mitochondrial RNA splicing 2 in fish Megalobrama amblycephala, and its potential roles in magnesium homeostasis and mitochondrial function.

Mitochondrial function can be regulated by ion channels. Mitochondrial RNA splicing 2 (Mrs2) is a magnesium ion (Mg2+) channel located in the inner mitochondrial membrane, thereby mediating the Mg2+ influx into the mitochondrial matrix. However, its potential role in regulating the Mg homeostasis and mitochondrial function in aquatic species is still unclear. This study molecularly characterizes the gene encoding Mrs2 in fish M. amblycephala with its functions in maintaining the Mg homeostasis and mitochondrial function verified. The mrs2 gene is 2133 bp long incorporating a 1269 bp open reading frame, which encodes 422 amino acids. The Mrs2 protein includes two transmembrane domains and a conserved tripeptide Gly-Met-Asn, and has a high homology (65.92-97.64%) with those of most vertebrates. The transcript of mrs2 was relatively high in the white muscle, liver and kidney. The inhibition of mrs2 reduces the expressions of Mg2+ influx/efflux-related proteins, mitochondrial Mg content, and the activities of mitochondrial complex I and V in hepatocytes. However, the over-expression of mrs2 increases the expressions of Mg2+ influx/efflux-related proteins, mitochondrial Mg content, and the complex V activity, but decreases the activities of mitochondrial complex III and IV and citrate synthase in hepatocytes. Collectively, Mrs2 is highly conserved among different species, and is prerequisite for maintaining Mg homeostasis and mitochondrial function in fish.

Early detection of multiple endocrine neoplasia type 1: A case report.

BACKGROUND: Multiple endocrine neoplasias (MENs) are a group of hereditary diseases involving multiple endocrine glands, and their prevalence is low. MEN type 1 (MEN1) has diverse clinical manifestations, mainly involving the parathyroid glands, gastrointestinal tract, pancreas and pituitary gland, making it easy to miss the clinical diagnosis. CASE SUMMARY: We present the case of a patient in whom MEN1 was detected early. A middle-aged male with recurrent abdominal pain and diarrhea was admitted to the hospital. Blood tests at admission revealed hypercalcemia and hypophosphatemia, and emission computed tomography of the parathyroid glands revealed a hyperfunctioning parathyroid lesion. Gastroscopy findings suggested a duodenal bulge and ulceration. Ultrasound endoscopy revealed a hypoechoic lesion in the duodenal bulb. Further blood tests revealed elevated levels of serum gastrin. Surgery was performed, and pathological analysis of the surgical specimens revealed a parathyroid adenoma after parathyroidectomy and a neuroendocrine tumor after duodenal bulbectomy. The time from onset to the definitive diagnosis of MEN1 was only approximately 1 year. CONCLUSION: For patients who present with gastrointestinal symptoms accompanied by hypercalcemia and hypophosphatemia, clinicians need to be alert to the possibility of MEN1.

Mass spectrometry imaging as a promising analytical technique for herbal medicines: an updated review.

Herbal medicines (HMs) have long played a pivotal role in preventing and treating various human diseases and have been studied widely. However, the complexities present in HM metabolites and their unclear mechanisms of action have posed significant challenges in the modernization of traditional Chinese medicine (TCM). Over the past two decades, mass spectrometry imaging (MSI) has garnered increasing attention as a robust analytical technique that enables the simultaneous execution of qualitative, quantitative, and localization analyses without complex sample pretreatment. With advances in technical solutions, MSI has been extensively applied in the field of HMs. MSI, a label-free ion imaging technique can comprehensively map the spatial distribution of HM metabolites in plant native tissues, thereby facilitating the effective quality control of HMs. Furthermore, the spatial dimension information of small molecule endogenous metabolites within animal tissues provided by MSI can also serve as a supplement to uncover pharmacological and toxicological mechanisms of HMs. In the review, we provide an overview of the three most common MSI techniques. In addition, representative applications in HM are highlighted. Finally, we discuss the current challenges and propose several potential solutions. We hope that the summary of recent findings will contribute to the application of MSI in exploring metabolites and mechanisms of action of HMs.

Wet-Spinning Carbon Nanotube/Shape Memory Polymer Composite Fibers with High Actuation Stress and Predesigned Shape Change.

Actuators based on shape memory polymers and composites incorporating nanomaterial additives have been extensively studied; achieving both high output stress and precise shape change by low-cost, scalable methods is a long-term-desired yet challenging task. Here, conventional polymers (polyurea) and carbon nanotube (CNT) fillers are combined to fabricate reinforced composite fibers with exceptional actuation performance, by a wet-spinning method amenable for continuous production. It is found that a thermal-induced shrinkage step could obtain densified strong fibers, and the presence of CNTs effectively promotes the tensile orientation of polymer molecular chains, leading to much improved mechanical properties. Consequently, the CNT/ polyurea composite fibers exhibit stresses as high as 33 MPa within 0.36 s during thermal actuation, and stresses up to 22 MPa upon electrical stimulation enabled by the built-in conductive CNT networks. Utilizing the flexible thin fibers, various shape change behavior are also demonstrated including the conversion between different structures/curvatures, and recovery of predefined simple patterns. This high-performance composite fibers, capable of both thermal and electrical actuation and produced by low-cost materials and fabrication process, may find many potential applications in wearable devices, robotics, and biomedical areas.

Genome-Wide Mendelian Randomization Study Reveals Druggable Genes for Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease (CSVD) is a group of neurological disorders that affect the small blood vessels within the brain, for which no effective treatments are currently available. We conducted a Mendelian randomization (MR) study to identify candidate therapeutic genes for CSVD. METHODS: We retrieved genome-wide association study data from 6 recently conducted, extensive investigations focusing on CSVD magnetic resonance imaging markers and performed a 2-sample MR analysis to assess the potential causal effects of gene expression and protein level within druggable genes on CSVD in blood and brain tissues. Colocalization analyses and repeat studies were undertaken to verify the relationship. Additionally, mediation analysis was conducted to explore the potential mechanisms involving druggable genes and known risk factors for CSVD. Finally, phenome-wide MR analyses were applied to evaluate the potential adverse effects related to the identified druggable genes for CSVD treatment. RESULTS: Overall, 5 druggable genes consistently showed associations with CSVD in MR analyses across both the discovery and validation cohorts. Notably, the ALDH2 and KLHL24 genes were identified as associated with CSVD in both blood and brain tissues, whereas the genes ADRB1, BTN3A2, and EFEMP1 were exclusively detected in brain tissue. Moreover, mediation analysis elucidated the proportion of the total effects mediated by CSVD risk factors through candidate druggable genes, which ranged from 5.5% to 18.5%, and offered potential explanations for the observed results. A comprehensive phenome-wide MR analysis further emphasized both the therapeutic benefits and potential side effects of targeting these candidate druggable genes. CONCLUSIONS: This study provides genetic evidence supporting the potential therapeutic benefits of targeting druggable genes for treating CSVD, which will be useful for prioritizing CSVD drug development.