Chromosome-level genome assembly of the western flower thrips Frankliniella occidentalis.

The western flower thrips Frankliniella occidentalis (Thysanoptera: Thripidae) is a global invasive species that causes increasing damage by direct feeding on crops and transmission of plant viruses. Here, we assemble a previously published scaffold-level genome into a chromosomal level using Hi-C sequencing technology. The assembled genome has a size of 302.58 Mb, with a contig N50 of 1533 bp, scaffold N50 of 19.071 Mb, and BUSCO completeness of 97.8%. All contigs are anchored on 15 chromosomes. A total of 16,312 protein-coding genes are annotated in the genome with a BUSCO completeness of 95.2%. The genome contains 492 non-coding RNA, and 0.41% of interspersed repeats. In conclusion, this high-quality genome provides a convenient and high-quality resource for understanding the ecology, genetics, and evolution of thrips.

Drug-target interaction predictions with multi-view similarity network fusion strategy and deep interactive attention mechanism.

MOTIVATION: Accurately identifying the drug-target interactions (DTIs) is one of the crucial steps in the drug discovery and drug repositioning process. Currently, many computational-based models have already been proposed for DTI prediction and achieved some significant improvement. However, these approaches pay little attention to fuse the multi-view similarity networks related to drugs and targets in an appropriate way. Besides, how to fully incorporate the known interaction relationships to accurately represent drugs and targets is not well investigated. Therefore, there is still a need to improve the accuracy of DTI prediction models. RESULTS: In this study, we propose a novel approach that employs Multi-view similarity network fusion strategy and deep Interactive attention mechanism to predict Drug-Target Interactions (MIDTI). First, MIDTI constructs multi-view similarity networks of drugs and targets with their diverse information and integrates these similarity networks effectively in an unsupervised manner. Then, MIDTI obtains the embeddings of drugs and targets from multi-type networks simultaneously. After that, MIDTI adopts the deep interactive attention mechanism to further learn their discriminative embeddings comprehensively with the known DTI relationships. Finally, we feed the learned representations of drugs and targets to the multilayer perceptron (MLP) model and predict the underlying interactions. Extensive results indicate that MIDTI significantly outperforms other baseline methods on the DTI prediction task. The results of the ablation experiments also confirm the effectiveness of the attention mechanism in the multi-view similarity network fusion strategy and the deep interactive attention mechanism. AVAILABILITY: https://github.com/XuLew/MIDTI. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Development and validation of a nomogram for predicting heterotopic ossification following spinal cord injury.

OBJECTIVE: Heterotopic ossification (HO) following spinal cord injury (SCI) can severely compromise patient mobility and quality of life. Precise identification of SCI patients at an elevated risk for HO is crucial for implementing early clinical interventions. While the literature presents diverse correlations between HO onset and purported risk factors, the development of a predictive model to quantify these risks is likely to bolster preventive approaches. This study is designed to develop and validate a nomogram-based predictive model that estimates the likelihood of HO in SCI patients, utilizing recognized risk factors to expedite clinical decision-making processes. METHODS: We recruited a total of 145 patients with SCI and presenting with HO who were hospitalized at the China Rehabilitation Research Center, Beijing Boai Hospital, from June 2016 to December 2022. Additionally, 337 patients with SCI without HO were included as controls. Comprehensive data were collected for all study participants, and subsequently, the dataset was randomly partitioned into training and validation groups. Using Least Absolute Shrinkage and Selection Operator regression, variables were meticulously screened during the pretreatment phase to formulate the predictive model. The efficacy of the model was then assessed using metrics including receiver-operating characteristic (ROC) analysis, calibration assessment, and decision curve analysis. RESULTS: The final prediction model incorporated age, sex, complete spinal cord injury status, spasm occurrence, and presence of deep vein thrombosis (DVT). Notably, the model exhibited commendable performance in both the training and validation groups, as evidenced by areas under the ROC curve (AUCs) of 0.756 and 0.738, respectively. These values surpassed the AUCs obtained for single variables, namely age (0.636), sex (0.589), complete spinal cord injury (0.681), spasm occurrence (0.563), and DVT presence (0.590). Furthermore, the calibration curve illustrated a congruence between the predicted and actual outcomes, indicating the high accuracy of the model. The decision curve analysis indicated substantial net benefits associated with the application of the model, thereby underscoring its practical utility. CONCLUSIONS: HO following SCI correlates with several identifiable risk factors, including male gender, youthful age, complete SCI, spasm occurrence and DVT. Our predictive model effectively estimates the likelihood of HO development by leveraging these factors, assisting physicians in identifying patients at high risk. Subsequently, correct positioning to prevent spasm-related deformities and educating healthcare providers on safe lower limb mobilization techniques are crucial to minimize muscle injury risks from rapid iliopsoas muscle extension. Additionally, the importance of early DVT prevention through routine screening and anticoagulation is emphasized to further reduce the incidence of HO.

Comprehensive next-generation sequencing identifies novel putative pathogenic or likely pathogenic germline variants in patients with concurrent tubo-ovarian and endometrial serous and endometrioid carcinomas or precursors.

BACKGROUND: Endometrial serous carcinoma (ESC) and tubo-ovarian high-grade serous carcinoma (HGSC) are characterized by late-stage presentation and high mortality. Current guidelines for prevention recommend risk-reducing salpingo-oophorectomy (RRSO) in patients with hereditary mutations in cancer susceptibility genes. However, HGSC displays extensive genetic heterogeneity with alterations in 168 genes identified in TCGA study, but current germline testing panels are often limited to the handful of recurrently mutated genes, leaving families with rare hereditary gene mutations potentially at-risk. OBJECTIVE: To determine if there are rare germline mutations that may aid in early identification of more patients at-risk for ESC and/or HGSC by evaluating patients with concurrent ESC, HGSC or precursor lesions, and endometrial atypical hyperplasia (CAH) or low-grade endometrial endometrioid adenocarcinoma (LGEEA). METHODS: We performed targeted next-generation sequencing using TSO 500, a 523 gene panel, on formalin-fixed paraffin-embedded tumor and matched benign non-tumor tissue blocks from 5 patients with concurrent ESC, HGSC or precursor lesions, and CAH or LGEEA. RESULTS: We identified germline pathogenic, likely pathogenic or uncertain significance variants in cancer susceptibility genes in 4 of 5 patients - affected genes included GLI1, PIK3R1, FOXP1, FANCD2, INPP4B and H3F3C. Notably, none of these genes were included in the commercially available germline testing panels initially used to evaluate the patients at the time of their diagnoses. CONCLUSION: Comprehensive germline testing of patients with concurrent LGEEA or CAH and ESC, HGSC or precursor lesions may aid in early identification of relatives at-risk for cancer who may be candidates for RRSO with hysterectomy.

Mouse brain elastography changes with sleep/wake cycles, aging, and Alzheimer's disease.

Understanding the physiological processes in aging and how neurodegenerative disorders affect cognitive function is a high priority for advancing human health. One specific area of recently enabled research is the in vivo biomechanical state of the brain. This study utilized reverberant optical coherence elastography, a high-resolution elasticity imaging method, to investigate stiffness changes during the sleep/wake cycle, aging, and Alzheimer's disease in murine models. Four-dimensional scans of 44 wildtype mice, 13 mice with deletion of aquaporin-4 water channel, and 12 mice with Alzheimer-related pathology (APP/PS1) demonstrated that (1) cortical tissue became softer (on the order of a 10% decrease in shear wave speed) when young wildtype mice transitioned from wake to anesthetized, yet this effect was lost in aging and with mice overexpressing amyloid-ß or lacking the water channel AQP4. (2) Cortical stiffness increased with age in all mice lines, but wildtype mice exhibited the most prominent changes as a function of aging. The study provides novel insight into the brain's biomechanics, the constraints of fluid flow, and how the state of brain activity affects basic properties of cortical tissues.

Sensitivity-Enhancing Strategies of Graphene Field-Effect Transistor Biosensors for Biomarker Detection.

The ultrasensitive recognition of biomarkers plays a crucial role in the precise diagnosis of diseases. Graphene-based field-effect transistors (GFET) are considered the most promising devices among the next generation of biosensors. GFET biosensors possess distinct advantages, including label-free, ease of integration and operation, and the ability to directly detect biomarkers in liquid environments. This review summarized recent advances in GFET biosensors for biomarker detection, with a focus on interface functionalization. Various sensitivity-enhancing strategies have been overviewed for GFET biosensors, from the perspective of optimizing graphene synthesis and transfer methods, refinement of surface functionalization strategies for the channel layer and gate electrode, design of biorecognition elements and reduction of nonspecific adsorption. Further, this review extensively explores GFET biosensors functionalized with antibodies, aptamers, and enzymes. It delves into sensitivity-enhancing strategies employed in the detection of biomarkers for various diseases (such as cancer, cardiovascular diseases, neurodegenerative disorders, infectious viruses, etc.) along with their application in integrated microfluidic systems. Finally, the issues and challenges in strategies for the modulation of biosensing interfaces are faced by GFET biosensors in detecting biomarkers.

Children with developmental coordination disorders: a review of approaches to assessment and intervention.

Developmental Coordination Disorder (DCD) is a neurodevelopmental disorder characterized by deficits in motor skills, with gross and fine motor dysfunction being the main symptom. This condition greatly impairs children's daily life, learning, and social interaction. Symptoms typically appear during preschool or school age, and if left untreated, they can persist into adulthood. Thus, early assessment and intervention are crucial to improve the prognosis. This study aims to review the existing literature on DCD, providing a comprehensive overview of the assessment for children with DCD in terms of body functions and structures, activities and participation, and environmental factors within the framework of the International Classification of Functioning, Disability, and Health - Children and Youth (ICF-CY). Additionally, specific rehabilitation interventions will be described, offering valuable insights for the clinical assessment and intervention of children with DCD.

Mechanism-Guided Computational Design Drives meso-Diaminopimelate Dehydrogenase to Efficient Synthesis of Aromatic d-amino Acids.

Aromatic d-amino acids (d-AAs) play a pivotal role as important chiral building blocks and key intermediates in fine chemical and drug synthesis. Meso-diaminopimelate dehydrogenase (DAPDH) serves as an excellent biocatalyst in the synthesis of d-AAs and their derivatives. However, its strict substrate specificity and the lack of efficient engineering methods have hindered its widespread application. Therefore, this study aims to elucidate the catalytic mechanism underlying DAPDH from Proteus vulgaris (PvDAPDH) through the examination of its crystallographic structure, computational simulations of potential energies and molecular dynamics simulations, and site-directed mutagenesis. Mechanism-guided computational design showed that the optimal mutant PvDAPDH-M3 increased specific activity and catalytic efficiency (kcat/Km) for aromatic keto acids up to 124-fold and 92.4-fold, respectively, compared to that of the wild type. Additionally, it expanded the substrate scope to 10 aromatic keto acid substrates. Finally, six high-value-added aromatic d-AAs and their derivatives were synthesized using a one-pot three-enzyme cascade reaction, exhibiting a good conversion rate ranging from 32 to 84% and excellent stereoselectivity (enantiomeric excess >99%). These findings provide a potential synthetic pathway for the green industrial production of aromatic d-AAs.

Association between sugar-sweetened beverages and duration of physical exercise with psychological symptoms among Tibetan university students at high altitude.

Background: Sugar-sweetened beverages (SSBs) and duration of physical exercise are strongly associated with physical health. Unfortunately, there are few studies focused on the association with psychological symptoms, let alone Tibetan university students at high altitudes in China. Methods: A stratified cluster sampling method was used to include 8,268 Tibetan university students aged 19-22 years in Qinghai and Tibet, both of which are high-altitude regions of China. Self-assessment questionnaires on SSBs, duration of physical exercise, and psychological symptoms were administered. The chi-square test and logistic regression analysis were used to analyze the associations among them. Results: The detection rate of psychological symptoms among Tibetan university students in high-altitude areas of China was 16.7%, with in girls (18.2%) higher than that in boys (14.8%), and the difference was statistically significant (χ2 = 11.73, p < 0.01). The proportion of SSBs for university students ≤1 time/week, 2-5 times/week, and ≥ 6 times/week were 54.2, 24.3, and 21.5%, respectively. The proportion of duration of physical exercise for >60 min/d was only 5.4%. Logistic regression analysis showed that compared with the SSBs ≤1 time/week group of university students, SSBs 2-5 times/week (OR = 1.45, 95% CI: 1.24-1.70) and ≥ 6 times/week (OR = 3.06, 95% CI: 2.62-3.57) had an increased risk of psychological symptoms (p < 0.001). In the reference group, the risk of psychological symptoms was also significantly increased in the group of university students with duration of physical exercise >60 min/d (OR = 2.08, 95% CI: 1.48-2.93), and the risk of psychological symptoms was also significantly increased in the group with duration of physical exercise <30 min/d (OR = 2.08, 95% CI: 1.48-2.93). The risk of psychological symptoms was also significantly increased in the university students with the duration of physical exercise <30 min/d (OR = 2.08, 95% CI: 1.48 ~ 2.93) group. Conclusion: SSBs and exercise time may be important influences on the psychological symptoms of Tibetan university students at high altitudes in China. This study has important implications for mental health planning in universities in highland areas and may also provide guidance for mental health interventions for Tibetan university students.

miRNAs Influence m6A RNA Methylation through FTO and IGF2BP2 in Pressure Overload-Induced Heart Failure.

BACKGROUND: N6-adenosine methylation (m6A) is a prevalent RNA modification associated with heart failure, alongside aberrant miRNA expression. Despite indications of miRNAs regulating m6A modification, their specific influence on m6A in heart failure remains unclear. METHODS: The initial analysis utilized transcriptome and methylation sequencing data from GSE131296 in mice to identify key m6A methylation enzymes in heart failure and construct an associated network. Integration of miRNA sequencing data from GSE231700 revealed miRNAs influencing m6A methylation enzymes, contributing to the formation of a comprehensive network. Furthermore, differential miRNA levels in human serum were assessed via qPCR, and the expression of m6A methyltransferases in the heart was confirmed using proteomic databases. RESULTS: In pressure overload-induced heart failure mice, 217 mRNAs showed differential expression, with FTO and IGF2BP2 identified as m6A methylation enzymes. Subsequent methylation sequencing revealed 884 highly-methylated and 178 lowly-methylated peaks, establishing a network linking Fto and Igf2bp2 with these peaks. Additionally, miRNA sequencing identified 156 differentially expressed miRNAs, including let-7b-5p and miR-23b-3p, predicted as m6Aregulating miRNAs, both elevated in heart failure patients. CONCLUSION: miR-23b-3p and let-7b-5p are identified as potential regulators of RNA methylation in heart failure, acting via FTO and IGF2BP2, offering new insights into the role of miRNA-mediated RNA methylation and its potential therapeutic avenues for heart failure.

Sono-responsive smart nanoliposomes for precise and rapid hemostasis application.

Massive hemorrhage caused by injuries and surgical procedures is a major challenge in emergency medical scenarios. Conventional means of hemostasis often fail to rapidly and efficiently control bleeding, especially in inaccessible locations. Herein, a type of smart nanoliposome with ultrasonic responsiveness, loaded with thrombin (thrombin@liposome, named TNL) was developed to serve as an efficient and rapid hemostatic agent. Firstly, the hydrophilic cavities of the liposomes were loaded onto the sono-sensitive agent protoporphyrin. Secondly, a singlet oxygen-sensitive chemical bond was connected with the hydrophobic and hydrophilic ends of liposomes in a chemical bond manner. Finally, based on the host guest effect between ultrasound and the sono-sensitizer, singlet oxygen is continuously generated, which breaks the hydrophobic and hydrophilic ends of liposome fragments, causing spatial collapse of the TNL structure, swiftly releases thrombin loaded in the hydrophilic capsule cavity, thereby achieving accurate and rapid local hemostasis (resulted in a reduction of approximately 67% in bleeding in the rat hemorrhage model). More importantly, after thorough assessments of biocompatibility and biodegradability, it has been confirmed that TNL possesses excellent biosafety, providing a new avenue for efficient and precise hemostasis.

Cucurbitacin E Alleviates Colonic Barrier Function Impairment and Inflammation Response and Improves Microbial Composition on Experimental Colitis Models.

Purpose: Cucurbitacins, which are found in a variety of medicinal plants, vegetables and fruits, were known for their diverse pharmacological and biological activities, including anticancer, anti-oxidative and anti-inflammatory effects. Cucurbitacin E, one of the major cucurbitacins, was recently proved to inhibit inflammatory response. Methods: To explore the therapeutic effects of cucurbitacin E on colitis and the underlying mechanisms, male mice drunk water containing 2.5% dextran sulfate sodium (DSS) to establish colitis model and administrated with cucurbitacin E during and after DSS treatment. The disease activity index was scored and colonic histological damage was observed. Intestinal tight junction and inflammatory response were determined. 16S rRNA and transcriptome sequencing were performed to analyze gut microbiota composition and gene expression, respectively. Results: We found that cucurbitacin E alleviated DSS-induced body weight loss and impaired colonic morphology. Cucurbitacin E decreased the expression of inflammatory cytokines and cell apoptosis, and maintained barrier function. Additionally, cucurbitacin E retrieved DSS-induced alterations in the bacterial community composition. Furthermore, a variety of differentially expressed genes (DEGs) caused by cucurbitacin E were enriched in several pathways including the NFκB and TNF signaling pathways as well as in Th17 cell differentiation. There was a close relationship between DEGs and bacteria such as Escherichia-Shigella and Muribaculaceae. Conclusion: Our results revealed that cucurbitacin E may exert protective effects on colitis via modulating inflammatory response, microbiota composition and host gene expression. Our study supports the therapeutic potential of cucurbitacin E in colitis and indicates that gut microbes are potentially therapeutic targets.

Resistance exercise upregulates Irisin expression and suppresses myocardial fibrosis following myocardial infarction via activating AMPK-Sirt1 and inactivating TGFß1-Smad2/3.

AIM: To reveal the contribution of Irisin in the beneficial effects of resistance exercise on myocardial fibrosis (MF) and cardiac function in the mice with myocardial infarction (MI). METHODS: The MI model was built by ligating the left anterior descending coronary artery in Fndc5 knockout mice (Fndc5-/-). Resistance exercise was started one week after surgery and continued for four weeks. In addition, H2O2, AICAR, recombinant human Irisin protein (rhIRISIN), and Sirt1 shRNA lentivirus (LV-Sirt1 shRNA) were used to intervene primary isolated cardiac fibroblasts (CFs). MF was observed through Masson staining, and apoptosis was assessed using TUNEL staining. MDA and T-SOD contents were detected by biochemical kits. The expression of proteins and genes was detected by Western blotting and RT-qPCR. RESULTS: Resistance exercise increased Fndc5 mRNA level, inhibited the activation of TGFß1-TGFßR2-Smad2/3 pathway, activated AMPK-Sirt1 pathway, reduced the levels of oxidative stress, apoptosis, and MF in the infarcted heart, and promoted cardiac function. However, Fndc5 knockout attenuated the protective effects of resistance exercise on the MI heart. Results of the in vitro experiments showed that AICAR and rhIRISIN intervention activated the AMPK-Sirt1 pathway and inactivated the TGFß1-Smad2/3 pathway, and promoted apoptosis in H2O2-treated CFs. Notably, these effects of rhIRISIN intervention, except for the TGFßR2 expression, were attenuated by LV-Sirt1 shRNA. CONCLUSION: Resistance exercise upregulates Fndc5 expression, activates AMPK-Sirt1 pathway, inhibits the activation of TGFß1-Smad2/3 pathway, attenuates MF, and promotes cardiac function after MI.

Fine-Tuning Pyridoxal 5'-Phosphate Synthesis in Escherichia coli for Cadaverine Production in Minimal Culture Media.

Cadaverine is a critical C5 monomer for the production of polyamides. Pyridoxal 5'-phosphate (PLP), as a crucial cofactor for the key enzyme lysine decarboxylase in the cadaverine biosynthesis pathway, has seen a persistent shortage, leading to limitations in cadaverine production. To address this issue, a dual-pathway strategy was implemented, synergistically enhancing both endogenous and heterologous PLP synthesis modules and resulting in improved PLP synthesis. Subsequently, a growth-stage-dependent molecular switch was introduced to balance the precursor competition between PLP synthesis and cell growth. Additionally, a PLP sensor-based negative feedback circuit was constructed by integrating a newly identified PLP-responsive promoter PygjH and an arabinose-regulated system, dynamically regulating the expression of the PLP synthetic genes and preventing excessive intracellular PLP accumulation. The optimal strain, L18, cultivated in the minimal medium AM1, demonstrated cadaverine production with a titer, yield, and productivity of 64.03 g/L, 0.23 g/g glucose, and 1.33 g/L/h, respectively. This represents the highest titer reported to date in engineered Escherichia coli by fed-batch fermentation in a minimal medium.

Bilateral efforts to improve SERS detection efficiency of exosomes by Au/Na7PMo11O39 Combined with Phospholipid Epitope Imprinting.

Detection of cancer-related exosomes in body fluids has become a revolutionary strategy for early cancer diagnosis and prognosis prediction. We have developed a two-step targeting detection method, termed PS-MIPs-NELISA SERS, for rapid and highly sensitive exosomes detection. In the first step, a phospholipid polar site imprinting strategy was employed using magnetic PS-MIPs (phospholipids-molecularly imprinted polymers) to selectively isolate and enrich all exosomes from urine samples. In the second step, a nanozyme-linked immunosorbent assay (NELISA) technique was utilized. We constructed Au/Na7PMo11O39 nanoparticles (NPs) with both surface-enhanced Raman scattering (SERS) property and peroxidase catalytic activity, followed by the immobilization of CD9 antibodies on the surface of Au/Na7PMo11O39 NPs. The Au/Na7PMo11O39-CD9 antibody complexes were then used to recognize CD9 proteins on the surface of exosomes enriched by magnetic PS-MIPs. Lastly, the high sensitivity detection of exosomes was achieved indirectly via the SERS activity and peroxidase-like activity of Au/Na7PMo11O39 NPs. The quantity of exosomes in urine samples from pancreatic cancer patients obtained by the PS-MIPs-NELISA SERS technique showed a linear relationship with the SERS intensity in the range of 6.21 × 107-2.81 × 108 particles/mL, with a limit of detection (LOD) of 5.82 × 107 particles/mL. The SERS signal intensity of exosomes in urine samples from pancreatic cancer patients was higher than that of healthy volunteers. This bidirectional MIPs-NELISA-SERS approach enables noninvasive, highly sensitive, and rapid detection of cancer, facilitating the monitoring of disease progression during treatment and opening up a new avenue for rapid early cancer screening.

Stable Photo-Rechargeable Al Battery for Enhancing Energy Utilization.

Photovoltaic cells (PVs) are able to convert solar energy to electric energy, while energy storage devices are required to be equipped due to the fluctuations of sunlight. However, the electrical connection of PVs and energy storage devices leads to increased energy consumption, and thus energy storage ability and utilization efficiency are decreased. One of the solutions is to explore an integrated photoelectrochemical energy conversion-storage device. Up to date, the integrated photo-rechargeable Li-ion batteries often suffer from unstable photo-active materials and flammable electrolytes under illumination, with concerns in safety risks and limited lifetime. To address the critical issues, here a novel photo-rechargeable aluminum battery (PRAB) is designed with safe ionic liquid electrolytes and stable polyaniline photo-electrodes. The integrated PRAB presents stable operation with an enhanced reversible specific capacity ≈191% under illumination. Meanwhile, a simplified continuum model is established to provide rational guidance for designing electrode structures along with a charging/discharging strategy to meet the practical operation conditions. The as-designed PRAB presents an energy-saving efficiency ≈61.92% upon charging and an energy output increment ≈31.25% during discharging under illumination. The strategy of designing and fabricating stable and safe photo-rechargeable non-aqueous Al batteries highlights the pathway for substantially promoting the utilization efficiency of solar energy.

Evaluation of adverse reactions induced by anti-tuberculosis drugs among hospitalized patients in Wuhan, China: A retrospective study.

The study aims to estimate the incidence and risk factors of adverse drug reactions (ADRs) induced by anti-tuberculosis (TB) drugs. A single center retrospective analysis of patients taking anti-TB therapy from January 2016 to December 2018 in the hospital was conducted. Univariate and multivariate logistic regression analysis were used to identify these risk factors of ADRs induced by anti-TB drugs. Among 1430 patients receiving anti-TB therapy, 440 (30.77%) patients showed at least 1 ADR induced by anti-TB drugs. Hyperuricemia was the most common ADR, followed by hepatic function test abnormality, liver damage and gastrointestinal reactions. Significant differences (P < .05) were also seen in diabetes, age, treatment duration, type of TB (extrapulmonary) and some therapeutic regimens between ADR group and non-ADR group, respectively. Multivariate logistic regression analysis showed that treatment duration (OR = 1.029, 95%CI[1.018-1.040], P = .000), type of TB (extrapulmonary, OR = 1.487, 95%CI[1.134-1.952], P = .004) and some therapeutic regimens (HREZ, OR = 1.425, 95%CI[0.922-2.903], P = .001; HRZS, OR = 2.063, 95% CI[1.234-3.449], P = .006; HRZ, OR = 3.623, 95%CI[2.289-5.736], P = .000) were risk factors for ADRs induced by anti-TB drugs. Anti-TB drugs usually induced the occurrence of severe and frequent adverse effects, such as hyperuricemia. Treatment duration, HREZ, HRZS and HRZ regimens, and type of TB (extrapulmonary) should be considered as high-risk factors. Thus, it should be recommended to consider optimum management during anti-TB therapy, particularly hyperuricemia monitoring and hepatic function test.

Rational Design of the Spatial Effect in a Fe(II)/α-Ketoglutarate-Dependent Dioxygenase Reverses the Regioselectivity of C(sp3)-H Bond Hydroxylation in Aliphatic Amino Acids.

The hydroxylation of remote C(sp3)-H bonds in aliphatic amino acids yields crucial precursors for the synthesis of high-value compounds. However, accurate regulation of the regioselectivity of remote C(sp3)-H bonds hydroxylation in aliphatic amino acids continues to be a common challenge in chemosynthesis and biosynthesis. In this study, the Fe(II)/α-ketoglutarate-dependent dioxygenase from Bacillus subtilis (BlAH) was mined and found to catalyze hydroxylation at the γ and δ sites of aliphatic amino acids. Through crystal structure analysis, molecular dynamic simulation and quantum chemical calculations revealed that regioselectivity was regulated by the spatial effect of BlAH. Based on this result, the spatial effect of BlAH was reconstructed to stabilize the transition state at the δ site of aliphatic amino acids, thereby successfully reversing the γ site regioselectivity to the δ site. For example, the regioselectivity of L-Homoleucine (5a) was reversed from the γ site (1:12) to the δ site (>99:1). The present study not only expands the toolbox of biocatalysts for the regioselective functionalization of remote C(sp3)-H bonds, but also provides a theoretical guidance for the precision-driven modification of similarly remote C(sp3)-H bonds in complex molecules.

Link Brain-Wide Projectome to Neuronal Dynamics in the Mouse Brain.

Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.

[Research progress on mechanisms of ligustilide in treatment of nervous system diseases].

Ligustilide is the main active component of the volatile oil from Angelica sinensis and Ligusticum chuanxiong in the Umbelliferae family. It is a phthalein compound with anti-inflammatory, analgesic, antioxidant, anti-tumor, anti-atherosclerosis, neuroprotective, and other pharmacological effects. It can improve the permeability of the blood-brain barrier and has important potential in the treatment of neurodegenerative diseases and other nervous system diseases, such as Alzheimer's disease, ischemic stroke, Parkinson's disease, vascular dementia, and depression. Therefore, the mechanism of ligustilide in the treatment of nervous system diseases was summarized to provide a reference for drug development and clinical application.