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Abstract Objective To compare the surgical trauma and outcomes between oblique lateral interbody fusion (OLIF) and posterior fixation and posterior lumbar interbody fusion (PLIF) with fixation for adult degenerative scoliosis (ADS). Methods We included ADS patients who underwent OLIF with fixation or PLIF with fixation treatment from June 2020 to December 2022. The preoperative and postoperative spinal pelvic parameters were measured using X-rays. Clinical symptoms were measured using the Oswestry Disability Index and a visual analog scale. We recorded operation time, intraoperative blood loss, blood transfusion, albumin infusion, surgical fixation segment, surgical osteotomy segment, time, and drainage volume. Results Forty patients with ADS were included: 20 with OLIF with posterior fixation and 20 with PLIF matched for age, sex, pelvic incidence, and Cobb angle with the OLIF group. There were no significant differences in age, gender, BMI, preoperative spinal parameters, or preoperative clinical symptoms between the groups (p > 0.05). There were no statistical differences in postoperative spinal parameters or clinical symptoms (p > 0.05). Patients in the OLIF group had less intraoperative blood loss (p

ObjectivesIn order to assess the vitality of shipborne equipment consists of important components of a warship system under the action of an anti-ship missile implosion load, this paper propose a response failure analysis method.MethodsThe shock response of a typical hull structure subjected to an internal explosion is numerically simulated, and the shock response spectrum is calculated to determine the impact environment of the location of the shipborne equipment. ResultsThrough the shock response spectrum of the typical position, the shock response parameters of shipborne equipment in different positions and at different installation frequencies are obtained, and a failure probability model is established through comparison with the shock design value, thereby forming a shock response failure analysis method for shipborne equipment. ConclusionsThe method proposed in this paper allows the calculation of the failure probability of typical shipborne equipment, and the results can provide references for the damage assessment and failure analysis of shipborne equipment under implosion load.

Abstract Properly integrating spatially resolved transcriptomics (SRT) generated from different batches into a unified gene-spatial coordinate system could enable the construction of a comprehensive spatial transcriptome atlas. Here, we propose SPIRAL, consisting of two consecutive modules: SPIRAL-integration, with graph domain adaptation-based data integration, and SPIRAL-alignment, with cluster-aware optimal transport-based coordination alignment. We verify SPIRAL with both synthetic and real SRT datasets. By encoding spatial correlations to gene expressions, SPIRAL-integration surpasses state-of-the-art methods in both batch effect removal and joint spatial domain identification. By aligning spots cluster-wise, SPIRAL-alignment achieves more accurate coordinate alignments than existing methods.

Although oily wastewater treatment realized by superwetting materials has attracted heightened attention in recent years, how to treat enormous-volume emulsion wastewater is still a tough problem, which is ascribed to the emulsion accumulation. Herein, to address this problem, a material is presented by subtly integrating chemical demulsification and 3D inner-outer asymmetric wettability to a sponge substrate, and thus wettability gradient-driven oil directional transport for achieving unprecedented enormous-volume emulsion wastewater treatment is realized based on a “demulsification-transport” mechanism. The maximum treatment volume realized by the sponge is as large as 3 L (2.08 × 104 L per cubic meter of the sponge) in one cycle, which is about 100 times of the reported materials. Besides, owing to the large pore size of the sponge, 9000 L m2 h−1 (LMH) separation flux and 99.5% separation efficiency are realized simultaneously, which overcomes the trade-off dilemma. Such a 3D inner-outer asymmetric sponge displaying unprecedented advantage in the treatment volume can promote the development of the oily wastewater treatment field, as well as expand the application prospects of superwetting materials, especially in continuous water treatment.

Abstract Cell lines are valuable resources as model for human biology and translational medicine. It is thus important to explore the concordance between the expression in various cell lines vis-à-vis human native and disease tissues. In this study, we investigate the expression of all human protein-coding genes in more than 1,000 human cell lines representing 27 cancer types by a genome-wide transcriptomics analysis. The cell line gene expression is compared with the corresponding profiles in various tissues, organs, single-cell types and cancers. Here, we present the expression for each cell line and give guidance for the most appropriate cell line for a given experimental study. In addition, we explore the cancer-related pathway and cytokine activity of the cell lines to aid human biology studies and drug development projects. All data are presented in an open access cell line section of the Human Protein Atlas to facilitate the exploration of all human protein-coding genes across these cell lines.

Image guided photodynamic therapy (PDT) combines fluorescence tracing and phototherapy, which can achieve a more accurate and effective treatment effect. However, traditional photosensitizers are limited by the aggregation-caused fluorescence quenching (ACQ) effect and low reactive oxygen species (ROS) generation in a hypoxic environment, resulting in poor imaging and treatment effect. Herein, we report a tricyano-methylene-pyridine (TCM)-based Type I aggregation-induced emission (AIE) photosensitizer (TCM-MBP), the strong electron acceptance (D-A) effect extends the wavelength to near-infrared (NIR) region to reduce the autofluorescence interference, and oxygen atoms provide lone pair electrons to enhance the inter system crossing (ISC) rate, thereby promoting the generation of more triplet states to produce ROS. The AIE photosensitizer TCM-MBP exhibited low oxygen dependence, NIR emission, and higher ROS production compared to commercially available Ce 6 and RB. After encapsulation with DSPE-PEG2000, TCM-MBP nanoparticles (TCM-MBP NPs) could penetrate to visualize cells and efficiently kill cancer cells upon light irradiation. This study provides an oxygen-independent AIE photosensitizer, which has great potential to replace the commercial ACQ photosensitizers.

A superior cultivar of dried jujube in China is ‘Huizao’ (HZ) jujube. Nonetheless, detailed evaluations of the texture quality of HZ fruit have been the subject of few studies. Texture is a significant indicator of the sensory and processed quality of a fruit. Here, we differentiate and characterize the texture quality of HZ fruit from the four primary producing regions in southern Xinjiang, as well as develop a system for assessing the texture quality of HZ fruit. Correlation investigation indicated strong relationships between the springiness, chewiness, cohesiveness, gumminess, and hardness of HZ fruit. Furthermore, according to the factor molecules, the texture quality of HZ fruit in the four production areas was evaluated as Bazhou (1.24) > Hotan (0.773) > Kashi (−0.577) > Aksu (−0.852). RDA analysis of six texture quality parameters and 24 climate conditions identified higher mean temperature (TEM) and lower relative humidity (RHU) as the primary factors contributing to the improved texture quality of HZ fruit in Xinjiang. This study identified the variations in the texture of HZ fruit in the four primary producing regions of Southern Xinjiang. The HZ fruit in Hotan and Bazhou exhibit superior springiness and stickiness, while the fruit in Aksu and Kashi exhibit greater hardness. The texture of HZ fruit is significantly influenced by springiness, hardness, and adhesiveness, and a comprehensive evaluation model has been established through this research. This will provide a theoretical foundation for optimizing the dominant producing areas and regional production of HZ varieties in Xinjiang.

In this paper, the influence of bismuth content and heating rate on the morphology of MnS inclusions in bismuth-containing free-cutting steel during heating was investigated through in situ observation experiments and 3D electrolytic corrosion experiments. By observing the microscopic morphology of inclusions in the original sample, it was found that MnS inclusions in the sample were rod-shaped, spherical, irregular, small in size, and mostly clustered at the grain boundary in the form of chains and divergences. With the addition of bismuth, MnS inclusions of a larger size appear in the steel, and the inclusions distributed at grain boundaries are also reduced. When bismuth (0.010~0.020%) is added to the steel, MnS is mainly spherical and uniformly dispersed in the steel matrix. If the bismuth content is too high, the inclusions aggregate. Through in situ observations of the inclusions in the sample, it was found that the addition of bismuth in the heating process delays the appearance of ferrite grain boundaries and contributes to the spheroidization of MnS inclusions. Mn and S elements can fully diffuse slowly in the matrix with a heating rate below 1 °C/s and a long holding time (300 s), which provides the possibility for the spheroidization of MnS inclusions.

Muscles play an indispensable role in human life. Surface electromyography (sEMG), as a non-invasive method, is crucial for monitoring muscle status. It is characterized by its real-time, portable nature and is extensively utilized in sports and rehabilitation sciences. This study proposed a wireless acquisition system based on multi-channel sEMG for objective monitoring of grip force. The system consists of an sEMG acquisition module containing four-channel discrete terminals and a host computer receiver module, using Bluetooth wireless transmission. The system is portable, wearable, low-cost, and easy to operate. Leveraging the system, an experiment for grip force prediction was designed, employing the bald eagle search (BES) algorithm to enhance the Random Forest (RF) algorithm. This approach established a grip force prediction model based on dual-channel sEMG signals. As tested, the performance of acquisition terminal proceeded as follows: the gain was up to 1125 times, and the common mode rejection ratio (CMRR) remained high in the sEMG signal band range (96.94 dB (100 Hz), 84.12 dB (500 Hz)), while the performance of the grip force prediction algorithm had an R2 of 0.9215, an MAE of 1.0637, and an MSE of 1.7479. The proposed system demonstrates excellent performance in real-time signal acquisition and grip force prediction, proving to be an effective muscle status monitoring tool for rehabilitation, training, disease condition surveillance and scientific fitness applications.

Abstract Glioblastoma is the most common type of brain tumor. Due to the presence of the blood-brain barrier, the effects of chemotherapy have been unsatisfactory. The combination of focused ultrasound and microbubbles to reversibly open the blood-brain barrier is now considered a key factor in improving treatment outcomes of glioblastoma. In this study, we developed bionic drug delivery microbubbles, which in combination with focused ultrasound had an obvious inhibitory effect on glioblastoma. We extracted the brain microvascular cell membranes, combined them with lipid components, and loaded them with superparamagnetic iron oxide and doxorubicin to prepare biomimetic drug delivery microbubbles (FeDOX@cellMBs). We demonstrated that FeDOX@cellMBs retained the intrinsic properties of loading, such as magnetic properties and drug toxicity, both in vitro and in vivo. FeDOX@cellMBs exhibited good tumor targeting and uptake under the combined action of magnetic and focused ultrasound. Importantly, the FeDOX@cellMBs demonstrated excellent internal stability and effectively inhibited tumor growth in orthotopic glioblastoma mice. Finally, organ H&E staining confirmed that FeDOX@cellMBs were safe for use. In conclusion, FeDOX@cellMBs successfully penetrated the blood-brain barrier and effectively inhibited glioblastoma growth under the combined effects of focused ultrasound and magnetic stimulation. These results provide a new approach for the treatment of glioblastoma, with implications for future clinical translation.

Abstract Understanding the evolutionary forces in speciation is a central goal in evolutionary biology. Asian cultivated rice has two subspecies, indica and japonica, but the underlying mechanism of the partial reproductive isolation between them remains obscure. Here we show a presence-absence variation (PAV) at the Se locus functions as an indica-japonica reproductive barrier by causing hybrid sterility (HS) in indica-japonica crosses. The locus comprises two adjacent genes: ORF3 encodes a sporophytic pollen killer, whereas ORF4 protects pollen in a gametophytic manner. In F1 of indica-japonica crosses, pollen with the japonica haplotype, which lacks the sequence containing the protective ORF4, is aborted due to the pollen-killing effect of ORF3 from indica. Evolutionary analysis suggests ORF3 is a gene associated with the Asian cultivated rice species complex, and the PAV has contributed to the reproductive isolation between the two subspecies of Asian cultivated rice. Our analyses provide perspectives on rice inter-subspecies post-zygotic isolation, and will promote efforts to overcome reproductive barriers in indica-japonica hybrid rice breeding.

Abstract Objectives General anesthesia results in a state of unconsciousness that is similar to sleep. In recent years, increasing evidence has reported that astrocytes play a crucial role in regulating sleep. However, whether astrocytes are involved in general anesthesia is unknown. Methods In the present study, the designer receptors exclusively activated by designer drugs (DREADDs) approach was utilized to specifically activate astrocytes in the basal forebrain (BF) and observed its effect on isoflurane anesthesia. One the other side, L-α-aminoadipic acid was used to selectively inhibit astrocytes in the BF and investigated its influence on isoflurane-induced hypnotic effect. During the anesthesia experiment, cortical electroencephalography (EEG) signals were recorded as well. Results The chemogenetic activation group had a significantly shorter isoflurane induction time, longer recovery time, and higher delta power of EEG during anesthesia maintenance and recovery periods than the control group. Inhibition of astrocytes in the BF delayed isoflurane-induced loss of consciousness, promoted recovery, decreased delta power and increased beta and gamma power during maintenance and recovery periods. Conclusions The present study suggests that astrocytes in the BF region are involved in isoflurane anesthesia and may be a potential target for regulating the consciousness state of anesthesia.

The incidence rate of depression, a mental disorder, is steadily increasing and has the potential to become a major global disability factor. Given the complex pathological mechanisms involved in depression, the use of conventional antidepressants may lead to severe complications due to their side effects. Hence, there is a critical need to explore the development of novel antidepressants. Ferroptosis, a newly recognized form of cell death, has been found to be closely linked to the onset of depression. Several studies have indicated that certain active ingredients can ameliorate depression by modulating the ferroptosis signaling pathway. Notably, traditional Chinese medicine (TCM) active ingredients and TCM prescriptions have demonstrated promising antidepressant effects in previous investigations owing to their unique advantages in antidepressant therapy. Building upon these findings, our objective was to review recent relevant research and provide new insights and directions for the development and application of innovative antidepressant strategies.

BackgroundDelirium is a common complication among intensive care unit (ICU) patients that is linked to negative clinical outcomes. However, adherence to the Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU (PADIS guidelines), which recommend the use of the ABCDEF bundle, is sub-optimal in routine clinical care. To address this issue, AI-AntiDelirium, a nurse-led artificial intelligence-assisted prevention and management tool for delirium, was developed by our research team. Our pilot study yielded positive findings regarding the use of AI-AntiDelirium in preventing patient ICU delirium and improving activities of daily living and increasing intervention adherence by health care staff.MethodsThe proposed large-scale pragmatic, open-label, parallel-group, cluster randomized controlled study will assess the impact of AI-AntiDelirium on the incidence of ICU delirium and delirium-related outcomes. Six ICUs in two tertiary hospitals in China will be randomized in a 1:1 ratio to an AI-AntiDelirium or a PADIS guidelines group. A target sample size of 1,452 ICU patients aged 50 years and older treated in the ICU for at least 24 hours will be included. The primary outcome evaluated will be the incidence of ICU delirium and the secondary outcomes will be the duration of ICU delirium, length of ICU and hospital stay, ICU and in-hospital mortality rates, patient cognitive function, patient activities of daily living, and ICU nurse adherence to the ABCDEF bundle.DiscussionIf this large-scale trial provides evidence of the effectiveness of AI-AntiDelirium, an artificial intelligence-assisted system tool, in decreasing the incidence of ICU delirium, length of ICU and hospital stay, ICU and in-hospital mortality rates, patient cognitive function, and patient activities of daily living while increasing ICU nurse adherence to the ABCDEF bundle, it will have a profound impact on the management of ICU delirium in both research and clinical practice.Clinical trial registrationChiCTR1900023711 (Chinese Clinical Trial Registry).

BackgroundThe diagnosis of lung adenocarcinoma (LUAD) leptomeningeal metastasis (LM) remains a clinical challenge. Human epididymis protein 4 (HE4) functions as a novel tumor biomarker for cancers. This study aimed to assess the diagnostic value of cerebrospinal fluid (CSF) HE4, and combined with CEACAM6, for LUAD LM.MethodsThe CSF HE4 protein level was measured in two independent cohorts by electrochemiluminescence. Test cohort included 58 LUAD LM patients, 22 LUAD patients without LM (Wiot-LM), and 68 normal controls. Validation cohort enrolled 50 LUAD LM patients and 40 normal controls, in parallel with Wiot-LM patients without brain metastases (19 Wiot-LM/BrM patients) or with BrM (26 BrM patients). The CSF level of CEA, CA125, CA153, CA199, CA724, NSE and ProGRP of these samples was measured by electrochemiluminescence, whereas the CSF CEACAM6 level was detected by enzyme-linked immunosorbent assay (ELISA). In addition, the serum level of these biomarkers was detected by same method as CSF.ResultsThe level of HE4 or CEACAM6 in CSF samples from LUAD LM patients was significantly higher than those from normal controls and Wiot-LM patients. The HE4 or CEACAM6 level in CSF was higher than that in serum of LM patient. The CSF HE4 or CEACAM6 level for distinguished LM from Wiot-LM showed good performance by receiver-operating characteristic analysis. The better discriminative power for LM was achieved when HE4 was combined with CEACAM6. In addition, the CSF HE4 and CEACAM6 level showed little or no difference between Wiot-LM/BrM and BrM patients, the BrM would not significantly influence the HE4 or CEACAM6 level in CSF. The diagnostic power of CSF CA125, CA153, CA199, CA724, NSE and ProGRP for LUAD LM were not ideal.ConclusionThe combination with HE4 and CEACAM6 has the promising application for the diagnosis of LUAD LM.

ObjectivesPrevious studies have confirmed a link between specific inflammatory cytokines and inflammatory bowel disease (IBD), but the causal relationship between them is not completely clear. This Mendelian Randomization (MR) study aims to evaluate the causal relationship between 18 inflammatory cytokines and inflammatory bowel disease.MethodTwo-sample Mendelian randomization utilized genetic variances associated with IBD from two extensive publicly available genome-wide association studies (GWAS) (Crohn’s Disease (CD): 12,194 cases and 28,072 controls; Ulcerative Colitis (UC): 12,336 cases and 33,609 controls). The data of inflammatory cytokines was acquired from a GWAS including 8,293 healthy participants. We used inverse variance weighted method, MR-Egger, weighted median, simple model and weighted model to evaluate the causal relationship between inflammatory cytokines and IBD. Sensitivity analysis includes heterogeneity and pleiotropy analysis to evaluate the robustness of the results.ResultsThe findings indicated suggestive positive associations between Interleukin-13 (IL-13) and macrophage migration inhibitory factor (MIF) with CD (odds ratio, OR: 1.101, 95%CI: 1.021-1.188, p = 0.013; OR: 1.134, 95%CI: 1.024-1.255, p = 0.015). IL-13 also displayed a significant positive correlation with UC (OR: 1.099, 95%CI: 1.018-1.186, p = 0.016). Stem cell factor (SCF) was suggested to be associated with the development of both CD and UC (OR: 1.032, 95%CI: 0.973-1.058, p = 0.012; OR: 1.038, 95%CI: 1.005-1.072, p = 0.024).ConclusionThis study proposes that IL-13 may be a factor correlated with the etiology of IBD (CD and UC), while MIF just be specifically associated with CD. Additionally, SCF appears more likely to be involved in the downstream development of IBD (CD and UC).

Immune-checkpoint blockade (ICB) therapies have been widely used in clinical treatment of cancer patients, but only 20–30% of patients benefit from immunotherapy. Therefore, it is important to decipher the molecular mechanism of resistance to ICB and develop new combined treatment strategies. PD-L1 up-regulation in tumor cells contributes to the occurrence of immune escape. Increasing evidence shows that its transcription level is affected by multiple factors, which limits the objective response rate of ICB. Fibroblast growth factor 19 (FGF19), a member of the fibroblast growth factor family, is widely involved in the malignant progression of many tumors by binding to fibroblast growth factor receptor 4 (FGFR4). In this study, we confirmed that FGF19 acts as a driver gene in hepatocellular carcinoma (HCC) progression by binding to FGFR4. The up-regulation of FGF19 and FGFR4 in HCC is associated with poor prognosis. We found that FGF19/FGFR4 promoted the proliferation and invasion of HCC cells by driving IGF2BP1 to promote PD-L1 expression. Knockdown of FGFR4 significantly reduced the expression of IGF2BP1/PD-L1 and inhibited the proliferation and invasion of HCC cells. These biological effects are achieved by inhibiting the PI3K/AKT pathway. The combination of FGFR4 knockdown and anti-PD-1 antibody greatly suppressed tumor growth and enhanced the sensitivity of immunotherapy, highlighting the clinical significance of FGF19/FGFR4 activation in immunotherapy.

ObjectiveEvidence from previous studies indicates that impulsive behaviors are closely linked to alcohol use and misuse and that female drinkers are more impulsive than male drinkers. However, studies investigating the psychological mechanisms of alcohol use and impulsivity based on sex differences are relatively limited.MethodsThis cross-sectional study comprised 713 residents from 16 cities in Anhui Province, China. Each subject was evaluated for self-reporting measures using several questionnaires, including the general information questionnaire, the Alcohol Use Disorders Identification Test (AUDIT), the Prospective and Retrospective Memory Questionnaire (PRM), the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), and the Barratt Impulsiveness Scale-11 (BIS-11).ResultsExecutive function and prospective memory may serve as intermediary links between alcohol use and impulsivity. Although the female alcohol usage level was significantly lower than that of males, the female drinkers had more severe executive dysfunction, prospective memory impairment, and impulsivity than male drinkers. Sex moderated the relationship between alcohol use and impulsivity. Furthermore, the indirect effect of executive function, and prospective memory between AUDIT and BIS was more significant in males than in females.ConclusionAlcohol consumption may be associated with impulsivity formation through executive dysfunction and PM impairment, implying that impulsivity in those with AUD or at risk for AUD might be treated by improving EF and PM. Alcohol use may cause more severe executive dysfunction, PM impairment, and impulsive behavior in females than in males, and impulsive behavior in women with AUD was more likely to be due to the direct effects of alcohol consumption, while impulsive behavior in men with AUD was more likely to be due to the indirect effects of executive dysfunction and PM impairment. These findings provide both clinical and theoretical foundations for addressing issues related to alcohol use.

BackgroundDespite advancements in hepatocellular carcinoma (HCC) treatments, the prognosis for patients remains suboptimal. Cumulative evidence suggests that programmed cell death (PCD) exerts crucial functions in HCC. PCD-related genes are potential predictors for prognosis and therapeutic responses.MethodsA systematic analysis of 14 PCD modes was conducted to determine the correlation between PCD and HCC. A novel machine learning-based integrative framework was utilized to construct the PCD Index (PCDI) for prognosis and therapeutic response prediction. A comprehensive analysis of PCDI genes was performed, leveraging data including single-cell sequencing and proteomics. GBA was selected, and its functions were investigated in HCC cell lines by in vitro experiments.ResultsTwo PCD clusters with different clinical and biological characteristics were identified in HCC. With the computational framework, the PCDI was constructed, demonstrating superior prognostic predictive efficacy and surpassing previously published prognostic models. An efficient clinical nomogram based on PCDI and clinicopathological factors was then developed. PCDI was intimately associated with immunological attributes, and PCDI could efficaciously predict immunotherapy response. Additionally, the PCDI could predict the chemotherapy sensitivity of HCC patients. A multilevel panorama of PCDI genes confirmed its stability and credibility. Finally, the knockdown of GBA could suppress both the proliferative and invasive capacities of HCC cells.ConclusionThis study systematically elucidated the association between PCD and HCC. A robust PCDI was constructed for prognosis and therapy response prediction, which would facilitate clinical management and personalized therapy for HCC.

Objective: To systematically evaluate the efficacy and safety of the Chinese medicine detoxification and dredging collaterals in treating carotid atherosclerosis (CAS).Methods: A systematic and comprehensive search of nine relevant domestic and international databases were conducted from their inception until June 2022. The methodological quality of the included trials was evaluated, and the efficacy and safety were comprehensively analyzed. After applying the inclusion and exclusion criteria to the randomized controlled trials (RCTs), the research quality evaluation and data extraction were conducted, followed by a meta-analysis of the selected articles. The Cochrane’s Bias risk assessment was utilized to evaluate the quality of the evidence.Results: Of the 2,660 studies initially retrieved, 14 studies were included, involving a total of 1,518 patients. The results of the meta-analysis indicated that the clinical efficacy of the Detoxification and Collateral Dredging method in the treatment of CAS was superior to that of western medicine treatment alone, and the difference was statistically significant [RR = 1.23, 95% CI (1.13, 1.34)] Furthermore, carotid intima-media thickness [Mean Difference (MD) = −0.10, 95% CI (−0.13, −0.08)] and Crouse plaque score [MD = −0.54, 95% CI (−0.75, −0.32)] were significantly lower in the Detoxification and Collateral Dredging group compared to the pure western medicine treatment group. The difference was statistically significant. In addition, serum total cholesterol [MD = −0.70, 95% CI (−0.85, −0.55)] and low-density lipoprotein cholesterol [MD = −0.70, 95% CI (−0.85, −0.55)] were lower in the Detoxification and Collateral Dredging group than in the Western medicine group, with all differences being statistically significant. Serum high-density lipoprotein cholesterol was higher in the Detoxification and Collateral Dredging group compared to the pure western medicine group, and the difference was statistically significant [MD = 0.17, 95% CI (0.11, 0.23)].Conclusion: The use of Chinese medicine Detoxification and Collateral Dredging approach in the treatment of CAS may offer benefits in improving carotid atherosclerotic plaque and reducing blood lipid levels, with a safety profile superior to that of western medicine treatment alone.

Abstract Objective To identify factors associated with T1 slope (T1S). Methods A total of 215 patients over 18 years old who underwent whole-spine X-rays to evaluate lower back pain were enrolled in this study. T1S, pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), thoracic kyphosis (TK), lumbar lordosis (LL), cervical lordosis (CL), thoracolumbar kyphosis (TLK), and sagittal vertical axis (SVA) were measured. Patients were divided into balance, compensatory balance, thoracic compensation, and thoracic decompensation groups. Results TK (p

Abstract Background Despite numerous clinical trials and decades of endeavour, there is still no effective cure for Alzheimer's disease. Computational drug repositioning approaches may be employed for the development of new treatment strategies for Alzheimer’s patients since an extensive amount of omics data has been generated during pre-clinical and clinical studies. However, targeting the most critical pathophysiological mechanisms and determining drugs with proper pharmacodynamics and good efficacy are equally crucial in drug repurposing and often imbalanced in Alzheimer’s studies. Methods Here, we investigated central co-expressed genes upregulated in Alzheimer’s disease to determine a proper therapeutic target. We backed our reasoning by checking the target gene’s estimated non-essentiality for survival in multiple human tissues. We screened transcriptome profiles of various human cell lines perturbed by drug induction (for 6798 compounds) and gene knockout using data available in the Connectivity Map database. Then, we applied a profile-based drug repositioning approach to discover drugs targeting the target gene based on the correlations between these transcriptome profiles. We evaluated the bioavailability, functional enrichment profiles and drug-protein interactions of these repurposed agents and evidenced their cellular viability and efficacy in glial cell culture by experimental assays and Western blotting. Finally, we evaluated their pharmacokinetics to anticipate to which degree their efficacy can be improved. Results We identified glutaminase as a promising drug target. Glutaminase overexpression may fuel the glutamate excitotoxicity in neurons, leading to mitochondrial dysfunction and other neurodegeneration hallmark processes. The computational drug repurposing revealed eight drugs: mitoxantrone, bortezomib, parbendazole, crizotinib, withaferin-a, SA-25547 and two unstudied compounds. We demonstrated that the proposed drugs could effectively suppress glutaminase and reduce glutamate production in the diseased brain through multiple neurodegeneration-associated mechanisms, including cytoskeleton and proteostasis. We also estimated the human blood–brain barrier permeability of parbendazole and SA-25547 using the SwissADME tool. Conclusions This study method effectively identified an Alzheimer’s disease marker and compounds targeting the marker and interconnected biological processes by use of multiple computational approaches. Our results highlight the importance of synaptic glutamate signalling in Alzheimer’s disease progression. We suggest repurposable drugs (like parbendazole) with well-evidenced activities that we linked to glutamate synthesis hereby and novel molecules (SA-25547) with estimated mechanisms for the treatment of Alzheimer’s patients.

Abstract Although the clinical application and transformation of exosomes are still in the exploration stage, the prospects are promising and have a profound impact on the future transformation medicine of exosomes. However, due to the limitation of production and poor targeting ability of exosomes, the extensive and rich biological functions of exosomes are restricted, and the potential of clinical transformation is limited. The current research is committed to solving the above problems and expanding the clinical application value, but it lacks an extensive, multi-angle, and comprehensive systematic summary and prospect. Therefore, we reviewed the current optimization strategies of exosomes in medical applications, including the exogenous treatment of parent cells and the improvement of extraction methods, and compared their advantages and disadvantages. Subsequently, the targeting ability was improved by carrying drugs and engineering the structure of exosomes to solve the problem of poor targeting ability in clinical transformation. In addition, we discussed other problems that may exist in the application of exosomes. Although the clinical application and transformation of exosomes are still in the exploratory stage, the prospects are promising and have a profound impact on drug delivery, clinical diagnosis and treatment, and regenerative medicine.

Accurate analysis of the main chemical components of oil-bearing sludge is an important prerequisite for effective soil remediation and resource reuse. However, precise analysis of the extract components is difficult to achieve because of the mutual interference of saturates, aromatics, and resins, collectively called SAR, and asphaltene that are introduced during chloroform extraction. In this study, SAR was efficiently extracted using n-heptane, while asphaltene components were retained in soil because of their insolubility in n-heptane. The maximum yield of SAR extraction was 27.0%, indicating an increase of 1.75% compared to chloroform extraction. The extracted SAR components were separated by chromatography and the main structural units and components were analyzed. The results show that saturates, aromatics, and resins have a single component, a high content of major components, and contain fewer impurities using n-heptane extraction. Moreover, the solubility of asphaltene was inhibited during the effective extraction of SAR components with n-heptane and did not influence the subsequent analysis of SAR component. Efficient SAR extraction, accurate SAR component analysis, and high efficiency asphaltene separation was achieved using n-heptane-extraction-assisted pyrolysis. This provides a new method for the component analysis of oily sludge and promotes its efficient separation.

Abstract Purpose Cervical laminoplasty (CLP) is a developed surgical procedure for the treatment of cervical spondylotic myelopathy (CSM), but only a few of those studies focus on preoperative dynamic cervical sagittal alignment and the study of different degrees of loss of cervical lordosis (LCL) is lacking. This study aimed to analyze patients who underwent CLP to investigate the effect of cervical extension and flexion function on different degrees of LCL. Methods In this retrospective case–control study, we analyzed 79 patients who underwent CLP for CSM between January 2019 and December 2020. We measured the cervical sagittal alignment parameters on lateral radiographs (neutral, flexion, and extension positions) and used Japanese Orthopedic Association (JOA) score to assess clinical outcomes. We defined the extension ratio (EXR) as 100 × Ext ROM (cervical range of extension)/ROM (cervical range of motion). We observed the relationships between collected variables (demographic and radiological variables) and LCL. Patients were classified into the following three groups according to the LCL: stability group: (LCL ≤ 5°); mild loss group (5° 10°). We compared the differences of collected variables (demographic, surgical and radiological variables) among the three groups. Results Seventy-nine patients were enrolled (mean age 62.92 years; 51 men, 28 women) in the study. Among the three groups, cervical Ext ROM was the best in the stability group (p 10° (area under the curve = 0.808, p

Abstract In this paper, we take the four-way shuttle system as the research object and establish the mathematical model of scheduling optimization based on the minimum time for the in/out operation optimization and path optimization scheduling problems of the four-way shuttle system. An improved genetic algorithm is used to solve the task planning, and an improved A* algorithm is used to solve the path optimization within the shelf level. The conflicts generated by the parallel operation of the four-way shuttle system are classified, and the improved A* algorithm based on the time window method is constructed for path optimization through the dynamic graph theory method to seek safe conflict-free paths. Through simulation example analysis, it is verified that the improved A* algorithm proposed in this paper has obvious optimization effect on the model of this paper.

Fruit texture and storage properties of various apple varieties exhibit significant variation. The rate of fruit softening post-harvest plays a crucial role in determining fruit quality and shelf life. This research utilized four apple varieties as test subjects to investigate the internal factors influencing fruit texture changes among different varieties. By monitoring changes in relevant physiological indicators during the post-harvest texture softening process, the study examined fruit quality, cell wall material content, hydrolase activity, and gene transcription levels during storage of ‘Orin’, ‘RX’, ‘RXH’, and ‘Envy’ apples. Initial fruit softening was primarily linked to heightened post-harvest fruit respiration intensity, ethylene production, and rapid amylase activity. Subsequent softening was associated with increased activity of water-soluble pectin (WSP), cellulose (CEL), and other hydrolases. With the extension of the storage period, the fruit cells of the four varieties became more loosely arranged, resulting in larger intercellular gaps. Variations in WSP and cellulose content, CEL activity, and relative expression of Mdβ-gal were observed among the different apple varieties, potentially accounting for the disparities in fruit texture.

In this paper, a cotton precision seed-taking dibbler device was designed to address the problems of congestion and leakage of the hole-type dibbler during high-speed operation (more than 4 km/h). Firstly, the motion trajectory of the seed in the limited gear-shaped space was analyzed and a motion model was established to analyze the relationship between the motion trajectory and seed-filling performance. Secondly, a central combination test with four factors and five levels was implemented using the discrete element software EDEM2018, which simulated the seed-filling performance of the seed-holding space with different structural dimensions. The optimal parameters impacting the seed-filling behavior of the designed dibbler were derived via response surface optimization and multiple regression analyses. Under optimal conditions, three bench tests were repeatedly conducted, and the average qualified index was 93.67%, the leakage index Y3 was 2.67%, and the multiple index Y2 was 3.66%, which was close to the simulation results. Finally, for the speed adaptability test of the seed-holding space with optimal structural parameters, the qualified index was more than 90% when the rotating speed ranged from 1.0 to 2.0 r/s (the speed of the corresponding dibbler was 5.4 km/h to 7.2 km/h), indicating that the dibbler could meet the requirements of high-speed operation and had good speed adaptability. The results can not only provide a reference for the development of precision hole-type dibblers but also have theoretical significance for the quantitative separation of the individual from the population of irregularly rotating agricultural materials and ore materials such as cotton seeds.

In light of recent advancements in synchrotron radiation technology and nano-technology, there has been a marked increase in the need for ultra-precision nano-positioning mechanisms. This paper presents a method that integrates physical models with multi-objective optimization for developing an optical angle nano-positioning mechanism. We begin by examining the actual motion law of the mechanism, based on kinematic principles. The outcomes from this kinematic analysis facilitate a static analysis of the flexible hinge, identified as a critical component of the mechanism. Subsequently, we establish a dynamic model for the entire mechanism. By employing the physical model as a base and combining it with the optimization algorithm, we identify the optimal design parameters for the mechanism. The design achieves a resolution of 50 nrad and meets the specified requirements. The first-order inherent frequency of the mechanism is approximately 43.75 Hz. There is a discrepancy of 2.63% from the finite element modal analysis results and a 3.33% difference from the theoretical analysis results, validating the reliability of the design method proposed in this study.

The decision-making algorithm serves as a fundamental component for advancing the level of autonomous driving. The end-to-end decision-making algorithm has a strong ability to process the original data, but it has grave uncertainty. However, other learning-based decision-making algorithms rely heavily on ideal state information and are entirely unsuitable for autonomous driving tasks in real-world scenarios with incomplete global information. Addressing this research gap, this paper proposes a stable hierarchical decision-making framework with images as the input. The first step of the framework is a model-based data encoder that converts the input image data into a fixed universal data format. Next is a state machine based on a time series Graph Convolutional Network (GCN), which is used to classify the current driving state. Finally, according to the state’s classification, the corresponding rule-based algorithm is selected for action generation. Through verification, the algorithm demonstrates the ability to perform autonomous driving tasks in different traffic scenarios without relying on global network information. Comparative experiments further confirm the effectiveness of the hierarchical framework, model-based image data encoder, and time series GCN.

The expansion tube is a promising energy absorption structure in spacecraft and airplanes, where it is often exposed to impact stress. Despite prior studies on the deformation mode of expansion tubes have been conducted, the majority of them have relied on quasi-static load. This research has utilized theoretical, computational, and experimental approaches to concentrate on the behaviors of expansion tubes exposed to dynamic impacts. The experimental results show that the strain-rate effect and the downward velocity discrepancy could even cause the deformation mode transition of the expansion tube. The dynamic theoretical model of steady-state expansion force is derived and used to predict the normalized compressive force. A normalized compressive force more than 0.85 would promote buckling deformation of the expansion tube. The normalized compressive force is then used to predict the deformation mode diagrams of the expansion tube for a range of geometric parameters; this analysis reveals that the semi-angle, expansion rate, and radius/wall-thickness of the tube all play a role in determining the deformation mode, while the effect of length/radius is less evident. The expansion tube's buckling resistance is enhanced by the parent material's strain rate sensitivity and diminished by the strain hardening effect.

Abstract Osteoarthritis (OA) is a complicated disorder that is the most prevalent chronic degenerative joint disease nowadays. Pudilan Tablets (PDL) is a prominent traditional Chinese medicine formula used in clinical settings to treat chronic inflammatory illnesses. However, there is currently minimal fundamental research on PDL in the therapy of joint diseases. As a result, this study looked at the anti-inflammatory and anti-OA properties of PDL in vitro and in vivo, as well as the mechanism of PDL in the treatment of OA. We investigated the anti-OA properties of PDL in OA mice that were generated by monosodium iodoacetate (MIA). All animals were administered PDL (2 g/kg or 4 g/kg) or the positive control drug, indomethacin (150 mg/kg), once daily for a total of 28 days starting on the day of MIA injection. The CCK-8 assay was used to test the vitality of PDL-treated RAW264.7 cells in vitro. RAW264.7 cells that had been activated with lipopolysaccharide (LPS) were used to assess the anti-inflammatory properties of PDL. In the MIA-induced OA model mice, PDL reduced pain, decreased OA-induced cartilage damages and degradation, decreased production of pro-inflammatory cytokines in serum, and suppressed IL-1β, IL-6, and TNF-α mRNA expression levels in tibiofemoral joint. In RAW264.7 cells, PDL treatment prevented LPS-induced activation of the ERK/Akt signaling pathway and significantly decreased the levels of inflammatory cytokines, such as IL-1β, IL-6, and TNF-α. In conclusion, these results suggest that PDL is involved in combating the development and progression of OA, exerts a powerful anti-inflammatory effect on the knee joint, and may be a promising candidate for the treatment of OA.

In this paper, we aim at the traffic sign detection and recognition in complex road conditions. We proposed a deep model for traffic sign detection and recognition. There are a few difficulties in traffic sign detection task, such as, less recognizable, small target size, easily leading to detected failure and so on. First, for the failure detection, we introduce Coordinate Attention (CA); second, to accelerate the regression of prediction box, we introduce the angle loss into our objective function; third, for the overlapping and occlusion phenomenon of ground truth, a dynamic label assignment strategy- simple Optimal Transport Assignment (SimOTA) is utilized during label assignment; the last and the most important, for the target size problem, we propose a feature fusion network, named hierarchical-path feature fusion network (H-PFANet). Experiments were conducted on two public data sets, the results show that our improved model performed better than YOLOv5s which is the base model and other popular algorithms on precision, recall and mAP. For the difficult samples in data set CCTSDB-2021, the results show that compared to YOLOv5s, the mAP@0.5 is improved by 6.3%, the mAP@0.5: 0.95 is improved by 5.3%, and our method achieved a detection speed of 91 FPS, with better robustness to changes in various traffic scenes, while maintaining the volume of the original YOLOv5s model. On the whole CCTSDB-2021 data set, the precision of our model reached 98.1%, the recall of our model reached 97.6% and the mAP@0.5 reached 98.8% with a speed of 91 FPS. We also compared our method with other current detection algorithms on TT100K data set, the results show that our proposed method performed better, and show the effectiveness of our method.

Abstract Background Alzheimer’s disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, facilitates fatty acid oxidation in the mitochondria, and alleviates oxidative stress. Methods Here, we designed a randomised, double-blinded, placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients. One-dose CMA included 12.35 g L-serine (61.75%), 1 g nicotinamide riboside (5%), 2.55 g N-acetyl-L-cysteine (12.75%), and 3.73 g L-carnitine tartrate (18.65%). AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84. The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients. Results We showed a significant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P = 0.00001, 29% improvement) in the CMA group. Moreover, there was a significant decline (P = 0.0073) in ADAS-Cog scores (improvement of cognitive functions) in the CMA compared to the placebo group in patients with higher ADAS-Cog scores. Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis. Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism were significantly improved after CMA treatment. Conclusion Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis. Trial registration ClinicalTrials.gov NCT04044131 Registered 17 July 2019, https://clinicaltrials.gov/ct2/show/NCT04044131

Abstract Background Tourniquets provide better tissue visibility during arthroscopic surgery. However, multiple postoperative adverse events associated with ischemia may be caused by excessive inflation pressure and duration. We aimed to evaluate the degree of tourniquet-induced ischemia using a noninvasive continuous real-time monitoring method and the relationship between changes in tissue oxygen saturation (StO2) and blood biochemical markers of ischemic injuries in patients undergoing arthroscopic knee surgery. Methods This was a prospective observational study using near-infrared spectroscopy (NIRS). Data were collected from 29 consecutive patients who underwent arthroscopic procedures. Twenty-five patients underwent anterior cruciate ligament reconstruction, and four underwent meniscal repair. We investigated tourniquet‐induced changes in StO2, monitored using NIRS, and blood biochemical markers of ischemic injuries. Results A significant decrease in the mean StO2 from the baseline was observed during tourniquet inflation in the operative legs. The average decrease in the mean StO2 was 58%. A comparison of mean StO2 between the nonoperative and operative legs before tourniquet deflation showed that mean values of StO2 in the operative legs were significantly lower than those in the nonoperative legs. No significant clinical relationships were observed between changes in StO2 and blood biochemical markers of ischemic injuries (creatine kinase) (p = 0.04, r = 0.38) or tourniquet duration (p = 0.05, r = 0.366). Conclusions Our results demonstrated that StO2 could be used to evaluate tissue perfusion in real time but did not support the hypothesis that StO2 is a useful method for predicting the degree of tourniquet-induced injury during arthroscopic knee surgery.

Abstract Background Hepatocellular carcinoma (HCC) belongs to a representative lethality gastrointestinal malignancy, and comprehensive management of HCC remains intractable at present on account of its invasive biological feature that is easy to relapse and early metastasis. The intimate connection between platelets and tumor progression has been widely reported, and platelet-related indicators are also used in the clinical practice of carcinoma. This work is designed to investigate the significance of platelet-related genes in the prognostic prediction of patients with HCC and their potential role in the cross-talk between HCC cells and platelets in the tumor microenvironment. Methods By integrating the RNA-seq data and clinicopathological information of HCC patients, we extracted prognosis-associated platelet-related genes based on the univariate cox analysis and further established a relevant prognostic signature via the lasso cox regression analysis, and two independent HCC cohorts were used as external validation. Multiple bioinformatics methods were utilized to explore the underlying functional discrepancy between different risk groups classified by the risk model. And in vitro proliferation, invasion, and migration assays were conducted to investigate the effect of platelet stimulation on HCC cells’ viability and motility, and flow cytometric analysis was exerted to demonstrate the influence of HCC cells on platelet activation. Results A novel platelet-related risk model was developed and patients both in the training and testing cohorts were divided into distinct risk subgroups according to the median risk score. It was observed that the high-risk status was closely associated with poor prognosis and worse clinicopathological parameters. Meanwhile, an obvious discrepancy in the constitution of the immune microenvironment also indicated that distinct immune status might be a potential determinant affecting prognosis as well as immunotherapy reactiveness. Moreover, in vitro experiments demonstrated that PRKCD could act as a molecular bridge between tumor cells and platelets, which could either participate in regulating tumor malignant phenotype or mediating platelet activation. Conclusions In brief, this work reveals a novel platelet-related risk signature for prognostic evaluation of HCC patients and confirms that PRKCD is a key messenger in HCC cell-platelet interaction and plays a crucial role in mediating platelet-induced tumor progression.

Abstract Unrestricted reproduction and spread of pest had caused great damage to the quality and yield of crops in recent years. Besides the use of traditional chemical pesticides, natural products also make a huge contribution against pests. Chasmanthinine, a diterpenoid alkaloid isolated from Aconitum franchetii var. villosulum, shown extremely antifeedant activity against Spodoptera exigua. Therefore, a series of novel Chasmanthinine derivatives were synthesized and their biological activity was studied in this work. Compound 33 showed the strongest antifeedant activity (EC50 = 0.10 mg/cm2) among all the test compounds. The mechanism research of 33 revealed that its antifeedant effect was related to the inhibition of carboxylesterase (CES), and proved the thiophene acyl group could form a strong binding effect with CES by molecular docking. Moreover, compound 10 exhibited the strongest cytotoxicity (IC50 = 12.87 μM) against Sf9 cell line and moderate contact toxicity. The mechanism research indicated that compound 10 could induce Sf9 cells apoptosis. In summary, the results lay a foundation for the application of diterpene alkaloids in plant protection.

ABSTRACT: China is the kingdom of arch bridges. Based on the principle of structural elastic potential energy standing value, the innovative application of the design theory of composite arch bridge bending and compression is presented, optimize the design of composite structural arch bridge arch axis, and propose the design and construction method of medium-bearing composite Nielsen arch bridge. The design of the medium-bearing composite Nielsen arch bridge is carried out, its structural strength, stiffness and stability are analyzed by finite element analysis. By simulating the parameters of arch axis, sagittal span ratio and arch section, the convergent composite arch axis with solid web foot section is adopted to improve the economic spanning capacity of the composite Nielsen arch bridge and expand the adaptation range of large span arch bridge in plain area or soft base area

ABSTRACT: This essay proposes a new structural system for a large span three-arch, three-cable face steel edge main beamrigid tie composite arch bridge. The authors invented a new structural form of a steel edge main girder rigid tie, and developed and designed a key arch-bar three-dimensional six-way space node structure. The analysis of results show that: compared with the traditional arch bridge, the large span three-arch three-cable face steel-sided main beam rigid ties composite arch bridgeis beautiful in shape, hasareasonable structure and efficient construction. It is a high-strength, high-performance composite structural system, with better strength, stiffness, stability and dynamic performance, which overcomes the large span ultra-wide bridge deck arch bridge horizontal thrust, poor transverse stability, and the key technical problems of acable joint control. The proposed structural form has a wide range of engineering application prospects

Attention-deficit hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder that affects approximately 5.3% of children and approximately 2.5% of adults. There is an intimate relationship between ADHD and sleep disturbance. Specifically, individuals carry a mutation in the core circadian gene CRY1 (c. 1657 + 3A > C), which results in the deletion of exon 11 expression in the CRY1 protein (CRY1Δ11), causing them to exhibit typical ADHD symptoms. However, the underlying mechanism is still elusive. In this study, we demonstrate that Cry1Δ11 (c. 1717 + 3A > C) mice showed ADHD-like symptoms, including hyperactivity, impulsivity, and deficits in learning and memory. A hyperactive cAMP signaling pathway was found in the nucleus accumbens (NAc) of Cry1Δ11 mice. We further demonstrated that upregulated c-Fos was mainly localized in dopamine D1 receptor-expressing medium spiny neurons (DRD1-MSNs) in the NAc. Neuronal excitability of DRD1-MSNs in the NAc of Cry1Δ11 mice was significantly higher than that of WT controls. Mechanistically, the CRY1Δ11 protein, in contrast to the WT CRY1 protein, failed to interact with the Gαs protein and inhibit DRD1 signaling. Finally, the DRD1 antagonist SCH23390 normalized most ADHD-like symptoms in Cry1Δ11 mice. Thus, our results reveal hyperactive DRD1 signaling as an underlying mechanism and therapeutic target for ADHD induced by the highly prevalent CRY1Δ11 mutation.

Major Histocompatibility Complex Class II (MHC II) deficiency is a rare primary immunodeficiency disorder (PID) with autosomal recessive inheritance pattern. The outcome is almost fatal owing to delayed diagnosis and lacking of effective therapy. Therefore, prompt diagnosis, timely and effective treatment are critical. Here, we report a 117-day-old boy with diarrhea, cough, cyanosis and tachypnea who was failed to be cured by empiric antimicrobial therapy initially and progressed to severe pneumonia and respiratory failure. The patient was admitted to the pediatric intensive care unit (PICU) immediately and underwent a series of tests. Blood examination revealed elevated levels of inflammatory markers and cytomegalovirus DNA. Imaging findings showed signs of severe infection of lungs. Finally, the diagnosis was obtained mainly through next-generation sequencing (NGS). We found out what pathogenic microorganism he was infected via repeated conventional detection methods and metagenomic next-generation sequencing (mNGS) of sputum and bronchoalveolar lavage fluid (BALF). And his whole exome sequencing (WES) examination suggested that CIITA gene was heterozygous mutation, a kind of MHC II deficiency diseases. After aggressive respiratory support and repeated adjustment of antimicrobial regimens, the patient was weaned from ventilator on the 56th day of admission and transferred to the immunology ward on the 60th day. The patient was successful discharged after hospitalizing for 91 days, taking antimicrobials orally to prevent infections post-discharge and waiting for stem cell transplantation. This case highlights the potential importance of NGS in providing better diagnostic testing for unexplained infection and illness. Furthermore, pathogens would be identified more accurately if conventional detection techniques were combined with mNGS.

Background Poor pain control and opioid use are risk factors for perioperative neurocognitive disorders (PND). The peripheral nerve block (PNB) can reduce pain and opioid consumption. This systematic review aimed to investigate the effects of PNB on PND in older patients with hip fractures. Methods The PubMed, Cochrane Central Registers of Controlled Trial, Embase and ClinicalTrials.gov databases were searched from inception until November 19, 2021 for all randomized controlled trials (RCTs) comparing PNB with analgesics. The quality of the selected studies was assessed according to Version 2 of the Cochrane tool for assessing the risk of bias in RCTs. The primary outcome was the incidence of PND. Secondary outcomes included pain intensity and the incidence of postoperative nausea and vomiting. Subgroup analyses were based on population characteristics, type and infusion method of local anesthetics, and type of PNB. Results Eight RCTs comprising 1015 older patients with hip fractures were included. Compared with analgesics, PNB did not reduce the incidence of PND in the elderly hip fracture population comprising patients with intact cognition and those with pre-existing dementia or cognitive impairment (risk ratio [RR] = .67; 95% confidence interval [CI] = .42 to 1.08; P = .10; I 2 = 64%). However, PNB reduced the incidence of PND in older patients with intact cognition (RR = .61; 95% CI = .41 to .91; P = .02; I 2 = 0%). Fascia iliaca compartment block, bupivacaine, and continuous infusion of local anesthetics were found to reduce the incidence of PND. Conclusions PNB effectively reduced PND in older patients with hip fractures and intact cognition. When the study population included patients with intact cognition and those with pre-existing dementia or cognitive impairment, PNB showed no reduction in the incidence of PND. These conclusions should be confirmed with larger, higher-quality RCTs.

IntroductionGut microbiota reportedly play a critical role in some autoimmune diseases by maintaining immune homeostasis. Only a few studies have examined the correlation between gut microbiota and the onset of primary immune thrombocytopenia (ITP), especially in children. The purpose of this study was to investigate changes in the composition and diversity of the fecal microbiota of children with ITP, as well as the correlation between such microbiota and the onset of ITP.MethodsTwenty-five children newly diagnosed with ITP and 16 healthy volunteers (controls) were selected for the study. Fresh stool samples were collected to identify changes in the composition and diversity of gut microbiota as well as for potential correlation analysis.ResultsIn ITP patients, the phyla that were most frequently encountered were Firmicutes (54.3%), followed by Actinobacteria (19.79%), Bacteriodetes (16.06%), and Proteobacteria (8.75%). The phyla that were predominantly found in the controls were, Firmicutes (45.84%), Actinobacteria (40.15%), Bacteriodetes (3.42%), and Proteobacteria (10.23%). Compared with those of the controls, the proportions of Firmicutes and Bacteriodetes in the gut microbiota of ITP patients were increased while the proportions of Actinobacteria and Proteobacteria were decreased. Furthermore, gut microbiota in ITP patients varied by age group, showed specific changes in diversity, and were correlated with antiplatelet antibodies. IgG levels were significantly positively correlated with Bacteroides (P

The cultivation of poplar trees is hindered by persistent cropping challenges, resulting in reduced wood productivity and increased susceptibility to soil-borne diseases. These issues primarily arise from alterations in microbial structure and the infiltration of pathogenic fungi. To investigate the impact on soil fertility, we conducted an analysis using soil samples from both perennial poplar trees and three successive generations of continuously cropped poplar trees. The quantity and community composition of bacteria and fungi in the rhizosphere were assessed using the Illumina MiSeq platform. The objective of this study is to elucidate the impact of continuous cropping challenges on soil fertility and rhizosphere microorganisms in poplar trees, thereby establishing a theoretical foundation for investigating the mechanisms underlying these challenges. The study found that the total bacteria in the BT group is 0.42 times higher than the CK group, and the total fungi is 0.33 times lower than the CK group. The BT and CK groups presented relatively similar bacterial richness and diversity, while the indices showed a significant (p < 0.05) higher fungal richness and diversity in the CK group. The fractions of Bacillus were 2.22% and 2.41% in the BT and CK groups, respectively. There was a 35.29% fraction of Inocybe in the BT group, whereas this was barely observed in the CK group. The fractions of Geopora were 26.25% and 5.99%, respectively in the BT and CK groups. Modifying the microbial community structure in soil subjected to continuous cropping is deemed as the most effective approach to mitigate the challenges associated with this agricultural practice.

Abstract Background The comprehensive geriatric assessment (CGA) has been proposed as a supplementary tool to reduce perioperative complications of geriatric patients, however there is no universally accepted standardization of CGA for orthopedic surgery. In this study, a novel CGA strategy was applied to evaluate the conditions of older patients undergoing orthopedic surgery from a broad view and to identify potential risk factors for postoperative complications. Methods A prospective cohort study was conducted from March 2019 to December 2020.The study enrolled patients (age > 75 years) for elective or confined orthopedic surgery. All patients were treated by a multidisciplinary team. A structured CGA was conducted to identify high-risk older patients and to facilitate coordinated multidisciplinary team care by a geriatric team. The basic patient characteristics, CGA results, postoperative complication and mortality rates were collected. Multivariate logistic regression analysis was used to identify risk factors for postoperative complications. Results A total of 214 patients with an age of 81.07 ± 4.78 (range, 75–100) years were prospectively enrolled in this study. In total, 66 (30.8%) complications were registered, including one death from myocardial infarction (mortality rate, 0.5%). Poor Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) were accompanied by frailty, worse perioperative risk, pain, and nutritional status. Poor ADL was also associated with higher risks of falling, polypharmacy, and cardiac and respiration complications. Poor IADL was associated with a higher risk of cardiac and respiration complications. Higher stroke risk was accompanied by higher risks of cardiac complications, delirium, and hemorrhage. Worse American Society of Anesthesiologists (ASA) score was associated with worse ADL, IADL, frailty, and higher delirium risk. Multivariate logistic regression analysis showed that spinal fusion (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.65 to 0.83; p = 0.0214), blood loss(OR, 1.68; 95% CI, 1.31 to 2.01; p = 0.0168), ADL (severe dysfunction or worse) (OR, 1.45; 95% CI, 1.16 to 1.81; p = 0.0413), IADL (serious dependence) (OR, 1.08; 95% CI, 1.33 to 1.63; p = 0.0436), renal function (chronic kidney disease (CKD) ≥ stage 3a) (OR, 2.01; 95% CI, 1.54 to 2.55; p = 0.0133), and malnutrition(OR, 2.11; 95% CI, 1.74 to 2.56; p = 0.0101) were independent risk factors for postoperative complications. Conclusion The CGA process reduces patient mortality and increases safety in older orthopedic surgery patients. Spinal fusion, blood loss, ADL (severe dysfunction or worse), IADL (serious dependence), renal function (CKD ≥ stage 3a) and nutrition mini nutritional assessment (MNA) (malnourished) were independent risk factors of postoperative complications following orthopaedic surgery in older patients.

Abstract Biophysical models contain a large number of parameters, while the spiking characteristics of neurons are related to a few key parameters. For thalamic neurons, relay reliability is an important characteristic that affects Parkinson's state. This paper proposes a method to fit key parameters of the model based on the spiking characteristics of neurons, and improves the traditional particle swarm optimization algorithm. That is, a nonlinear concave function and a Logistic chaotic mapping are combined to adjust the inertia weight of particles to avoid the particle falling into a local optimum in the search process or appearing premature convergence. In this paper, three parameters that play an important role in Parkinson's state of the thalamic cell model are selected and fitted by the improved particle swarm optimization algorithm. Using the fitted parameters to reconstruct the neuron model can predict the spiking trajectories well, which verifies the effectiveness of the fitting method. By comparing the fitting results with other particle swarm optimization algorithms, it is shown that the proposed particle swarm optimization algorithm can better avoid local optima and converge to the optimal values quickly.

Abstract Background Studies have shown that long noncoding RNAs and N6-methyladenosine play important roles in gastric cancer. The purpose of this study was to determine the correlation and prognostic value of m6A-related lncRNAs and immune infiltration in gastric cancer. Methods We downloaded the clinically related information and RNA-Seq transcriptome data of gastric cancer patients from the TCGA database. Univariate Cox regression analysis and Pearson analysis were used to screen out m6A-related lncRNAs. Consensus cluster analysis was used to divide the sample into two clusters, and LASSO analysis and Cox regression analysis were used to construct a risk scoring model. Results A total of 25 lncRNA expression profiles were screened, and gastric cancer patients were divided into different subtypes. Cluster 2 had a better prognosis, but its stromal score, ESTIMATE score and immune score were low. Cluster 1 was rich in resting memory CD4 T cells, regulatory T cells, monocytes, and resting mast cells, and Cluster 2 was rich in activated memory CD4 T cells and follicular helper T cells. Thirteen lncRNAs were selected to construct a risk model, and the prognosis of gastric cancer patients in the high-risk group was poor. The expression of PD-L1 in tumours is significantly higher than that in normal tissues. Univariate and multivariate Cox regression analysis results showed that the overall survival rate was significantly related to stage and the risk score, which can be used as an independent prognostic factor. The results of the heatmap and scatter plot showed that clusters (P = 0.0045) and grade (G1–2, G3, P = 0.0037) were significantly related to prognosis. The relationship between the risk score and immune cell infiltration showed that memory B cells, resting dendritic cells, M0 macrophages, and M2 macrophages were positively correlated with the risk score, while resting mast cells, monocytes, activated NK cells, and follicular helper T cells were negatively correlated with the risk score. Conclusion The results of this study indicate that m6A-related lncRNAs may play an important role in the prognosis of gastric cancer patients and the tumour immune microenvironment and may provide help for the treatment of gastric cancer patients.