TMPRSS2 is a tumor suppressor and its downregulation promotes antitumor immunity and immunotherapy response in lung adenocarcinoma.

BACKGROUND: TMPRSS2, a key molecule for SARS-CoV-2 invading human host cells, has an association with cancer. However, its association with lung cancer remains insufficiently unexplored. METHODS: In five bulk transcriptomics datasets, one single-cell RNA sequencing (scRNA-seq) dataset and one proteomics dataset for lung adenocarcinoma (LUAD), we explored associations between TMPRSS2 expression and immune signatures, tumor progression phenotypes, genomic features, and clinical prognosis in LUAD by the bioinformatics approach. Furthermore, we performed experimental validation of the bioinformatics findings. RESULTS: TMPRSS2 expression levels correlated negatively with the enrichment levels of both immune-stimulatory and immune-inhibitory signatures, while they correlated positively with the ratios of immune-stimulatory/immune-inhibitory signatures. It indicated that TMPRSS2 levels had a stronger negative correlation with immune-inhibitory than with immune-stimulatory signatures. TMPRSS2 downregulation correlated with increased proliferation, stemness, genomic instability, tumor progression, and worse survival in LUAD. We further validated that TMPRSS2 was downregulated with tumor progression in the LUAD cohort we collected from Jiangsu Cancer Hospital, China. In vitro and in vivo experiments verified the association of TMPRSS2 deficiency with increased tumor cell proliferation and invasion and antitumor immunity in LUAD. Moreover, in vivo experiments demonstrated that TMPRSS2-knockdown tumors were more sensitive to BMS-1, an inhibitor of PD-1/PD-L1. CONCLUSIONS: TMPRSS2 is a tumor suppressor, while its downregulation is a positive biomarker of immunotherapy in LUAD. Our data provide a potential link between lung cancer and pneumonia caused by SARS-CoV-2 infection.

MRI Deep Learning-Based Automatic Segmentation of Interventricular Septum for Black-Blood Myocardial T2* Measurement in Thalassemia.

BACKGROUND: The T2* value of interventricular septum is routinely reported for grading myocardial iron load in thalassemia major, and automatic segmentation of septum could shorten analysis time and reduce interobserver variability. PURPOSE: To develop a deep learning-based method for automatic septum segmentation from black-blood MR images for the myocardial T2* measurement of thalassemia patients. STUDY TYPE: Retrospective. POPULATION/SUBJECTS: One hundred forty-six transfusion-dependent thalassemia patients with cardiac MR examinations from two centers. Data from Center 1 (1.5 T) were assigned to the training (100 examinations) and internal testing (20 examinations) sets; data from Center 2 were assigned to the external testing set (26 examinations; 10 at 1.5 T and 16 at 3.0 T). FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T, multiecho gradient-echo sequence. ASSESSMENT: A modified attention U-Net for septum segmentation was constructed and trained, and its performance evaluated on unseen internal and external datasets. T2* was measured by fitting the average septum signal, separately segmented by automatic and manual methods. STATISTICAL TESTS: Agreement between manual and automatic septum segmentations was assessed with the Dice coefficient, and T2* agreement was assessed using the Bland-Altman plot and the coefficient of variation (CoV). RESULTS: The median Dice coefficient of deep network-based septum segmentation was 0.90 [0.05] on the internal dataset, 0.82 [0.10] on the external 1.5 T dataset, and 0.86 [0.14] on the external 3.0 T dataset. T2* measurements using automatic segmentation corresponded with those from manual segmentation, with a mean difference of 0.02 (95% LoA: -0.74 to 0.79) msec, 0.43 (95% LoA: -2.1 to 3.0) msec, and 0.36 (95% LoA: -0.72 to 1.4) msec on the three datasets. The CoVs between the two methods were 3.1%, 7.0%, and 6.1% on the internal and two external datasets, respectively. DATA CONCLUSIONS: The proposed septum segmentation yielded myocardial T2* measurements which were highly consistent with those obtained by manual segmentation. This automatic approach may facilitate data processing and avoid operator-dependent variability in practice. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 1.

Diffusion-weighted magnetic resonance imaging in rat kidney using two-dimensional navigated, interleaved echo-planar imaging at 7.0 T.

The purpose of this study was to investigate the feasibility of two-dimensional (2D) navigated, interleaved multishot echo-planar imaging (EPI) to enhance kidney diffusion-weighted imaging (DWI) in rats at 7.0 T. Fully sampled interleaved four-shot EPI with 2D navigators was tailored for kidney DWI (Sprague-Dawley rats, n = 7) on a 7.0-T small bore preclinical scanner. The image quality of four-shot EPI was compared with T2 -weighted rapid acquisition with relaxation enhancement (RARE) (reference) and single-shot EPI (ss-EPI) without and with parallel imaging (PI). The contrast-to-noise ratio (CNR) was examined to assess the image quality for the EPI approaches. The Dice similarity coefficient and the Hausdorff distance were used for evaluation of image distortion. Mean diffusivity (MD) and fractional anisotropy (FA) were calculated for renal cortex and medulla for all DWI approaches. The corticomedullary difference of MD and FA were assessed by Wilcoxon signed-rank test. Four-shot EPI showed the highest CNR among the three EPI variants and lowest geometric distortion versus T2 -weighted RARE (mean Dice: 0.77 for ss-EPI without PI, 0.88 for ss-EPI with twofold undersampling, and 0.92 for four-shot EPI). The FA map derived from four-shot EPI clearly identified a highly anisotropic region corresponding to the inner stripe of the outer medulla. Four-shot EPI successfully discerned differences in both MD and FA between renal cortex and medulla. In conclusion, 2D navigated, interleaved multishot EPI facilitates high-quality rat kidney DWI with clearly depicted intralayer and interlayer structure and substantially reduced image distortion. This approach enables the anatomic integrity of DWI-MRI in small rodents and has the potential to benefit the characterization of renal microstructure in preclinical studies.

AGR2-induced cholesterol synthesis drives lovastatin resistance that is overcome by combination therapy with allicin.

Anterior gradient 2 (AGR2), a protein disulfide isomerase (PDI), is a multifunctional protein under physiological and pathological conditions. In this study we investigated the roles of AGR2 in regulating cholesterol biogenesis, lipid-lowering efficiency of lovastatin as well as in protection against hypercholesterolemia/statin-induced liver injury. We showed that AGR2 knockout significantly decreased hepatic and serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in mice with whole-body or hepatocyte-specific Agr2-null mutant, compared with the levels in their wild-type littermates fed a normal chow diet (NCD) or high-fat diet (HFD). In contrast, mice with AGR2 overexpression (Agr2/Tg) exhibited an increased cholesterol level. Mechanistic studies revealed that AGR2 affected cholesterol biogenesis via activation of AKT/sterol regulatory element-binding protein-2 (SREBP2), to some extent, in a PDI motif-dependent manner. Moreover, elevated AGR2 led to a significant decrease in the lipid-lowering efficacy of lovastatin (10 mg· kg-1· d-1, ip, for 2 weeks) in mice with hypercholesterolemia (hyperCho), which was validated by results obtained from clinical samples in statin-treated patients. We showed that lovastatin had limited effect on AGR2 expression, but AGR2 was inducible in Agr2/Tg mice fed a HFD. Further investigations demonstrated that drug-induced liver toxicity and inflammatory reactions were alleviated in hypercholesterolemic Agr2/Tg mice, suggesting the dual functions of AGR2 in lipid management and hyperCho/statin-induced liver injury. Importantly, the AGR2-reduced lipid-lowering efficacy of lovastatin was attenuated, at least partially, by co-administration of a sulfhydryl-reactive compound allicin (20 mg· kg-1· d-1, ip, for 2 weeks). These results demonstrate a novel role of AGR2 in cholesterol metabolism, drug resistance and liver protection, suggesting AGR2 as a potential predictor for selection of lipid-lowering drugs in clinic.

Characterizing potential repelling volatiles for "push-pull" strategy against stem borer: a case study in Chilo auricilius.

BACKGROUND: Massive techniques have been evaluated for developing different pest control methods to minimize fertilizer and pesticide inputs. As "push-pull" strategy utilizes generally non-toxic chemicals to manipulate behaviors of insects, such strategy is considered to be environmentally friendly. "Push-pull" strategy has been extraordinarily effective in controlling stem borers, and the identification of new "pushing" or "pull" components against stem borers could be significantly helpful. RESULTS: In this study, the results of field trapping assay and behavioral assay showed the larvae of C.auricilius, one kind of stem borers, could be deterred by rice plant under tilling stage, its main host crop. The profiles of volatiles were compared between rice plants under two different developmental stages, and α-pinene was identified as a key differential component. The repelling activity of α-pinene against C.auricilius was confirmed by Y-tube olfactometer. For illuminating the olfactory recognition mechanism, transcriptome analysis was carried out, and 13 chemosensory proteins (CSPs) were identified in larvae and 19 CSPs were identified in adult of C.auriciliu, which was reported for the first time in this insect. Among these identified CSPs, 4 CSPs were significantly regulated by α-pinene treatment, and CSP8 showed good binding affinity with α-pinene in vitro. CONCLUSIONS: Overall, C.auricilius could be repelled by rice plant at tilling stage, and our results highlighted α-pinene as a key component in inducing repelling activity at this specific stage and confirmed the roles of some candidate chemosensory elements in this chemo-sensing process. The results in this study could provide valuable information for chemosensory mechanism of C.auricilius and for identification of "push" agent against rice stem borers.

CD109 regulates the inflammatory response and is required for the pathogenesis of rheumatoid arthritis.

OBJECTIVE: The aim of this study was to investigate the role of CD109 in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) and to evaluate its potential as a therapeutic target. METHODS: CD109 expression was examined in synovial tissues and FLSs from RA patients and collagen-induced arthritis (CIA) model mice. CD109-deficient mice were developed to evaluate the severity of CIA. Small interfering RNAs and a neutralising antibody against CD109 (anti-CD109) were designed for functional or treatment studies in RA FLSs and CIA. RESULTS: CD109 was found to be abundantly expressed in the synovial tissues from RA patients and CIA mice. CD109 expression in RA FLSs was upregulated by inflammatory stimuli, such as interleukin-1ß and tumour necrosis factor-α. Silencing of CD109 or anti-CD109 treatment reduced proinflammatory factor production, cell migration, invasion, chemoattractive potential and osteoclast differentiation, thereby reducing the deleterious inflammatory response of RA FLSs in vitro. Mice lacking CD109 were protected against arthritis in the CIA model. Anti-CD109 treatment prevented the onset and ameliorated the severity of CIA lesions. CONCLUSION: Our study uncovers an antiarthritic role for CD109 and suggests that CD109 inhibition might serve as a promising novel therapeutic strategy for RA.

Efficient derivation of dopaminergic neurons from SOX1⁻ floor plate cells under defined culture conditions.

BACKGROUND: Parkinson's disease (PD) is a severe neurodegenerative disease associated with loss of dopaminergic neurons. Derivation of dopaminergic neurons from human embryonic stem cells (hESCs) could provide new therapeutic options for PD therapy. Dopaminergic neurons are derived from SOX(-) floor plate (FP) cells during embryonic development in many species and in human cell culture in vitro. Early treatment with sonic hedgehog (Shh) has been reported to efficiently convert hESCs into FP lineages. METHODS: In this study, we attempted to utilize a Shh-free approach in deriving SOX1(-) FP cells from hESCs in vitro. Neuroectoderm conversion from hESCs was achieved with dual inhibition of the BMP4 (LDN193189) and TGF-ß signaling pathways (SB431542) for 24 h under defined culture conditions. RESULTS: Following a further 5 days of treatment with LDN193189 or LDN193189 + SB431542, SOX1(-) FP cells constituted 70-80 % of the entire cell population. Upon treatment with Shh and FGF8, the SOX1(-) FP cells were efficiently converted to functional Nurr1(+) and TH(+) dopaminergic cells (patterning), which constituted more than 98 % of the entire cell population. However, when the same growth factors were applied to SOX1(+) cells, only less than 4 % of the cells became Nurr1(+), indicating that patterning was effective only if SOX1 expression was down-regulated. After transplanting the Nurr1(+) and TH(+) cells into a hemiparkinsonian rat model, significant improvements were observed in amphetamine induced ipslateral rotations, apomorphine induced contra-lateral rotations and Rota rod motor tests over a duration of 8 weeks. CONCLUSIONS: Our findings thus provide a convenient approach to FP development and functional dopaminergic neuron derivation.

A model-based MR parameter mapping network robust to substantial variations in acquisition settings.

Deep learning methods show great potential for the efficient and precise estimation of quantitative parameter maps from multiple magnetic resonance (MR) images. Current deep learning-based MR parameter mapping (MPM) methods are mostly trained and tested using data with specific acquisition settings. However, scan protocols usually vary with centers, scanners, and studies in practice. Thus, deep learning methods applicable to MPM with varying acquisition settings are highly required but still rarely investigated. In this work, we develop a model-based deep network termed MMPM-Net for robust MPM with varying acquisition settings. A deep learning-based denoiser is introduced to construct the regularization term in the nonlinear inversion problem of MPM. The alternating direction method of multipliers is used to solve the optimization problem and then unrolled to construct MMPM-Net. The variation in acquisition parameters can be addressed by the data fidelity component in MMPM-Net. Extensive experiments are performed on R2 mapping and R1 mapping datasets with substantial variations in acquisition settings, and the results demonstrate that the proposed MMPM-Net method outperforms other state-of-the-art MR parameter mapping methods both qualitatively and quantitatively.

A fully automatic parenchyma extraction method for MRI T2* relaxometry of iron loaded liver in transfusion-dependent patients.

PURPOSE: To develop a fully automatic parenchyma extraction method for the T2* relaxometry of iron overload liver. METHODS: A retrospective multicenter collection of liver MR examinations from 177 transfusion-dependent patients was conducted. The proposed method extended a semiautomatic parenchyma extraction algorithm to a fully automatic approach by introducing a modified TransUNet on the R2* (1/T2*) map for liver segmentation. Axial liver slices from 129 patients at 1.5 T were allocated to training (85%) and internal test (15%) sets. Two external test sets separately included 1.5 T data from 20 patients and 3.0 T data from 28 patients. The final T2* measurement was obtained by fitting the average signal of the extracted liver parenchyma. The agreement between T2* measurements using fully and semiautomatic parenchyma extraction methods was assessed using coefficient of variation (CoV) and Bland-Altman plots. RESULTS: Dice of the deep network-based liver segmentation was 0.970 ± 0.019 on the internal dataset, 0.960 ± 0.035 on the external 1.5 T dataset, and 0.958 ± 0.014 on the external 3.0 T dataset. The mean difference bias between T2* measurements of the fully and semiautomatic methods were separately 0.12 (95% CI: -0.37, 0.61) ms, 0.04 (95% CI: -1.0, 1.1) ms, and 0.01 (95% CI: -0.25, 0.23) ms on the three test datasets. The CoVs between the two methods were 4.2%, 4.8% and 2.0% on the internal test set and two external test sets. CONCLUSIONS: The developed fully automatic parenchyma extraction approach provides an efficient and operator-independent T2* measurement for assessing hepatic iron content in clinical practice.

Efficacy of Repetitive Transcranial Magnetic Stimulation over the Supplementary Motor Area on Motor Function in Parkinson's Disease: A Meta-Analysis.

OBJECTIVES: The objective of this study was to assess the effect of repetitive transcranial magnetic stimulation (rTMS) on the supplementary motor area (SMA) in motor function in Parkinson's disease (PD) patients. METHOD: Databases searched included 5 databases from October 7,2022 to January 4, 2023. The Cochrane Bias Risk Assessment Tool was used for quality assessment. Standardized mean differences (SMDs) were calculated using a random-effects model. Outcome measure is the motor function examination of the motor part of Unified Parkinson's Disease Rating Scale (UPDRS-III). RESULTS: Seven studies totaling 374 patients were included. Meta-analysis showed that stimulation of SMA significantly improved motor function in PD patients compared with sham stimulation (SMD = -1.24; 95% CI, -2.24 to -0.24; P = 0.02; I 2 = 93%). Stimulation of the same target (SMA), subgroup analysis showed that high-frequency rTMS (HF-rTMS) is more effective than low-frequency rTMS (LF-rTMS) in improving motor function in PD (SMD = -1.39; 95% CI, -2.21 to -0.57; P = 0.04; I 2 = 77.2%). CONCLUSIONS: Overall, rTMS over SMA had a statistically significant improvement in motor function in PD patients, and HF-rTMS is statistically significantly more effective than LF-rTMS.

Spherical harmonics-based deep learning achieves generalized and accurate diffusion tensor imaging.

Diffusion tensor imaging (DTI) is a prevalent magnetic resonance imaging (MRI) technique, widely used in clinical and neuroscience research. However, the reliability of DTI is affected by the low signal-to-noise ratio inherent in diffusion-weighted (DW) images. Deep learning (DL) has shown promise in improving the quality of DTI, but its limited generalization to variable acquisition schemes hinders practical applications. This study aims to develop a generalized, accurate, and efficient DL-based DTI method. By leveraging the representation of voxel-wise diffusion MRI (dMRI) signals on the sphere using spherical harmonics (SH), we propose a novel approach that utilizes SH coefficient maps as input to a network for predicting the diffusion tensor (DT) field, enabling improved generalization. Extensive experiments were conducted on simulated and in-vivo datasets, covering various DTI application scenarios. The results demonstrate that the proposed SH-DTI method achieves advanced performance in both quantitative and qualitative analyses of DTI. Moreover, it exhibits remarkable generalization capabilities across different acquisition schemes, centers, and scanners, ensuring its broad applicability in diverse settings.

Can cerebellar theta-burst stimulation improve balance function and gait in stroke patients? A randomized controlled trial.

BACKGROUND: The cerebellum is a key structure involved in balance and motor control, and has become a new stimulation target in brain regulation technology. Interference theta-burst simulation (iTBS) is a novel simulation mode of repetitive transcranial magnetic simulation. However, the impact of cerebellar iTBS on balance function and gait in stroke patients is still unknown. AIM: The aim of this study was to determine whether cerebellar iTBS can improve function, particularly balance and gait, in patients with post-stroke hemiplegia. DESIGN: This study is a randomized, double-blind, sham controlled clinical trial. SETTING: The study was carried out at the Department of Rehabilitation Medicine in a general hospital. POPULATION: Patients with stroke with first unilateral lesions were enrolled in the study. METHODS: Thirty-six patients were randomly assigned to the cerebellar iTBS group or sham stimulation group. The cerebellar iTBS or pseudo stimulation site is the ipsilateral cerebellum on the paralyzed side, which is completed just before daily physical therapy. The study was conducted five times a week for two consecutive weeks. All patients were assessed before the intervention (T0) and at the end of 2 weeks of treatment (T1), respectively. The primary outcome was the Berg Balance Scale (BBS), while secondary outcome measures included the Fugl Meyer Lower Limb Assessment Scale (FMA-LE), timed up and go (TUG), Barthel Index (BI), and gait analysis. RESULTS: After 2 weeks of intervention, the BBS, FMA-LE, TUG, and BI score in both the iTBS group and the sham group were significantly improved compared to the baseline (all P<0.05). Also, there was a significant gait parameter improvement including the cadence, stride length, velocity, step length compared to the baseline (P<0.05) in the iTBS group, but only significant improvement in cadence was identified in the sham group (P<0.05). Intergroup comparison showed that the BBS (P<0.001), FMA-LE (P<0.001), and BI (P=0.002) in the iTBS group were significantly higher than those in the sham group, and the TUG in the iTBS was significantly lower than that in the sham group (P=0.002). In addition, there were significant differences in cadence (P=0.029), strip length (P=0.046), gain velocity (P=0.002), and step length of affected lower limb (P=0.024) between the iTBS group and the sham iTBS group. CONCLUSIONS: Physical therapy is able to improve the functional recovery in hemiplegic patients after stroke, but the cerebellar iTBS can facilitate and accelerate the recovery, particularly the balance function and gait. Cerebellar iTBS could be an efficient and facilitative treatment for patients with stroke. CLINICAL REHABILITATION IMPACT: Cerebellar iTBS provides a convenient and efficient treatment modality for functional recovery of patients with stroke, especially balance function and gait.

A Case of an 82-Year-Old Man with a Spinal Extradural Malignant Ossifying Fibromyxoid Tumor.

BACKGROUND Ossifying fibromyxoid tumor (OFMT) is a rare mesenchymal tumor predominantly involving the subcutaneous tissues or skeletal muscles in the proximal extremities, typically in middle-aged men. OFMT in the spine is extremely rare, with only 3 previously reported cases in the literature. CASE REPORT Here, we present a rare case of an 82-year-old man presenting with paresthesia of both arms and weakness of both legs, who underwent magnetic resonance imaging (MRI) of the spine, which showed an aggressive extradural tumor. Following surgical debulking, histology examination revealed a tumor of stromal origin with myxoid and ossifying components and pleomorphic features. Overall findings were suggestive of a malignant OFMT. The patient underwent postoperative adjuvant radiotherapy. However, the first follow-up MRI study at 8 months showed residual tumor, which also demonstrated avid tracer uptake on technetium-99m scintigraphy and PET-CT scans. The second MRI follow-up about 9 months later showed several metastatic foci along the craniospinal axis. Despite subsequent resection of the spinal metastasis, the patient eventually died of sepsis about 21 months after the initial tumor diagnosis. CONCLUSIONS We presented a case of extradural spinal malignant OFMT and highlighted the difficulty distinguishing this rare primary tumor from spinal metastases. In this case, MRI signal intensities and identifying intratumoral bone formation, combined with histopathology following surgical resection, confirmed the diagnosis. This case has also shown the importance of follow-up by a multidisciplinary team to monitor for the recurrence of primary OFMT.

Identifying Immune-Specific Subtypes of Adrenocortical Carcinoma Based on Immunogenomic Profiling.

BACKGROUND: The tumor immune microenvironment (TIME) of adrenocortical carcinoma (ACC) is heterogeneous. However, a classification of ACC based on the TIME remains unexplored. METHODS: We hierarchically clustered ACC based on the enrichment levels of twenty-three immune signatures to identify its immune-specific subtypes. Furthermore, we comprehensively compared the clinical and molecular profiles between the subtypes. RESULTS: We identified two immune-specific subtypes of ACC: Immunity-H and Immunity-L, which had high and low immune signature scores, respectively. We demonstrated that this subtyping method was stable and reproducible by analyzing five different ACC cohorts. Compared with Immunity-H, Immunity-L had lower levels of immune cell infiltration, worse overall and disease-free survival prognosis, and higher tumor stemness, genomic instability, proliferation potential, and intratumor heterogeneity. Furthermore, the ACC driver gene CTNNB1 was more frequently mutated in Immunity-L than in Immunity-H. Several proteins, such as mTOR, ERCC1, Akt, ACC1, Cyclin_E1, ß-catenin, FASN, and GAPDH, were more highly expressed in Immunity-L than in Immunity-H. In contrast, p53, Syk, Lck, PREX1, and MAPK were more highly expressed in Immunity-H. Pathway and gene ontology analysis showed that the immune, stromal, and apoptosis pathways were highly enriched in Immunity-H, while the cell cycle, steroid biosynthesis, and DNA damage repair pathways were highly enriched in Immunity-L. CONCLUSIONS: ACC can be classified into two stable immune-related subtypes, which have significantly different antitumor responses, molecular characteristics, and clinical outcomes. This subtyping may provide clinical implications for prognostic and immunotherapeutic stratification of ACC.

Research status and prospects of acupuncture for autism spectrum disorders.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder and has a predilection for children. Its symptoms, such as lifelong social communication deficits and repetitive sensory-motor behaviors, put a huge burden on the patient's family and society. Currently, there is no cure for ASD, and some medications that can improve its symptoms are often accompanied by adverse effects. Among many complementary and alternative medicine (CAM) therapies, acupuncture has shown promising application potential, but after years of practice, it has not been recognized as the preferred CAM therapy for ASD. Therefore, we analyzed and discussed the clinical study reports of acupuncture in the treatment of ASD in the past 15 years from the aspects of study subjects, group setting, intervention modalities, acupoint selection, outcome evaluation, and safety. The data accumulated at present are not sufficient to support the clinical effectiveness of acupuncture in ASD and to justify its use in clinical practice. They provide, however, initial evidence of possible effectiveness and encourage further investigation in order to reach firm conclusions. Based on a comprehensive analysis, we believed that following the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) and Consolidated Standards of Reporting Trials (CONSORT), screening the optimal combination of acupoints applying a rigorous scientific study design, and performing the related functional experiments may be the effective way to convincingly test the hypothesis that acupuncture may be beneficial in ASD patients. The significance of this review is to provide a reference for researchers to carry out high-quality clinical trials of acupuncture in the treatment of ASD from the perspective of the combination of modern medicine and traditional Chinese medicine.

Cascade of Denoising and Mapping Neural Networks for MRI R2* Relaxometry of Iron-Loaded Liver.

MRI of effective transverse relaxation rate (R2*) measurement is a reliable method for liver iron concentration quantification. However, R2* mapping can be degraded by noise, especially in the case of iron overload. This study aimed to develop a deep learning method for MRI R2* relaxometry of an iron-loaded liver using a two-stage cascaded neural network. The proposed method, named CadamNet, combines two convolutional neural networks separately designed for image denoising and parameter mapping into a cascade framework, and the physics-based R2* decay model was incorporated in training the mapping network to enforce data consistency further. CadamNet was trained using simulated liver data with Rician noise, which was constructed from clinical liver data. The performance of CadamNet was quantitatively evaluated on simulated data with varying noise levels as well as clinical liver data and compared with the single-stage parameter mapping network (MappingNet) and two conventional model-based R2* mapping methods. CadamNet consistently achieved high-quality R2* maps and outperformed MappingNet at varying noise levels. Compared with conventional R2* mapping methods, CadamNet yielded R2* maps with lower errors, higher quality, and substantially increased efficiency. In conclusion, the proposed CadamNet enables accurate and efficient iron-loaded liver R2* mapping, especially in the presence of severe noise.

Quorum sensing system effectively enhances DegU-mediated degradation of pyrethroids by Bacillus subtilis.

The contamination of the natural environment is a growing concern that threatens all life forms, including microorganisms. Bacteria protect themselves by initiating quorum sensing (QS), a bacterial cell-cell communication, to generate adaptive responses to these pollutants. Bacillus subtilis has a typical QS ComQXPA system that regulates the phosphorylation of the transcription factor DegU (DegU-P), and thus can mediate the expression of various downstream genes under different stress conditions. Herein, we found that cesB, a gene of Bacillus subtilis 168, plays a key role in pyrethroid degradation, and cesB-mediated degradation could be enhanced by coordinating with the ComX communication system. Using ß-cypermethrin (ß-CP) as a paradigm, we demonstrated that DegU-P increased upon exposure to ß-CP, thus facilitating ß-CP degradation by binding to the upstream regulatory regions of cesB, leading to the activation of the expression of cesB. Further, we showed that the expression of different levels of phosphorylated DegU in a degU deletion strain resulted in varying degrees of ß-CP degradation efficiency, with phosphorylated DegUH12L achieving 78.39% degradation efficiency on the first day, surpassing the 56.27% degradation efficiency in the wild type strain. Consequently, based on the conserved regulatory mechanism of ComQXPA system, we propose that DegU-P-dependent regulation serves as a conserved defense mechanism owing to its ability to fine-tune the expression of genes involved in the degradation of pollutants upon exposure to different pesticides.

Gene set enrichment analysis identifies immune subtypes of kidney renal clear cell carcinoma with significantly different molecular and clinical properties.

Background: Kidney renal clear cell carcinoma (KIRC) is the most prevalent renal malignancy, marked by a high abundance of tumor-infiltrating lymphocytes (TILs) and an unfavorable prognosis upon metastasis. Numerous studies have demonstrated that KIRC possesses a tumor microenvironment that is highly heterogeneous, and this is associated with significant variations in the effectiveness of most first-line drugs administered to KIRC patients. Therefore, it is crucial to classify KIRC based on the tumor microenvironment, although these subtyping techniques are still inadequate. Methods: By applying gene set enrichment scores of 28 immune signatures, we conducted a hierarchical clustering of KIRC and determined its immune subtypes. In addition, we conducted a comprehensive exploration of the molecular and clinical features of these subtypes, including survival prognosis, proliferation, stemness, angiogenesis, tumor microenvironment, genome instability, intratumor heterogeneity, and pathway enrichment. Results: Through cluster analysis, two immune subtypes of KIRC were identified and termed Immunity-High (Immunity-H) and Immunity-Low (Immunity-L). This clustering outcome was consistent in four independent KIRC cohorts. The subtype Immunity-H exhibited elevated levels of TILs, tumor aneuploidy, homologous recombination deficiency, stemness, and proliferation potential, along with a poorer prognosis for survival. Despite this, the Immunity-L subtype demonstrated elevated intratumor heterogeneity and a stronger angiogenesis signature in contrast to Immunity-H. According to the results of pathway enrichment analysis, the Immunity-H subtype was found to be highly enriched in immunological, oncogenic, and metabolic pathways, whereas the Immunity-L subtype was highly enriched in angiogenic, neuroactive ligand-receptor interaction, and PPAR pathways. Conclusions: Based on the enrichment of immune signatures in the tumor microenvironment, KIRC can be categorized into two immune subtypes. The two subtypes demonstrate considerably distinct molecular and clinical features. In KIRC, an increase in immune infiltration is linked to a poor prognosis. Patients with Immunity-H KIRC may exhibit active responses to PPAR and immune checkpoint inhibitors, whereas patients with Immunity-L may manifest favorable responses to anti-angiogenic agents and immune checkpoint inhibitors. The immunological classification provides molecular insights into KIRC immunity, as well as clinical implications for the management of this disease.

Efficacy of Tai Chi on lower limb function of Parkinson's disease patients: A systematic review and meta-analysis.

Background: At present, the effect of Tai Chi (TC) on lower limb function in patients with Parkinson's disease (PD) is controversial. Therefore, we conducted a meta-analysis on the influence of TC on lower limb function in PD patients. Methods: According to the PRISMA guidelines, seven databases were searched. Randomized controlled trials (RCTS) were selected and screened according to inclusion and exclusion criteria. We assessed the quality of the studies using the Cochrane Risk of Bias tool and then extracted the characteristics of the included studies. The random effect model was adopted, and heterogeneity was measured by I 2 statistic. Results: A total of 441 articles were screened, and 10 high-quality RCTs were with a total of 532 patients with PD met Our inclusion criteria. Meta-analysis showed that compared To control groups TC improved several outcomes. TC significantly improved motor function (SMD = -0.70; 95% CI = -0.95, -0.45; p < 0.001; I 2 = 35%), although The results were not statistically significant for The subgroup analysis of TC duration (SMD = -0.70; 95% CI = -0.95, -0.45; p = 0.88; I 2 = 0%;). TC significantly improved balance function (SMD = 0.89; 95% CI = 0.51, 1.27; p < 0.001; I 2 = 54%), functional walking capacity (SMD = -1.24; 95% CI = -2.40, -0.09; p = 0.04; I 2 = 95%), and gait velocity (SMD = 0.48; 95% CI = -0.02, 0.94; p = 0.04; I 2 = 78%), But Did Not improve endurance (SMD = 0.31; 95% CI = -0.12, 0.75; p = 0.16; I 2 = 0%), step length (SMD = 0.01; 95% CI = -0.34, 0.37; p = 0.94; I 2 = 29%), and cadence (SMD = 0.06; 95% CI = -0.25, 0.36; p = 0.70; I 2 = 0%). Conclusion: TC has beneficial effects on motor function, balance function, functional walking ability, and gait velocity, but does not improve walking endurance, stride length, and cadence.

Molecular Mechanisms of Tebuconazole Affecting the Social Behavior and Reproduction of Zebrafish.

The aim of this study was to explore the underlying mechanism of adverse effects caused by tebuconazole (TEB) on the reproduction of aquatic organisms In the present study, in order to explore the effects of TEB on reproduction, four-month-old zebrafish were exposed to TEB (0, DMSO, 0.4 mg/L, 0.8 mg/L, and 1.6 mg/L) for 21 days. After exposure, the accumulations of TEB in gonads were observed and the cumulative egg production was evidently decreased. The decline of fertilization rate in F1 embryos was also observed. Then the changes in sperm motility and histomorphology of gonads were discovered, evaluating that TEB had adverse effects on gonadal development. Additionally, we also found the alternations of social behavior, 17ß-estradiol (E2) level, and testosterone (T) level. Furthermore, the expression levels of genes involved in the hypothalamic-pituitary-gonadal (HPG) axis and social behavior were remarkably altered. Taken together, it could be concluded that TEB affected the egg production and fertilization rate by interfering with gonadal development, sex hormone secretion, and social behavior, which were eventually attributed to the disruption of the expressions of genes associated with the HPG axis and social behavior. This study provides a new perspective to understanding the mechanism of TEB-induced reproductive toxicity.