Osr2 functions as a biomechanical checkpoint to aggravate CD8+ T cell exhaustion in tumor.

Alterations in extracellular matrix (ECM) architecture and stiffness represent hallmarks of cancer. Whether the biomechanical property of ECM impacts the functionality of tumor-reactive CD8+ T cells remains largely unknown. Here, we reveal that the transcription factor (TF) Osr2 integrates biomechanical signaling and facilitates the terminal exhaustion of tumor-reactive CD8+ T cells. Osr2 expression is selectively induced in the terminally exhausted tumor-specific CD8+ T cell subset by coupled T cell receptor (TCR) signaling and biomechanical stress mediated by the Piezo1/calcium/CREB axis. Consistently, depletion of Osr2 alleviates the exhaustion of tumor-specific CD8+ T cells or CAR-T cells, whereas forced Osr2 expression aggravates their exhaustion in solid tumor models. Mechanistically, Osr2 recruits HDAC3 to rewire the epigenetic program for suppressing cytotoxic gene expression and promoting CD8+ T cell exhaustion. Thus, our results unravel Osr2 functions as a biomechanical checkpoint to exacerbate CD8+ T cell exhaustion and could be targeted to potentiate cancer immunotherapy.

Spatiotemporal ATF3 Expression Determines VSMC Fate in Abdominal Aortic Aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a catastrophic disease with little effective therapy, likely due to the limited understanding of the mechanisms underlying AAA development and progression. ATF3 (activating transcription factor 3) has been increasingly recognized as a key regulator of cardiovascular diseases. However, the role of ATF3 in AAA development and progression remains elusive. METHODS: Genome-wide RNA sequencing analysis was performed on the aorta isolated from saline or Ang II (angiotensin II)-induced AAA mice, and ATF3 was identified as the potential key gene for AAA development. To examine the role of ATF3 in AAA development, vascular smooth muscle cell-specific ATF3 knockdown or overexpressed mice by recombinant adeno-associated virus serotype 9 vectors carrying ATF3, or shRNA-ATF3 with SM22α (smooth muscle protein 22-α) promoter were used in Ang II-induced AAA mice. In human and murine vascular smooth muscle cells, gain or loss of function experiments were performed to investigate the role of ATF3 in vascular smooth muscle cell proliferation and apoptosis. RESULTS: In both Ang II-induced AAA mice and patients with AAA, the expression of ATF3 was reduced in aneurysm tissues but increased in aortic lesion tissues. The deficiency of ATF3 in vascular smooth muscle cell promoted AAA formation in Ang II-induced AAA mice. PDGFRB (platelet-derived growth factor receptor ß) was identified as the target of ATF3, which mediated vascular smooth muscle cell proliferation in response to TNF-alpha (tumor necrosis factor-α) at the early stage of AAA. ATF3 suppressed the mitochondria-dependent apoptosis at the advanced stage by upregulating its direct target BCL2. Our chromatin immunoprecipitation results also demonstrated that the recruitment of NFκB1 and P300/BAF/H3K27ac complex to the ATF3 promoter induces ATF3 transcription via enhancer activation. NFKB1 inhibitor (andrographolide) inhibits the expression of ATF3 by blocking the recruiters NFKB1 and ATF3-enhancer to the ATF3-promoter region, ultimately leading to AAA development. CONCLUSIONS: Our results demonstrate a previously unrecognized role of ATF3 in AAA development and progression, and ATF3 may serve as a novel therapeutic and prognostic marker for AAA.

Altered brain function in classical trigeminal neuralgia patients: ALFF, ReHo, and DC static- and dynamic-frequency study.

The present study aimed to clarify the brain function of classical trigeminal neuralgia (CTN) by analyzing 77 CTN patients and age- and gender-matched 73 healthy controls (HCs) based on three frequency bands of the static and dynamic amplitude of low-frequency fluctuation, regional homogeneity, and degree centrality (sALFF, sReHo, sDC, dALFF, dReHo, and dDC). Compared to HCs, the number of altered brain regions was different in three frequency bands, and the classical frequency band was most followed by slow-4 in CTN patients. Cerrelellum_8_L (sReHo), Cerrelellum_8_R (sDC), Calcarine_R (sDC), and Caudate_R (sDC) were found only in classical frequency band, while Precuneus_L (sALFF) and Frontal_Inf_Tri_L (sReHo) were found only in slow-4 frequency band. Except for the above six brain regions, the others overlapped in the classical and slow-4 frequency bands. CTN seriously affects the mental health of patients, and some different brain regions are correlated with clinical parameters. The static and dynamic indicators of brain function were complementary in CTN patients, and the changing brain regions showed frequency specificity. Compared to slow-5 frequency band, slow-4 is more consistent with the classical frequency band, which could be valuable in exploring the pathophysiology of CTN.

Dental data challenge the ubiquitous presence of Homo in the Cradle of Humankind.

The origins of Homo, as well as the diversity and biogeographic distribution of early Homo species, remain critical outstanding issues in paleoanthropology. Debates about the recognition of early Homo, first appearance dates, and taxonomic diversity within Homo are particularly important for determining the role that southern African taxa may have played in the origins of the genus. The correct identification of Homo remains also has implications for reconstructing phylogenetic relationships between species of Australopithecus and Paranthropus, and the links between early Homo species and Homo erectus. We use microcomputed tomography and landmark-free deformation-based three-dimensional geometric morphometrics to extract taxonomically informative data from the internal structure of postcanine teeth attributed to Early Pleistocene Homo in the southern African hominin-bearing sites of Sterkfontein, Swartkrans, Drimolen, and Kromdraai B. Our results indicate that, from our sample of 23 specimens, only 4 are unambiguously attributed to Homo, 3 of them coming from Swartkrans member 1 (SK 27, SK 847, and SKX 21204) and 1 from Sterkfontein (Sts 9). Three other specimens from Sterkfontein (StW 80 and 81, SE 1508, and StW 669) approximate the Homo condition in terms of overall enamel-dentine junction shape, but retain Australopithecus-like dental traits, and their generic status remains unclear. The other specimens, including SK 15, present a dominant australopith dental signature. In light of these results, previous dietary and ecological interpretations can be reevaluated, showing that the geochemical signal of one tooth from Kromdraai (KB 5223) and two from Swartkrans (SK 96 and SKX 268) is consistent with that of australopiths.

S-Nitrosylation of the histone deacetylase HDA19 stimulates its activity to enhance plant stress tolerance in Arabidopsis.

Arabidopsis histone deacetylase HDA19 is required for gene expression programs of a large spectrum of plant developmental and stress-responsive pathways. How this enzyme senses cellular environment to control its activity remains unclear. In this work, we show that HDA19 is post-translationally modified by S-nitrosylation at 4 Cysteine (Cys) residues. HDA19 S-nitrosylation depends on the cellular nitric oxide level, which is enhanced under oxidative stress. We find that HDA19 is required for cellular redox homeostasis and plant tolerance to oxidative stress, which in turn stimulates its nuclear enrichment, S-nitrosylation and epigenetic functions including binding to genomic targets, histone deacetylation and gene repression. The Cys137 of the protein is involved in basal and stress-induced S-nitrosylation, and is required for HDA19 functions in developmental, stress-responsive and epigenetic controls. Together, these results indicate that S-nitrosylation regulates HDA19 activity and is a mechanism of redox-sensing for chromatin regulation of plant tolerance to stress.

Complete mitochondrial genome of Melia azedarach L., reveals two conformations generated by the repeat sequence mediated recombination.

Melia azedarach is a species of enormous value of pharmaceutical industries. Although the chloroplast genome of M. azedarach has been explored, the information of mitochondrial genome (Mt genome) remains surprisingly limited. In this study, we used a hybrid assembly strategy of BGI short-reads and Nanopore long-reads to assemble the Mt genome of M. azedarach. The Mt genome of M. azedarach is characterized by two circular chromosomes with 350,142 bp and 290,387 bp in length, respectively, which encodes 35 protein-coding genes (PCGs), 23 tRNA genes, and 3 rRNA genes. A pair of direct repeats (R1 and R2) were associated with genome recombination, resulting in two conformations based on the Sanger sequencing and Oxford Nanopore sequencing. Comparative analysis identified 19 homologous fragments between Mt and chloroplast genome, with the longest fragment of 12,142 bp. The phylogenetic analysis based on PCGs were consist with the latest classification of the Angiosperm Phylogeny Group. Notably, a total of 356 potential RNA editing sites were predicted based on 35 PCGs, and the editing events lead to the formation of the stop codon in the rps10 gene and the start codons in the nad4L and atp9 genes, which were verified by PCR amplification and Sanger sequencing. Taken together, the exploration of M. azedarach gap-free Mt genome provides a new insight into the evolution research and complex mitogenome architecture.

PCDHGB7 hypermethylation-based Cervical cancer Methylation (CerMe) detection for the triage of high-risk human papillomavirus-positive women: a prospective cohort study.

BACKGROUND: Implementation of high-risk human papillomavirus (hrHPV) screening has greatly reduced the incidence and mortality of cervical cancer. However, a triage strategy that is effective, noninvasive, and independent from the subjective interpretation of pathologists is urgently required to decrease unnecessary colposcopy referrals in hrHPV-positive women. METHODS: A total of 3251 hrHPV-positive women aged 30-82 years (median = 41 years) from International Peace Maternity and Child Health Hospital were included in the training set (n = 2116) and the validation set (n = 1135) to establish Cervical cancer Methylation (CerMe) detection. The performance of CerMe as a triage for hrHPV-positive women was evaluated. RESULTS: CerMe detection efficiently distinguished cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) from cervical intraepithelial neoplasia grade 1 or normal (CIN1 -) women with excellent sensitivity of 82.4% (95% CI = 72.6 ~ 89.8%) and specificity of 91.1% (95% CI = 89.2 ~ 92.7%). Importantly, CerMe showed improved specificity (92.1% vs. 74.9%) in other 12 hrHPV type-positive women as well as superior sensitivity (80.8% vs. 61.5%) and specificity (88.9% vs. 75.3%) in HPV16/18 type-positive women compared with cytology testing. CerMe performed well in the triage of hrHPV-positive women with ASC-US (sensitivity = 74.4%, specificity = 87.5%) or LSIL cytology (sensitivity = 84.4%, specificity = 83.9%). CONCLUSIONS: PCDHGB7 hypermethylation-based CerMe detection can be used as a triage strategy for hrHPV-positive women to reduce unnecessary over-referrals. TRIAL REGISTRATION: ChiCTR2100048972. Registered on 19 July 2021.

Background-Free Imaging of Food Freshness Using Curcumin-Functionalized Upconversion Reversible Hydrogel Patch.

Functionalized upconversion nanomaterials can overcome the drawbacks faced of strong background interference, photodamage, and spectral overlap by conventional optical labeling. Here, curcumin-functionalized upconversion hydrogel patch is designed with background-free and reversible for food freshness monitoring by ultra-sensitive response to biogenic amines. By loading the probes onto hydrogel patch, utilizing the good ductility to solve the problem of non-smooth surface coverage, thus accurately capturing biogenic amines. The presence of biogenic amines leads to the conversion of the diketone group on the probe to enolate ions, which triggers fluorescence resonance energy transfer (FRET) and ultimately causes the upconverted fluorescence to gradually change from green to red. The probe exhibits good detection capability for biogenic amines with a low limit of detection (LOD) of 2.73 µm. Interestingly, the patch can be restored to its initial state after water rinsing, realizing reversible detection of biogenic amines. Additionally, combining the color recognition system of smartphone can convert the imaging signal into a data signal to achieve quantitative analysis and show a reliable assessment comparable to the results of high performance liquid chromatography (HPLC). This study demonstrates the practical applicability in real-time monitoring of freshness, suggests great potential in developing optical nano-sensing strategy to ensure food safety.

Combined transcriptome and metabolome analysis identifies triterpenoid-induced defense responses in Myzus persicae Sülzer-infested peach.

Piercing/sucking insects such as green peach aphid (GPA) (Myzus persicae) cause direct damage by obtaining phloem nutrients and indirect damage by spreading plant viruses. To investigate the response of peach trees (Prunus persica) to aphids, the leaf transcriptome and metabolome of two genotypes with different sensitivities to GPA were studied. The gene expression of aphid-susceptible plants infested with aphids was similar to that of control plants, whereas the gene expression of aphid-resistant plants infested with aphids showed strong induced changes in gene expression compared with control plants. Furthermore, gene transcripts in defense-related pathways, including plant-pathogen interaction, MAPK signaling, and several metabolic pathways, were strongly enriched upon aphid infestation. Untargeted secondary metabolite profiling confirmed that aphid infestation induced larger changes in aphid-resistant than in aphid-susceptible peaches. Consistent with transcriptomic alterations, nine triterpenoids showed highly significant GPA-induced accumulation in aphid-resistant peaches, whereas triterpenoid abundance remained predominantly unchanged or undetected in aphid-susceptible peaches. Furthermore, some types of transcription factors (including WRKYs, ERFs, and NACs) were strongly induced upon GPA infestation in aphid-resistant, but not in aphid-susceptible peaches. These results suggested that the accumulation of specialized triterpenoids and the corresponding pathway transcripts may play a key role in peach GPA resistance.

Constitutively expressed small heat shock protein LsHsp21.5 not only enhances heat tolerance but also helps to maintain reproduction in female Laodelphax striatellus.

Coping with stressful conditions and maintaining reproduction are two key biological processes that affect insect population dynamics. Small heat shock proteins (sHSPs) are involved in the stress response and the development of insects. The sHsp gene Laodelphax striatellus (Hemiptera: Delphacidae) sHsp 21.5 (LsHsp21.5) showed constitutive, stage- and organ-specific expression in L. striatellus, a pest that damages cultivated rice in east Asia. The expression of LsHsp21.5 was highest in the ovary, with 43.60, 12.99 and 1.45 time higher expression here than in the head, gut and female fat bodies, respectively. The expression of this gene was weakly affected by heat or cold shock. The gene provided in vitro protection against heat damage to malate dehydrogenase and in vivo protection against heat stress in Escherichia coli (Enterobacteriales: Enterobacteriaceae) BL21(DE3) and L. striatellus. Moreover, L. striatellus reproduction decreased by 1.85 times when the expression of LsHsp21.5 was inhibited by RNA interference. The expression of some genes related to reproduction, such as the homologous gene of chorion protein, also declined. These results suggest that LsHsp21.5 expression not only protects other proteins against stress but also helps maintain the stable expression of some reproduction-related genes under non-stressful conditions, with impacts on L. striatellus fecundity.

Development and Validation of a Fusion Model Based on Carotid Plaques and White Matter Lesion Burden Imaging Characteristics to Evaluate Ischemic Stroke Severity in Symptomatic Patients.

BACKGROUND: The diagnostic value of carotid plaque characteristics based on higher-resolution vessel wall MRI (HRVW-MRI) combined with white matter lesion (WML) burden for the risk of ischemic stroke is unclear. PURPOSE: To combine carotid plaque features and WML burden to construct a hybrid model for evaluating ischemic stroke severity and prognosis in patients with symptomatic carotid artery stenosis. STUDY TYPE: Retrospective. SUBJECTS: One hundred and ninty-three patients with least one confirmed carotid atherosclerotic stenosis ≥30% and cerebrovascular symptoms within the last 2 weeks (136 in the training cohort and 57 in the test cohort). FIELD STRENGTH/SEQUENCE: 3.0T, T2-weighted fluid attenuated inversion recovery (T2-FLAIR) and diffusion-weighted imaging (DWI); HRVW-MRI: 3D T1-weighted variable flip angle fast spin-echo sequences (VISTA), T2-weighted VISTA, simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP), and contrast-enhanced T1-VISTA. ASSESSMENT: The following features of the plaques or vessel wall were assessed by three MRI readers independently: calcification (CA), intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), ulceration, plaque enhancement (PE), maximum vessel diameter (Max VD), maximum wall thickness (Max WT), total vessel area (TVA), lumen area (LA), plaque volume, and lumen stenosis. WMLs were graded visually and categorized as absent-to-mild WMLs (Fazekas score 0-2) or moderate-severe WMLs (Fazekas score 3-6). WML volumes were quantified using a semiautomated volumetric analysis program. Modified Rankin scores (mRS) were assessed at 90 days, following an outpatient interview, or by telephone. STATISTICAL TESTS: LASSO-logistic regression analysis was performed to construct a model. The performance of the model was evaluated using receiver operating characteristic (ROC) curve analyses, calibration curves, decision curve analyses, and clinical imaging curves. Conditional logistic regression analysis was used to explore the associations between the hybrid model-derived score and the modified Rankin Scale (mRS) score at 90 days. RESULTS: The model was constructed using five selected features, including IPH, plaque enhancement, ulceration, NWI, and total Fazekas score in deep WMLs (DWMLs). The hybrid model yielded an area under the curve of 0.92 (95% confidence interval [CI] 0.87-0.97) in the training cohort and 0.88 (0.80-0.96) in the test cohort. Furthermore, the hybrid model-derived score (odds ratio = 1.28; 95% CI 1.06-1.53) was independently associated with the mRS score 90 days after stroke. DATA CONCLUSIONS: The hybrid model constructed using MRI plaque characteristics and WML burden has potential to be an effective noninvasive method of assessing ischemic stroke severity. The model-derived score has promising utility in judging neurological function recovery. TECHNICAL EFFICACY: Stage 2.

Thin Liquid Film View and Shear Stress During the Sliding of Air Bubbles on Tilted Plates.

The challenge when studying the impact and sliding of free-rising air bubbles on tilted surfaces is an experimental limitation in obtaining the film thickness of thin liquid film (TLF) during the bubbles' sliding on tilted surfaces. In this work, spatiotemporal evolution in the film thickness of the moving TLF between a sliding air bubble and a tilted plate was monitored by using a two-wavelength synchronized reflection interferometry microscopy (SRIM) technique. The evolution of the film thickness was directly determined from a timed series of monochromatic interference fringes recorded simultaneously at two different wavelengths. From the film thickness profile, a shear stress map at a given time was determined at different bubble sizes and inclination angles. Results showed that the film thickness of TLFs during the bubbles' sliding on tilted surfaces was in the range of 300-1200 nm, depending on bubble size and tilting angles. Sliding of air bubbles on tilted plates over a thin gap with a few hundred nanometers thickness yielded shear stress in the order of 10-50 Pa. Both the larger bubble size and higher tilting angles yielded a higher shear stress. Experimental results were quantitatively compared to numerical results obtained using the Reynolds lubrication theory. A good match between the two results was achieved. Numerical results suggested that a maximum shear stress exerted on a tilted plate occurred at a 25° tilting angle. This is the first time that the spatiotemporal evolution of TLF during bubbles' sliding on tilted surfaces has been achieved, and the shear stress exerted on the tilted surface has been directly determined.

Biobased Tannic Acid-Chitosan Composite Membranes as Reusable Adsorbents for Effective Enrichment of Phosphopeptides.

High-performance reusable materials from renewable resources are rare and urgently required in bioseparation. Herein, a series of tannic acid-chitosan composite membranes for the enrichment of phosphopeptides were fabricated by the freeze casting method. First, a tannic acid-chitosan composite membrane was acquired via the multiple hydrogen bonds between tannic acid and chitosan, which had a long-range aligned three-dimensional microstructure. Second, a covalent-hydrogen bond hybrid composite was also fabricated, with stable and aligned honeycomb-like microstructures that formed by the synergy of covalence and hydrogen bonding. Besides, a ternary composite membrane was "one-pot" synthesized by the copolymerization of tannic acid, chitosan, and Ti4+ ions, indicating the feasibility of involving metal ions in the composition of the polymer skeleton in place of additional modification steps. The as-prepared chitosan composite membranes exhibited excellent performance in the enrichment of phosphopeptides from ß-casein tryptic digest and human serum. Benefitting from the long-range aligned honeycomb-like structure coordinated by hydrogen bonds and covalent bonds, and a large number of pyrogallol functional groups provided by tannic acid, the covalent-hydrogen bond hybrid membrane showed excellent reusability and could be reused up to 16 times in phosphopeptide enrichment, as far as we know, which is the best reported result to date.

Relevance of combined influence of nutritional and inflammatory status on non-alcoholic fatty liver disease and advanced fibrosis: A mediation analysis of lipid biomarkers.

BACKGROUND AND AIM: This study aimed to investigate the relationship between advanced lung cancer inflammation index (ALI) and non-alcoholic fatty liver disease (NAFLD) and advanced liver fibrosis (AF). METHODS: A total of 5642 individuals from the National Health and Nutrition Examination Survey (NHANES) between 2017 and 2020 were examined. Limited cubic spline regression model, and weighted logistic regression were employed to determine if ALI levels were related to the prevalence of NAFLD and AF. Additionally, a mediating analysis was conducted to investigate the role of lipid biomarkers, such as total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), in the effects of ALI on the prevalence of NAFLD and AF. RESULTS: After adjusting for potential confounders, a significant positive association was found between ALI with NAFLD and AF prevalence. Compared with those in ALI Tertile 1, participants in Tertile 3 had higher odds of NAFLD prevalence (odds ratio [OR]: 3.16; 95% confidence interval [CI]: 2.52-3.97) and AF (OR: 3.17; 95% CI: 2.30-4.36). Participants in both Tertile 2 and Tertile 3 had lower odds of developing AF (P for trend = 0.005). Moreover, we discovered a nonlinear association between ALI and NAFLD. An inflection point of 74.25 for NAFLD was identified through a two-segment linear regression model. Moreover, TC and HDL-C levels mediated the association between ALI and NAFLD by 10.2% and 4.2%, respectively (both P < 0.001). CONCLUSION: Our findings suggest that higher ALI levels are positively associated with an increased prevalence of NAFLD and AF, partly mediated by lipid biomarkers.

The MYB transcription factor PpMYB5 regulates Pp4CL1/Pp4CL2 expression to promote lignin biosynthesis of fruit russeting in the flat nectarine.

KEY MESSAGE: Transcription factor PpMYB5 promotes lignin synthesis by directly binding to the Pp4CL1/Pp4CL2 promoter and affecting their expression, which may be related to nectarine russeting formation. Nectarine russeting is usually considered to be a non-invasive physiological disease that usually occurs on late-maturing cultivars and seriously affects their appearance quality and commercial value. The cause of nectarine fruit rust is currently unknown. In this study, we compared two flat nectarine cultivars, 'zhongyoupanweidi' (HD; russeting-free cultivar) and 'zhongyoupanweihou' (TH; russeting-prone cultivar), with respect to nectarine russeting by means of microscopy, transcriptomics, and hormone analysis. Compared to HD fruits, TH fruits had a broken cuticle, missing wax layer, and heavy lignin deposition. RNA sequencing (RNA-seq) revealed significant alternations in the expression of genes related to lignin synthesis. Moreover, structure genes Pp4CL1 and Pp4CL2, MYB transcription factor (TF) gene PpMYB5 were identified through weighted gene co-expression network analysis (WGCNA). Molecular experiments and transgenic evidence suggested that PpMYB5 regulates Pp4CL1/Pp4CL2 expression to promote lignin synthesis. Overall, in addition to providing new insights into the formation of mechanisms for nectarine russeting, our study also establishes a foundation for nectarine russeting prevention.

Application research on the diagnosis of classic trigeminal neuralgia based on VB-Net technology and radiomics.

BACKGROUND: This study aims to utilize the deep learning method of VB-Net to locate and segment the trigeminal nerve, and employ radiomics methods to distinguish between CTN patients and healthy individuals. METHODS: A total of 165 CTN patients and 175 healthy controls, matched for gender and age, were recruited. All subjects underwent magnetic resonance scans. VB-Net was used to locate and segment the bilateral trigeminal nerve of all subjects, followed by the application of radiomics methods for feature extraction, dimensionality reduction, feature selection, model construction, and model evaluation. RESULTS: On the test set for trigeminal nerve segmentation, our segmentation parameters are as follows: the mean Dice Similarity Coefficient (mDCS) is 0.74, the Average Symmetric Surface Distance (ASSD) is 0.64 mm, and the Hausdorff Distance (HD) is 3.34 mm, which are within the acceptable range. Analysis of CTN patients and healthy controls identified 12 features with larger weights, and there was a statistically significant difference in Rad_score between the two groups (p < 0.05). The Area Under the Curve (AUC) values for the three models (Gradient Boosting Decision Tree, Gaussian Process, and Random Forest) are 0.90, 0.87, and 0.86, respectively. After testing with DeLong and McNemar methods, these three models all exhibit good performance in distinguishing CTN from normal individuals. CONCLUSIONS: Radiomics can aid in the clinical diagnosis of CTN, and it is a more objective approach. It serves as a reliable neurobiological indicator for the clinical diagnosis of CTN and the assessment of changes in the trigeminal nerve in patients with CTN.

Altered trends of local brain function in classical trigeminal neuralgia patients after a single trigger pain.

OBJECTIVE: To investigate the altered trends of regional homogeneity (ReHo) based on time and frequency, and clarify the time-frequency characteristics of ReHo in 48 classical trigeminal neuralgia (CTN) patients after a single pain stimulate. METHODS: All patients underwent three times resting-state functional MRI (before stimulation (baseline), after stimulation within 5 s (triggering-5 s), and in the 30th min of stimulation (triggering-30 min)). The spontaneous brain activity was investigated by static ReHo (sReHo) in five different frequency bands and dynamic ReHo (dReHo) methods. RESULTS: In the five frequency bands, the number of brain regions which the sReHo value changed in classical frequency band were most, followed by slow 4 frequency band. The left superior occipital gyrus was only found in slow 2 frequency band and the left superior parietal gyrus was only found in slow 3 frequency band. The dReHo values were changed in midbrain, left thalamus, right putamen, and anterior cingulate cortex, which were all different from the brain regions that the sReHo value altered. There were four altered trends of the sReHo and dReHo, which dominated by decreased at triggering-5 s and increased at triggering-30 min. CONCLUSIONS: The duration of brain function changed was more than 30 min after a single pain stimulate, although the pain of CTN was transient. The localized functional homogeneity has time-frequency characteristic in CTN patients after a single pain stimulate, and the changed brain regions of the sReHo in five frequency bands and dReHo complemented to each other. Which provided a certain theoretical basis for exploring the pathophysiology of CTN.

A 47-Year-old Asian female with tracheobronchial space-occupying lesions caused by chronic lymphocytic leukemia.

CASE PRESENTATION: A 47-year-old Asian woman was admitted with worsening chest tightness and dyspnea for 10 days. Computed tomography (CT) showed changes in the trachea and segmental bronchi. Pulmonary function results suggestive of severe obstructive ventilatory dysfunction. Bronchoscopic findings showed the presence of multiple nodular lesions in the patient's trachea and left and right main bronchi. Bronchoscopic biopsy, lymph node biopsy and bone marrow aspiration flow cytometry test results led to a definitive diagnosis of chronic lymphocytic leukemia (CLL), staged as Binet stage B and Rai stage 2.

Experimental Evaluation of an Ultrasound-Guided High-Intensity-Focused Ultrasound Probe for Sonication of Artery.

OBJECTIVES: This study aimed to develop an ultrasound-guided high-intensity-focused ultrasound (USgHIFU) probe for arterial sonication and to evaluate vascular contraction. METHODS: The USgHIFU probe comprised two confocal spherical transducers for sonication and a US color Doppler flow imaging probe for guidance. A vessel-mimicking phantom was sonicated in two directions. In the vascular radial direction, an isolated rabbit aorta embedded in ex vivo pork liver was sonicated at different acoustic powers (245 and 519 W), flow rates (25, 30, and 50 mL/minute), and sonication energies (519, 980, and 1038 J). Changes in the postsonication vessels were evaluated using US imaging, microscopic observation, and histopathological analysis. RESULTS: Beam focusing along the vascular radial direction caused significant deformation of both tube walls (n = 4), whereas focusing along the axial direction only affected the contraction of the anterior wall (n = 4). The contraction index (Dc) of the vessel sonicated at 245 W and 980 J was 56.2 ± 9.7% (n = 12) with 25 mL/minute. The Dc of the vessel sonicated at 519 W and 1038 J was 56.5 ± 7.8% (n = 17). The Dc of the vessel sonicated at 519 J total energy was 18.3 ± 5.1% (n = 12). CONCLUSION: The developed USgHIFU probe induced greater vascular contractions by covering a larger area of the vessel wall in the radial direction. Sonication energy affects vascular contraction through temperature elevation of the vessel wall. When the acoustic power was high, an increase in acoustic power, even with comparable sonication energy, did not result in greater vessel contraction.

A Comparative Analysis of the Clinical Efficacy of Sacubitril Valsartan Sodium and Enalapril in Patients with Non-Valvular Ejection Fraction Reduction in Heart Failure.

Objective: Heart failure is a common cardiovascular disease, and its prevalence is increasing year by year. For patients with heart failure combined with non-valvular reduced ejection fraction, drug therapy has always been a key treatment. This study aimed to explore the clinical efficacy of sacubitril valsartan sodium and enalapril in such patients. Methods: Study design: This study used a prospective observational design. From February 2020 to February 2022, we included 123 patients with non-valvular heart failure and reduced ejection fraction who were treated in Xingtai Third Hospital. Patients were divided into two groups according to the treatment plan: Group A (n=61) received enalapril, and Group B (n=62) received nifedipine. All patients received conventional treatment. We compared the efficacy of the two groups of patients 8 weeks after treatment. During the study, the laboratory indicators, echocardiographic indicators, cardiovascular markers, and possible adverse reactions of the two groups of patients before and after treatment were recorded. Results: After 8 weeks of treatment, the effective rate of group B was higher than group A (P < .05). There were no differences in the levels of total protein, total bilirubin, total cholesterol and serum creatinine between the two groups before and after treatment (P > .05). The serum creatinine level in the two groups after treatment was higher than that before treatment, and the level in group B was lower than that in group A (P < .05). There were no statistically significant differences in the levels of total protein, total bilirubin and total cholesterol between the two groups before and after treatment (P > .05), and there was no statistically significant difference in the level of serum creatinine between the two groups before treatment (P > .05), and the level of serum creatinine after treatment was higher than that before treatment, and the level of group B was lower than that of group A (P < .05). Before treatment, there was no significant difference in the levels of high-sensitive troponin T and n-terminal brain natriuretic peptide and cyclic guanosine phosphate between the two groups (P > .05). After treatment, the levels of high-sensitive troponin T and N-terminal brain natriuretic peptide in the two groups were lower than those before treatment, and those in group B were lower than those in group A. The level of cyclic guanosine phosphate in group A was lower than that before treatment, the level of cyclic guanosine phosphate in group B was higher than that before treatment, and the level of group B was higher than that of group A (P < .05). The incidence of adverse cardiovascular events in group B was lower than that in group A (P < .05).In this study, the effective rate of treatment group B was significantly higher than that of treatment group A, indicating that treatment group B had a better therapeutic effect. In addition, there were no significant differences between the two groups in a series of biochemical parameters, but it is worth noting that after treatment, the serum creatinine level of group B was significantly lower than that of group A, which may indicate that the treatment of group B is not only more effective but also Reduces the risk of certain adverse cardiovascular events. Conclusion: The main findings of the study showed that Sacubitril valsartan sodium showed better clinical efficacy than enalapril in patients with heart failure and non-valvular reduced ejection fraction. Specifically, the drug significantly improved patients' kidney function, reduced cardiovascular marker levels, and reduced the incidence of adverse cardiovascular events. These findings have important clinical implications for guiding treatment selection in patients with heart failure.