The histone methyltransferase SUV420H2 regulates brown and beige adipocyte thermogenesis.

Activation of brown adipose tissue (BAT) thermogenesis increases energy expenditure and alleviates obesity. Here we discover that histone methyltransferase suppressor of variegation 4-20 homolog 2 (Suv420h2) expression parallels that of Ucp1 in brown and beige adipocytes and that Suv420h2 knockdown significantly reduces, whereas Suv420h2 overexpression significantly increases Ucp1 levels in brown adipocytes. Suv420h2 knockout (H2KO) mice exhibit impaired cold-induced thermogenesis and are prone to diet-induced obesity. In contrast, mice with specific overexpression of Suv420h2 in adipocytes display enhanced cold-induced thermogenesis and are resistant to diet-induced obesity. Further study shows that Suv420h2 catalyzes H4K20 trimethylation at eukaryotic translation initiation factor 4E-binding protein 1 (4e-bp1) promoter, leading to down-regulated expression of 4e-bp1, a negative regulator of the translation initiation complex. This in turn up-regulates PGC1α protein levels, which is associated with increased expression of thermogenic program. We conclude that Suv420h2 is a key regulator of brown/beige adipocyte development and thermogenesis.

Advances in the study of tertiary lymphoid structures in the immunotherapy of breast cancer.

Breast cancer, as one of the most common malignancies in women, exhibits complex and heterogeneous pathological characteristics across different subtypes. Triple-negative breast cancer (TNBC) and HER2-positive breast cancer are two common and highly invasive subtypes within breast cancer. The stability of the breast microbiota is closely intertwined with the immune environment, and immunotherapy is a common approach for treating breast cancer.Tertiary lymphoid structures (TLSs), recently discovered immune cell aggregates surrounding breast cancer, resemble secondary lymphoid organs (SLOs) and are associated with the prognosis and survival of some breast cancer patients, offering new avenues for immunotherapy. Machine learning, as a form of artificial intelligence, has increasingly been used for detecting biomarkers and constructing tumor prognosis models. This article systematically reviews the latest research progress on TLSs in breast cancer and the application of machine learning in the detection of TLSs and the study of breast cancer prognosis. The insights provided contribute valuable perspectives for further exploring the biological differences among different subtypes of breast cancer and formulating personalized treatment strategies.

A combined nomogram based on radiomics and hematology to predict the pathological complete response of neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma.

BACKGROUND: To predict pathological complete response (pCR) in patients receiving neoadjuvant immunochemotherapy (nICT) for esophageal squamous cell carcinoma (ESCC), we explored the factors that influence pCR after nICT and established a combined nomogram model. METHODS: We retrospectively included 164 ESCC patients treated with nICT. The radiomics signature and hematology model were constructed utilizing least absolute shrinkage and selection operator (LASSO) regression, and the radiomics score (radScore) and hematology score (hemScore) were determined for each patient. Using the radScore, hemScore, and independent influencing factors obtained through univariate and multivariate analyses, a combined nomogram was established. The consistency and prediction ability of the nomogram were assessed utilizing calibration curve and the area under the receiver operating factor curve (AUC), and the clinical benefits were assessed utilizing decision curve analysis (DCA). RESULTS: We constructed three predictive models.The AUC values of the radiomics signature and hematology model reached 0.874 (95% CI: 0.819-0.928) and 0.772 (95% CI: 0.699-0.845), respectively. Tumor length, cN stage, the radScore, and the hemScore were found to be independent factors influencing pCR according to univariate and multivariate analyses (P < 0.05). A combined nomogram was constructed from these factors, and AUC reached 0.934 (95% CI: 0.896-0.972). DCA demonstrated that the clinical benefits brought by the nomogram for patients across an extensive range were greater than those of other individual models. CONCLUSIONS: By combining CT radiomics, hematological factors, and clinicopathological characteristics before treatment, we developed a nomogram model that effectively predicted whether ESCC patients would achieve pCR after nICT, thus identifying patients who are sensitive to nICT and assisting in clinical treatment decision-making.

Modified robot-assisted nephroureterectomy with ureteral catheterization for radical resection of the distal ureter: Procedures and short-term outcomes.

Objectives: To describe a bladder cuff excision method modified with ureteral catheterization to better visualize the ureteral orifice during robot-assisted nephroureterectomy (RANU). Methods: We retrospectively analyzed 66 patients with upper urinary tract urothelial carcinoma of the renal pelvis and/or upper-mid ureter treated between January 2020 and January 2023. Among them, 32 patients (group A) underwent RANU supported by ureteral catheterization, and the remaining patients (group B) received routine transperitoneal RANU. Postoperative cystoscopy was performed routinely to compare the rates of residual ureteral orifice between the two groups. Results: Surgeries were completed uneventfully in all 66 patients, without blood transfusion or conversion to open procedures. The operative time, estimated blood loss, and postoperative length of hospital stay were similar between both groups. However, the mean time required for BCE in group A was shorter than that in group B (9.5 min vs. 16.0 min, p = 0.006). Cystoscopy at postoperative three months showed no ipsilateral ureteral orifice in group A, but residual ureteral orifice was found in 23.5% of patients in group B. During a short follow-up period of 16 months, no patients in group A experienced bladder tumor recurrence. However, two patients (5.9%) in group B developed bladder tumor recurrence, with one experiencing local tumor recurrence at the level of the ureteral stump. Conclusions: Our novel technique enables complete ureteral retrieval, accurate and rapid bladder cuff excision, which makes the procedure less invasive and safely reproducible during robot-assisted nephroureterectomy.

Nonlocal erasing and writing of ferroelectric domains using a femtosecond laser in lithium niobate.

We experimentally demonstrate the highly-efficient nonlocal erasing and writing of ferroelectric domains using a femtosecond laser in lithium niobate. Based on the induction of a focused infrared femtosecond laser without any relative displacement or additional treatment, the original multiple ferroelectric domains can be either erased (erasing operation) or elongated (writing operation) simultaneously in the crystal, depending on the laser focusing depth and the laser pulse energy. In the erasing operation, the original multiple ferroelectric domains can be cleared completely by just one laser induction, while in the writing operation, the average length of the ferroelectric domains can be elongated up to 235 µm by three laser inductions. A model has been proposed in which a thermoelectric field and a space charge field are used cooperatively to successfully explain the mechanism of nonlocal erasing and writing. This method greatly improves the efficiency and flexibility of tailoring ferroelectric domain structures, paving the way to large-scale all-optical industrial production for nonlinear photonic crystals and nonvolatile ferroelectric domain wall memories.

Sparse-view cone-beam computed tomography iterative reconstruction based on new multi-gradient direction total variation.

AIM: The accurate reconstruction of cone-beam computed tomography (CBCT) from sparse projections is one of the most important areas for study. The compressed sensing theory has been widely employed in the sparse reconstruction of CBCT. However, the total variation (TV) approach solely uses information from the i-coordinate, j-coordinate, and k-coordinate gradients to reconstruct the CBCT image. MATERIALS AND METHODS: It is well recognized that the CBCT image can be reconstructed more accurately with more gradient information from different directions. Thus, this study introduces a novel approach, named the new multi-gradient direction total variation minimization method. The method uses gradient information from the ij-coordinate, ik-coordinate, and jk-coordinate directions to reconstruct CBCT images, which incorporates nine different types of gradient information from nine directions. RESULTS: This study assessed the efficacy of the proposed methodology using under-sampled projections from four different experiments, including two digital phantoms, one patient's head dataset, and one physical phantom dataset. The results indicated that the proposed method achieved the lowest RMSE index and the highest SSIM index. Meanwhile, we compared the voxel intensity curves of the reconstructed images to assess the edge structure preservation. Among the various methods compared, the curves generated by the proposed method exhibited the highest level of consistency with the gold standard image curves. CONCLUSION: In summary, the proposed method showed significant potential in enhancing the quality and accuracy of CBCT image reconstruction.

Surface-Enhanced Raman Scattering Based on Sb2S3 Microstructures via Femtosecond Laser Direct Writing.

The noble-metal-free surface-enhanced Raman scattering (SERS) substrates have gained significant attention due to their abundant sources, signal uniformity, biocompatibility, and chemical stability. However, the lack of controllable synthesis and fabrication methods for high-SERS-activity noble-metal-free substrates hinders their practical applications. In this study, we demonstrate the use of a femtosecond laser direct writing technique to precisely manipulate and modify microstructures, resulting in enhanced SERS signals from Sb2S3 nonmetal-oxide semiconductor materials. Compared with unpatterned Sb2S3 samples, the Sb2S3 microstructures exhibited up to a 16-fold increase in Raman scattering intensity. Interestingly, our results indicate that the femtosecond laser can induce a transformation in the crystalline state of Sb2S3 and significantly enhance the Raman spectrum signal within the Sb2S3 microstructures. This enhancement is also highly dependent on the period and depth of the microstructures, possibly due to the cavity effects, resulting in a stronger local field enhancement.

Mediation Role of Recreational Physical Activity in the Relationship between the Dietary Intake of Live Microbes and the Systemic Immune-Inflammation Index: A Real-World Cross-Sectional Study.

The main topic of this research is the relationship between dietary intake of live microbe-containing (LMC) foods, recreational physical activity (RPA), and the systemic immune-inflammation index (SII). This study presented a cohort of 26,254 individuals in the National Health and Nutrition Examination Survey (NHANES), representing an estimated weighted population of 193,637,615 in the United States. Weighted multivariable linear regression models were used in consideration of the multi-stage sampling design. Results: The study found that medium-LMC foods were negatively associated with the SII [ß (95% CI): -4.807 (-7.752, -1.862), p = 0.002], indicating that their intake was correlated with lower levels of the SII. However, no significant associations were found with low- or high-LMC foods. The study also explored the relationship between RPA and the SII, finding that more time spent in RPA was negatively associated with the SII [ß (95% CI): -0.022 (-0.034, -0.011), p < 0.001]. A mediation analysis was conducted to investigate the role of RPA in the relationship between medium-LMC food intake and the SII. The analysis revealed that RPA had a notable indirect effect, contributing to 6.7% of the overall change in the SII. Overall, this study suggests that medium-LMC food intake and RPA may have beneficial effects on systemic immune inflammation.

MRI-Based Machine Learning Radiomics for Preoperative Assessment of Human Epidermal Growth Factor Receptor 2 Status in Urothelial Bladder Carcinoma.

BACKGROUND: The human epidermal growth factor receptor 2 (HER2) has recently emerged as hotspot in targeted therapy for urothelial bladder cancer (UBC). The HER2 status is mainly identified by immunohistochemistry (IHC), preoperative and noninvasive methods for determining HER2 status in UBC remain in searching. PURPOSES: To investigate whether radiomics features extracted from MRI using machine learning algorithms can noninvasively evaluate the HER2 status in UBC. STUDY TYPE: Retrospective. POPULATION: One hundred ninety-five patients (age: 68.7 ± 10.5 years) with 14.3% females from January 2019 to May 2023 were divided into training (N = 156) and validation (N = 39) cohorts, and 43 patients (age: 67.1 ± 13.1 years) with 13.9% females from June 2023 to January 2024 constituted the test cohort (N = 43). FIELD STRENGTH/SEQUENCE: 3 T, T2-weighted imaging (turbo spin-echo), diffusion-weighted imaging (breathing-free spin echo). ASSESSMENT: The HER2 status were assessed by IHC. Radiomics features were extracted from MRI images. Pearson correlation coefficient and the least absolute shrinkage and selection operator (LASSO) were applied for feature selection, and six machine learning models were established with optimal features to identify the HER2 status in UBC. STATISTICAL TESTS: Mann-Whitney U-test, chi-square test, LASSO algorithm, receiver operating characteristic analysis, and DeLong test. RESULTS: Three thousand forty-five radiomics features were extracted from each lesion, and 22 features were retained for analysis. The Support Vector Machine model demonstrated the best performance, with an AUC of 0.929 (95% CI: 0.888-0.970) and accuracy of 0.859 in the training cohort, AUC of 0.886 (95% CI: 0.780-0.993) and accuracy of 0.846 in the validation cohort, and AUC of 0.712 (95% CI: 0.535-0.889) and accuracy of 0.744 in the test cohort. DATA CONCLUSION: MRI-based radiomics features combining machine learning algorithm provide a promising approach to assess HER2 status in UBC noninvasively and preoperatively. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Efficacy and Safety Assessment of Intrathoracic Perfusion Chemotherapy Combined with immunological factor Interleukin-2 in the Treatment of Advanced Non-Small Cell Lung Cancer: A Retrospective Cohort Study.

Objective: This study evaluated the efficacy and safety of the gemcitabine and oxaliplatin intrathoracic perfusion chemotherapy (IPCGOR) regimen combined with interleukin-2 (IL-2) for advanced non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective analysis of 460 advanced NSCLC patients from the Yunnan Province Early Cancer Diagnosis and Treatment Project (June 2020-October 2022), assessing the IPCGOR and IL-2 combination. Outcomes were measured based on RECIST 1.1 criteria, focusing on objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (MOS), and treatment safety. Results: The treatment demonstrated an ORR of 67.4%, a DCR of 97.4%, an mPFS of 8.5 months, and an MOS of 12.5 months. 14 patients underwent successful surgery post-treatment. Common adverse reactions were manageable, with no treatment-related deaths reported. Conclusion: The IPCGOR combined with IL-2 regimen shows promising efficacy and a tolerable safety profile for advanced NSCLC. These findings suggest its potential as a reference for treating advanced NSCLC. However, the study's retrospective nature and single-center design pose limitations. Future research should focus on prospective studies, randomized controlled trials, and long-term outcome assessments, particularly in diverse patient subgroups, to further validate and refine the clinical application of this regimen.

Second-harmonic flat-top beam shaping via a three-dimensional nonlinear photonic crystal.

We experimentally extend the nonlinear Gaussian to flat-top beam shaping from one to two dimensions through a three-dimensional nonlinear photonic crystal. Employing a near-infrared femtosecond laser, we induce a modification inside lithium niobate to achieve a second-order nonlinear optical coefficient modulation in three dimensions. The flat-topped truncation of wavefront has been adjusted in a mutual perpendicular coordinate separately. Among the generated flat-topped beams, the optimal flatness is 97.1%, and the nonlinear conversion efficiency is 10-2 at the peak power of 37 kW with the interaction length of 630 µm. By adding an extra dimension, our work simultaneously enables full-wavefront flat-top distribution and nonlinear frequency conversion.

Genomic analyses provide insights into sex differentiation of tetraploid strawberry (Fragaria moupinensis).

The strawberry genus, Fragaria, exhibits a wide range of sexual systems and natural ploidy variation. Nearly, all polyploid strawberry species exhibit separate sexes (dioecy). Research has identified the sex-determining sequences as roughly conserved but with repeatedly changed genomic locations across octoploid strawberries. However, it remains unclear whether tetraploid wild strawberries evolved dioecy independently or shared a common origin with octoploid strawberries. In this study, we investigated the sex determinants of F. moupinensis, a dioecious plant with heterogametic females (ZW). Utilizing a combination of haplotype-resolved genome sequencing of the female F. moupinensis, k-mer-based and coverage-based genome-wide association studies (GWAS), and transcriptomic analysis, we discovered a non-recombining, approximately 33.6 kb W-specific region on chromosome 2a. Within this region, only one candidate sex-determining gene (FmoAFT) was identified. Furthermore, an extensive resequencing of the entire Fragaria genus indicated that the W-specific region displays conservative female specificity across all tetraploid species. This observation suggests that dioecy evolved independently in tetraploid and octoploid strawberries. Moreover, employing virus-induced gene silencing (VIGS), we knocked down the expression of the FmoAFT homologue transcript in cultivated strawberries, revealing its potential role in promoting female functions during early carpel development. We also applied DNA affinity purification sequencing (DAP-seq) and yeast one-hybrid assays to identify potential direct targets of FmoAFT. These insights shed new light on the genetic basis and evolutionary history of sex determination in strawberries, thereby facilitating the formulation of strategies to manipulate sex determination in breeding programs.

Shedding light on the interaction of ovalbumin and resveratrol: structure, digestibility, transport, and allergenicity assessment of OVA-RES complexes.

BACKGROUND: The interaction between food allergens and plant polyphenols has become a safe and effective management strategy to prevent food allergies. Ovalbumin (OVA) is the most abundant allergen in egg whites. Resveratrol (RES) is a plant polyphenol that is abundant in red grapes, berries, and peanuts, and has an anti-allergic effect on allergy-related immune cells. However, there is little information about the effect of RES on the allergenicity of OVA. In this study, the effect of RES on the allergenicity of OVA was investigated. RESULTS: Molecular docking and spectroscopic studies indicated that the addition of RES changed the structure of OVA. The digestion and transfer rate of OVA-RES were effectively improved with an in vitro gastrointestinal digestion model and Caco-2 cell model, especially when the molar ratio of OVA-RES was 1:20. Meanwhile, the KU812 cell degranulation assay proved that the potential allergenicity was remarkably decreased while the molar ratios of OVA-RES were increased to 1:20. Furthermore, hydrogen bonds and van der Waals forces were the dominating forces to stabilize the OVA-RES complexes. CONCLUSION: All the findings demonstrated that the potential allergenicity of OVA was reduced when interacting with RES, and RES can be a potential food material for preparing a hypoallergenic protein, especially for egg allergy. © 2023 Society of Chemical Industry.

A Nomogram of MRI Features to Assess Muscle Invasion in VI-RADS 2 Tumors With Stalk.

BACKGROUND: Vesical Imaging-Reporting and Data System (VI-RADS) is widely used to assess the muscle-invasive status of bladder cancer. However, the current classification efficacy of VI-RASD 2 tumors of stalk is unsatisfactory. PURPOSE: To develop a nomogram to assess muscle-invasive bladder cancer (MIBC) in VI-RADS 2 tumors with stalk. STUDY TYPE: Retrospective. POPULATION: A total of 186 patients (age: 67.8 ± 12.7 years) with 15.1% females, divided randomly into a training cohort (N = 130) and validation cohort (N = 56). FIELD STRENGTH/SEQUENCE: 3-T, T2-weighted imaging (turbo spin-echo), diffusion-weighted imaging (breathing-free spin-echo), and dynamic contrast-enhanced imaging (gradient-echo). ASSESSMENT: Twenty-one MRI features of tumors and stalks were developed from training cohort. The mean apparent diffusion coefficient (ADC) values of the tumor, stalk, and psoas muscles were calculated from the three circular regions of interest. The normalized T value = mean ADC tumor mean ADC muscle . The normalized ST value = mean ADC stalk mean ADC tumor . Three readers assessed the morphology of tumors and stalks. STATISTICAL TESTS: The final features of nomogram were selected by univariable logistic and the least absolute shrinkage and selection operator (LASSO) regression. The performance of the nomogram was assessed by the receiver operating characteristic (ROC) curve, calibration, and decision curve analysis. RESULTS: In VI-RADS 2 tumors with stalk, tumor size over 3 cm, increased stalk width, stalk morphology, decreased normalized T value, and increased normalized ST value were selected as the risk factors for MIBC. The AUC, accuracy, sensitivity, and specificity of the nomogram to assess MIBC were 0.969 (95% CI: 0.941-0.997), 92.3%, 94.1%, and 92.0% in training cohort and 0.940 (95% CI: 0.859-1.000), 89.3%, 75.0%, and 91.7% in validation cohort. DATA CONCLUSION: This study constructed a nomogram for preoperative assessment of MIBC and modifying the current VI-RADS. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Structural Regulation of Photocatalyst to Optimize Hydroxyl Radical Production Pathways for Highly Efficient Photocatalytic Oxidation.

Ring-opening of phenol in wastewater is the pivotal step in photocatalytic degradation. The highly selective generation of catalytical active species (•OH) to facilitate this process presents a significant scientific challenge. Therefore, a novel approach for designing photocatalysts with single-atom containment in metal-covalent organic frameworks (M-COFs) is proposed. The selection of imine-linked COFs containing abundant N and O-chelate sites provides a solid foundation for anchoring metal atom. These dispersed metal atom possess rapid accumulation and transfer capabilities for photogenerated electrons, while the periodic π-conjugated structure in 2D-COFs establishes an effective platform. Additionally, the Lewis acid properties of imine bonds in COFs can enhance the adsorption capacity toward gases with Lewis base properties, such as O2 and N2 . It is demonstrated that the Pd2+ @Tp-TAPT, designed based on this concept, exhibits efficient oxygen adsorption and follows the reaction pathway of O2 →•O2 - →H2 O2 →•OH with high selectivity, thereby achieving completely degradation of refractory phenol through photocatalysis within 10 min. It is anticipated that the selective generation of catalytic active species via advanced material design concepts will serve as a significant reference for achieving precise material catalysis in the future.

Epigenetic and transcriptional landscapes during cerebral cortex development in a microcephaly mouse model.

The cerebral cortex is a pivotal structure integral to advanced brain functions within the mammalian central nervous system. DNA methylation and hydroxymethylation play important roles in regulating cerebral cortex development. However, it remains unclear whether abnormal cerebral cortex development, such as microcephaly, could rescale the epigenetic landscape, potentially contributing to dysregulated gene expression during brain development. In this study, we characterize and compare the DNA methylome/hydroxymethylome and transcriptome profiles of the cerebral cortex across several developmental stages in wild-type (WT) mice and Mcph1 knockout (Mcph1-del) mice with severe microcephaly. Intriguingly, we discover a global reduction of 5'-hydroxymethylcytosine (5hmC) level, primarily in TET1-binding regions, in Mcph1-del mice compared to WT mice during juvenile and adult stages. Notably, genes exhibiting diminished 5hmC levels and concurrently decreased expression are essential for neurodevelopment and brain functions. Additionally, genes displaying a delayed accumulation of 5hmC in Mcph1-del mice are significantly associated with the establishment and maintenance of the nervous system during the adult stage. These findings reveal that aberrant cerebral cortex development in the early stages profoundly alters the epigenetic regulation program, which provides unique insights into the molecular mechanisms underpinning diseases related to cerebral cortex development.

Chemresistive Detection of NO2 of ppb Level in Humid Air at 350 K Using Azo-Spaced Polycroconamide.

Organic molecules are of great interest for gas sensing applications. However, achieving high-performance gas sensors with high sensitivity, fast response, low consumption, and workability in humid conditions is still challenging. Herein, we report the rational design and synthesis of an ion-in-conjugation polymer, PADC (poly-4,4'-azodianiline-croconamide), obtained by the condensation of croconic acid with 4-4'diaminoazobenzene for gas sensing under humid conditions. The as-fabricated PADC-based gas sensor exhibits ultrahigh sensitivity (802.7 ppm-1 at 1 ppm), subppb detection limit, and high selectivity under humid air with an 80% humidity effect at a temperature down to 350 K. PADC shows good planarity, excellent thermostability, and a narrow band gap of 1.2 eV because of azobenzene fragments spacing previously repulsed biphenyl rings. Compared to previous humidity immunity works, PADC-based sensors realized humidity immunity at a relatively lower temperature, resulting in lower energy consumption.

Crosstalk between Gut Sensory Ghrelin Signaling and Adipose Tissue Sympathetic Outflow Regulates Metabolic Homeostasis.

The stomach-derived orexigenic hormone ghrelin is a key regulator of energy homeostasis and metabolism in humans. The ghrelin receptor, growth hormone secretagogue receptor 1a (GHSR), is widely expressed in the brain and gastrointestinal vagal sensory neurons, and neuronal GHSR knockout results in a profoundly beneficial metabolic profile and protects against diet-induced obesity (DIO) and insulin resistance. Here we show that in addition to the well characterized vagal GHSR, GHSR is robustly expressed in gastrointestinal sensory neurons emanating from spinal dorsal root ganglia. Remarkably, sensory neuron GHSR deletion attenuates DIO through increased energy expenditure and sympathetic outflow to adipose tissue independent of food intake. In addition, neuronal viral tract tracing reveals prominent crosstalk between gut non-vagal sensory afferents and adipose sympathetic outflow. Hence, these findings demonstrate a novel gut sensory ghrelin signaling pathway critical for maintaining energy homeostasis.