TOPORS-mediated RAD51 SUMOylation facilitates homologous recombination repair.

Homologous recombination (HR) is critical for error-free repair of DNA double-strand breaks. Chromatin loading of RAD51, a key protein that mediates the recombination, is a crucial step in the execution of the HR repair. Here, we present evidence that SUMOylation of RAD51 is crucial for the RAD51 recruitment to chromatin and HR repair. We found that topoisomerase 1-binding arginine/serine-rich protein (TOPORS) induces the SUMOylation of RAD51 at lysine residues 57 and 70 in response to DNA damaging agents. The SUMOylation was facilitated by an ATM-induced phosphorylation of TOPORS at threonine 515 upon DNA damage. Knockdown of TOPORS or expression of SUMOylation-deficient RAD51 mutants caused reduction in supporting normal RAD51 functions during the HR repair, suggesting the physiological importance of the modification. We found that the SUMOylation-deficient RAD51 reduces the association with its crucial binding partner BRCA2, explaining its deficiency in supporting the HR repair. These findings altogether demonstrate a crucial role for TOPORS-mediated RAD51 SUMOylation in promoting HR repair and genomic maintenance.

Understanding Mental Health Organizations' Instagram Through Visuals: A Content Analysis.

This study analyzed the content, visual features, and audience engagement data of Instagram posts from two mental health organizations over one year (N = 725). For content features, mental health literacy and communicative strategies were examined. Posts that promoted knowledge of mental disorders and treatments, used information and community strategy were more likely to receive higher audience engagement. Visual features of demographic segments, visual composition, and visual framing topics were analyzed. Images that covered an unspecific population, used illustrated images, and focused on anti-stigma topical frames obtained more engagement. Theoretical contributions and practical applications regarding visual message design and management on social media to promote mental health are also offered.

Promoting Mental Health on Social Media: A Content Analysis of Organizational Tweets.

This study analyzed tweets posted over 1 year from three mental-health organizations in the United States, along with audience engagement data of comments, retweets, and likes. The results revealed that tweets focused on mental illnesses or mental health received more engagement than those that emphasized event promotion or relationship building. In addition, there were more gain-framed than loss-framed messages, although the latter triggered more public engagement. Thematic framing was used more frequently than episodic framing and related to higher levels of engagement. Call-to-action (CTA), other audience engaging methods and multimedia strategies were used in various frequencies in these tweets; and the use of CTA, other engaging methods, photos/pictures, and external links, but not videos, were positively related to public engagement. Theoretical contributions and practical implications regarding using social media for mental health promotion were offered.

Deep Neural Network Pretrained by Weighted Autoencoders and Transfer Learning for Retention Time Prediction of Small Molecules.

Retention time (RT) prediction contributes to identification of small molecules measured by high-performance liquid chromatography coupled with high-resolution mass spectrometry. Deep learning algorithms based on big data can enhance the accuracy of RT prediction. But at different chromatographic conditions, RTs of compounds are different, and the number of compounds with known RTs is small in most cases. Therefore, the transfer of big data is necessary. In this work, a strategy using a deep neural network (DNN) pretrained by weighed autoencoders and transfer learning (DNNpwa-TL) was proposed to efficiently predict RTs of compounds. The loss function in the autoencoders was calculated with features weighted by mutual information. Then, a DNN pretrained by weighted autoencoders (DNNpwa) was produced. For other specific chromatographic methods, the transfer learning model DNNpwa-TLs were built through fine-tuning the DNNpwa with the help of some compounds with known RTs to conduct the RT prediction. With the above strategy, a DNNpwa was first built with the METLIN small molecule retention time data set containing 80 038 small molecule compounds. A median relative error of 3.1% and a mean relative error of 4.9% were achieved. Then, 17 data sets from different chromatographic methods were studied, and the results showed that the performance of DNNpwa-TL was better than those of other deep learning models. Besides, DNNpwa-TL outperformed random forest, gradient boost, least absolute shrinkage and selection operator regression, and DNN for most of the 17 data sets. Therefore, DNNpwa-TL can provide an efficient method to perform RT prediction of small molecule compounds for different chromatographic methods and conditions.

Preparation of MOF Film/Aerogel Composite Catalysts via Substrate-Seeding Secondary-Growth for the Oxygen Evolution Reaction and CO2 Cycloaddition.

Substrate-supported metal-organic frameworks (MOFs) films are desired to realize their potential in practical applications. Herein, a novel substrate-seeding secondary-growth strategy is developed to prepare composites of uniform MOFs films on aerogel walls. Briefly, the organic ligand is "pre-seeded" onto the aerogel walls, and then a small amount of metal-ion solution is sprayed onto the prepared aerogel. The sprayed solution diffuses along the aerogel walls to form a continuous thin layer, which confines the nucleation reaction, promoting the formation of uniform MOFs films on the aerogel walls. The whole process is simple in operation, highly efficient, and eco-friendly. The resulting hierarchical MOFs/aerogel composites have abundant accessible active sites and enable excellent mass transfer, which endows the composite with outstanding catalytic activity and stability in both liquid-phase CO2 cycloaddition and electrochemical oxygen evolution reaction (OER) process.

Nonreciprocal Heat Circulation Metadevices.

Thermal nonreciprocity typically stems from nonlinearity or spatiotemporal variation of parameters. However, constrained by the inherent temperature-dependent properties and the law of mass conservation, previous works have been compelled to treat dynamic and steady-state cases separately. Here, by establishing a unified thermal scattering theory, the creation of a convection-based thermal metadevice which supports both dynamic and steady-state nonreciprocal heat circulation is reported. The nontrivial dependence between the nonreciprocal resonance peaks and the dynamic parameters is observed and the unique nonreciprocal mechanism of multiple scattering is revealed at steady state. This mechanism enables thermal nonreciprocity in the initially quasi-symmetric scattering matrix of the three-port metadevice and has been experimentally validated with a significant isolation ratio of heat fluxes. The findings establish a framework for thermal nonreciprocity that can be smoothly modulated for dynamic and steady-state heat signals, it may also offer insight into other heat-transfer-related problems or even other fields such as acoustics and mechanics.

The Effectiveness of Traditional Chinese Medicine in Treating Malignancies via Regulatory Cell Death Pathways and the Tumor Immune Microenvironment: A Review of Recent Advances.

Traditional Chinese Medicine (TCM) has achieved high clinical efficacy in treating malignancies in recent years and is thus gradually becoming an important therapy for patients with advanced tumor for its benefits in reducing side effects and improving patients' immune status. However, it has not been internationally recognized for cancer treatment because TCM's anti-tumor mechanism is not fully elucidated, limiting its clinical application and international promotion. This review traced the mechanism of the TCM-mediated tumor cell death pathway and its effect on remodeling the tumor immune microenvironment, its direct impact on the microenvironment, its anti-tumor effect in combination with immunotherapy, and the current status of clinical application of TCM on tumor treatment. TCM can induce tumor cell death in many regulatory cell death (RCD) pathways, including apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis. In addition, TCM-induced cell death could increase the immune cells' infiltration with an anti-tumor effect in the tumor tissue and elevate the proportion of these cells in the spleen or peripheral blood, enhancing the anti-tumor capacity of the tumor-bearing host. Moreover, TCM can directly affect immune function by increasing the population or activating the sub-type immune cells with an anti-tumor role. It was concluded that TCM could induce a pan-tumor death modality, remodeling the local TIME differently. It can also improve the systemic immune status of tumor-bearing hosts. This review aims to establish a theoretical basis for the clinical application of TCM in tumor treatment and to provide a reference for TCM's potential in combination with immunotherapy in cancer treatment.

Observation of parity-time symmetry in diffusive systems.

Phase modulation has scarcely been mentioned in diffusive physical systems because the diffusion process does not carry the momentum like waves. Recently, non-Hermitian physics provides a unique perspective for understanding diffusion and shows prospects in thermal phase regulation, exemplified by the discovery of anti-parity-time (APT) symmetry in diffusive systems. However, precise control of thermal phase remains elusive hitherto and can hardly be realized, due to the phase oscillations. Here we construct the PT-symmetric diffusive systems to achieve the complete suppression of thermal phase oscillation. The real coupling of diffusive fields is readily established through a strong convective background, and the decay-rate detuning is enabled by thermal metamaterial design. We observe the phase transition of PT symmetry breaking with the symmetry-determined amplitude and phase regulation of coupled temperature fields. Our work shows the existence of PT symmetry in dissipative energy exchanges and provides unique approaches for harnessing the mass transfer of particles, wave dynamics in strongly scattering systems, and thermal conduction.

Challenges in clinical practice, biological mechanism and prospects of physical ablation therapy for COPD.

Chronic obstructive pulmonary disease (COPD) is projected to become the third leading cause of death globally by 2030. Despite the limited treatment options available for advanced COPD, which are mostly restricted to costly lung transplants, physical ablation therapy offers promising alternatives. This technique focuses on ablating lesioned airway epithelium, reducing secretions and obstructions, and promoting normal epithelial regeneration, demonstrating significant therapeutic potential. Physical ablation therapy primarily involves thermal steam ablation, cryoablation, targeted lung denervation, and high-voltage pulsed electric field ablation. These methods help transform the hypersecretory phenotype, alleviate airway inflammation, and decrease the volume of emphysematous lung segments by targeting goblet cells and damaged lung areas. Compared to traditional treatments, endoscopic physical ablation offers fewer injuries, quicker recovery, and enhanced safety. However, its application in COPD remains limited due to inconsistent clinical outcomes, a lack of well-understood mechanisms, and the absence of standardized guidelines. This review begins by exploring the development of these ablation techniques and their current clinical uses in COPD treatment. It then delves into the therapeutic effects reported in recent clinical studies and discusses the underlying mechanisms. Finally, the review assesses the future prospects and challenges of employing ablation technology in COPD clinical practice, aiming to provide a practical reference and a theoretical basis for its use and inspire further research.

Advantages of pulsed electric field ablation for COPD: Excellent killing effect on goblet cells.

Mucus hypersecretion resulting from excessive proliferation and metaplasia of goblet cells in the airways is the pathological foundation for Chronic obstructive pulmonary disease (COPD). Clinical trials have confirmed the clinical efficacy of pulsed electric field ablation (PFA) for COPD, but its underlying mechanisms is poorly understood. Cellular and animal models of COPD (rich in goblet cells) were established in this study to detect goblet cells' sensitivity to PFA. Schwan's equation was adopted to calculate the cells' transmembrane potential and the electroporation areas in the cell membrane. We found that goblet cells are more sensitive to low-intensity PFA (250 V/cm-500 V/cm) than BEAS-2B cells. It is attributed to the larger size of goblet cells, which allows a stronger transmembrane potential formation under the same electric field strength. Additionally, the transmembrane potential of larger-sized cells can reach the cell membrane electroporation threshold in more areas. Trypan blue staining confirmed that the cells underwent IRE rate was higher in goblet cells than in BEAS-2B cells. Animal experiments also confirmed that the airway epithelium of COPD is more sensitive to PFA. We conclude that lower-intensity PFA can selectively kill goblet cells in the COPD airway epithelium, ultimately achieving the therapeutic effect of treating COPD.

Different modifiable risk factors for the development of non-advanced adenoma, advanced adenomatous lesion, and sessile serrated lesions, on screening colonoscopy.

The development of premalignant colorectal polyps is significantly influenced by various lifestyle and modifiable risk factors. In our study, we used a large cohort of 9025 patients, who underwent screening colonoscopies at a university hospital, to assess the risk factors associated with the development of three different colorectal cancer precursor lesions: non-advanced adenomas (NAs), advanced adenomatous lesions (ADLs), and sessile serrated lesions (SSLs). Among the participants, 3641 had NAs, 836 had ADLs, and 533 had SSLs. We identified obesity, current smoking, and appendicular skeletal muscle mass as modifiable lifestyle risk factors that increase the development of NAs and ADLs (all P < 0.05). Furthermore, we found a positive correlation between the degree of obesity and an increased risk of developing NAs and ADLs (all P for trend < 0.001), while non-smoking was associated with a decreased risk (P for trend < 0.001 and 0.003, respectively). Smoking was the only modifiable risk factor for developing SSLs (adjusted odds ratio [aOR] 1.58; 95% confidence interval [CI] 1.20-2.07), and the risk was even higher in patients with metabolic syndrome (aOR 1.71; 95% CI 1.05-2.77). Addressing modifiable lifestyle factors such as smoking and obesity could play an important role in reducing the risk of both non-advanced and advanced adenomatous lesions. Smoking cessation is especially important as it is a significant modifiable risk factor for sessile serrated lesions.

Convective Thermal Metamaterials: Exploring High-Efficiency, Directional, and Wave-Like Heat Transfer.

Convective thermal metamaterials are artificial structures where convection dominates in the thermal process. Due to the field coupling between velocity and temperature, convection provides a new knob for controlling heat transfer beyond pure conduction, thus allowing active and robust thermal modulations. With the introduced convective effects, the original parabolic Fourier heat equation for pure conduction can be transformed to hyperbolic. Therefore, the hybrid diffusive system can be interpreted in a wave-like fashion, reviving many wave phenomena in dissipative diffusion. Here, recent advancements in convective thermal metamaterials are reviewed and the state-of-the-art discoveries are classified into the following four aspects, enhancing heat transfer, porous-media-based thermal effects, nonreciprocal heat transfer, and non-Hermitian phenomena. Finally, a prospect is cast on convective thermal metamaterials from two aspects. One is to utilize the convective parameter space to explore topological thermal effects. The other is to further broaden the convective parameter space with spatiotemporal modulation and multi-physical effects.

Ongoing involvers and promising therapeutic targets of hepatic fibrosis: The hepatic immune microenvironment.

Hepatic fibrosis is often secondary to chronic inflammatory liver injury. During the development of hepatic fibrosis, the damaged hepatocytes and activated hepatic stellate cells (HSCs) caused by the pathogenic injury could secrete a variety of cytokines and chemokines, which will chemotactic innate and adaptive immune cells of liver tissue and peripheral circulation infiltrating into the injury site, mediating the immune response against injury and promoting tissue reparation. However, the continuous release of persistent injurious stimulus-induced inflammatory cytokines will promote HSCs-mediated fibrous tissue hyperproliferation and excessive repair, which will cause hepatic fibrosis development and progression to cirrhosis even liver cancer. And the activated HSCs can secrete various cytokines and chemokines, which directly interact with immune cells and actively participate in liver disease progression. Therefore, analyzing the changes in local immune homeostasis caused by immune response under different pathological states will greatly enrich our understanding of liver diseases' reversal, chronicity, progression, and even deterioration of liver cancer. In this review, we summarized the critical components of the hepatic immune microenvironment (HIME), different sub-type immune cells, and their released cytokines, according to their effect on the development of progression of hepatic fibrosis. And we also reviewed and analyzed the specific changes and the related mechanisms of the immune microenvironment in different chronic liver diseases.Moreover, we retrospectively analyzed whether the progression of hepatic fibrosis could be alleviated by modulating the HIME.We aimed to elucidate the pathogenesis of hepatic fibrosis and provide the possibility for exploring the therapeutic targets for hepatic fibrosis.

Ectopic Expression of Gastrodia Antifungal Protein in Rice Enhances Resistance to Rice Sheath Blight Disease.

Sheath blight (ShB) disease, caused by Rhizoctonia solani Kühn, is one of the most serious rice diseases. Rice breeding against ShB has been severely hindered because no major resistance genes or germplasms are available in rice. Here, we report that introduction of Gastrodia antifungal protein (GAFP) genes from Gastrodia elata B1 into rice significantly enhances resistance to rice ShB. Four GAFP genes were cloned from G. elata B1, and all displayed a strong ability to inhibit R. solani growth in plate assays. Two versions, with or without a signal peptide, for each of the four GAFP genes were introduced into XD3 and R6547 rice cultivars, and all transgenic lines displayed stronger ShB resistance than the corresponding wild-type control in both greenhouse and field conditions. Importantly, GAFP2 showed the highest ShB resistance; GAFPs with and without its signal peptide showed no significant differences in enhancing ShB resistance. We also evaluated the agronomic traits of these transgenic rice and found that ectopic expression of GAFPs in rice at appropriate levels did not affect agronomic traits other than enhancing ShB resistance. Together, these results indicate that GAFP genes, especially GAFP2, have great potential in rice breeding against ShB disease.

Using a Deep Learning Model to Address Interobserver Variability in the Evaluation of Ulcerative Colitis (UC) Severity.

The use of endoscopic images for the accurate assessment of ulcerative colitis (UC) severity is crucial to determining appropriate treatment. However, experts may interpret these images differently, leading to inconsistent diagnoses. This study aims to address the issue by introducing a standardization method based on deep learning. We collected 254 rectal endoscopic images from 115 patients with UC, and five experts in endoscopic image interpretation assigned classification labels based on the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scoring system. Interobserver variance analysis of the five experts yielded an intraclass correlation coefficient of 0.8431 for UCEIS scores and a kappa coefficient of 0.4916 when the UCEIS scores were transformed into UC severity measures. To establish a consensus, we created a model that considered only the images and labels on which more than half of the experts agreed. This consensus model achieved an accuracy of 0.94 when tested with 50 images. Compared with models trained from individual expert labels, the consensus model demonstrated the most reliable prediction results.

Clinical outcomes of acute upper gastrointestinal bleeding according to the risk indicated by Glasgow-Blatchford risk score-computed tomography score in the emergency room.

BACKGROUND/AIMS: Acute upper gastrointestinal (UGI) bleeding is a significant emergency situation with a mortality rate of 2% to 10%. Therefore, initial risk stratification is important for proper management. We aimed to evaluate the role of contrast-enhanced multidetector computed tomography (MDCT) for risk stratification in patients with acute UGI bleeding in the emergency room (ER). METHODS: This retrospective study included patients with UGI bleeding in the ER. Glasgow-Blatchford risk score-computed tomography (GBS-CT) was assessed using a combination of GBS and the MDCT scan scoring system. RESULTS: Of the 297 patients with UGI bleeding, 124 (41.8%) underwent abdominal MDCT. Among them, 90.3% were classified as high-risk by GBS, and five patients died (4.0%). Rebleeding occurred in nine patients (7.3%). The high-risk GBS-CT group had significantly higher in-hospital mortality (10.5% in high-risk vs. 1.4% in moderate risk vs. 0% in low-risk, p = 0.049), transfusion amount (p < 0.001), and endoscopic hemostasis (p < 0.001) compared to the moderate- and low-risk groups. CONCLUSION: Adding MDCT scans to the existing validated prognosis model when predicting the risk of UGI bleeding in patients in the ER plays a significant role in determining in-hospital mortality, transfusions, and the need for endoscopic hemostasis.

Genome-wide signatures of mammalian skin covering evolution.

Animal body coverings provide protection and allow for adaptation to environmental pressures such as heat, ultraviolet radiation, water loss, and mechanical forces. Here, using a comparative genomics analysis of 39 mammal species spanning three skin covering types (hairless, scaly and spiny), we found some genes (e.g., UVRAG, POLH, and XPC) involved in skin inflammation, skin innate immunity, and ultraviolet radiation damage repair were under selection in hairless ocean mammals (e.g., whales and manatees). These signatures might be associated with a high risk of skin diseases from pathogens and ultraviolet radiation. Moreover, the genomes from three spiny mammal species shared convergent genomic regions (EPHB2, EPHA4, and NIN) and unique positively selected genes (FZD6, INVS, and CDC42) involved in skin cell polarity, which might be related to the development of spines. In scaly mammals, the shared convergent genomic regions (e.g., FREM2) were associated with the integrity of the skin epithelium and epidermal adhesion. This study identifies potential convergent genomic features among distantly related mammals with the same skin covering type.

Small Bowel Necrosis Associated with Catastrophic Antiphospholipid Syndrome: A Case Report.

Catastrophic antiphospholipid syndrome is a highly fatal condition characterized by widespread thromboembolism subsequent to a triggering factor (e.g., infection, trauma, and neoplasia) in antiphospholipid antibody-positive patients. This paper reports a case of a 29-year-old male without the underlying disease who developed extensive mesenteric thromboembolism and jejunal necrosis during the treatment for acute enteritis. The patient's condition was improved with low-molecular-weight heparin and an intravenous Ig treatment with emergency surgery. The serum antiphospholipid (anticardiolipin IgM) and lupus anticoagulant antibody tests showed positive results. Acute infectious enterocolitis is generally considered a mild disease. On the other hand, aggressive evaluation and treatment should be considered if the clinical conditions do not improve and deteriorate rapidly despite appropriate antibiotic treatment because of the possibility of acute immunological complications, such as catastrophic antiphospholipid syndrome.

A graph density-based strategy for features fusion from different peak extract software to achieve more metabolites in metabolic profiling from high-resolution mass spectrometry.

In metabolomics study, it is not easy to extract the metabolites from data of ultra high-performance liquid chromatography-high-resolution mass spectrometry, especially for those with low abundance. Different software for peak recognition and matching use different algorithms, leading to different extract results. Therefore, integration of results from different software can obtain richer metabolome information, but the redundant features should be removed. In this study, an integrated strategy of fusing features and removing redundancy based on graph density (FRRGD) was proposed. A graph is used to cover the ion features generated by two open access software (XCMS, MZmine 2) and a software (SIEVE) from an instrument vendor, and redundant features were removed by searching the maximal complete sub-graphs. A standard mixture containing 41 metabolites and a spontaneous urine were utilized to develop the method and demonstrate its usefulness. For the standard mixture, 19, 19 and 27 metabolites were extracted by XCMS, MZmine 2 and SIEVE, respectively. After fusion by FRRGD, 37 metabolites were obtained. For the diluted spontaneous urine sample, 1103, 1500 and 387 metabolites were extracted by XCMS, MZmine 2 and SIEVE, respectively, FRRGD produced 1619 metabolites which were much more than individual software, significantly increasing metabolome coverage. The proposed FRRGD shows a great prospect as a new data processing strategy for metabolomics study.

Round Acupuncture for the Treatment of Recurrent Carpal Tunnel Syndrome.

OBJECTIVES: Round Acupuncture having blunt end has developed from acupotomy. This case report is to find out that Round Acupuncture is effective in treating patients with recurrent carpal tunnel syndrome (CTS), which has not improved by steroid injection or acupotomy. METHODS: Round Acupuncture was inserted into the distal fibers of transverse carpal ligament and released toward the proximal fibers. Treatment was performed three times in total. T ingling, numbn ess, night pain and swelling sensation were assessed, and provocative maneuvers were also used. RESULTS: After treat ment, all symptoms completely disappeared and the patient had no recurrence until 3 months after treatment. CONCLUSION: Round Acupuncture co uld be an effective treatment for recurrent CTS.