Catalytic Dual-Mode Immunotherapy: Anisotropic AuPt Heterostructure Decorated with Starry Pt Nanoclusters for Robust Cancer Photometalloimmunotherapy.

To overcome current limitations in photoimmunotherapy, such as insufficient tumor antigen generation and a subdued immune response, a novel photo-/metallo dual-mode immunotherapeutic agent (PMIA) is introduced for potent near-infrared (NIR) light-triggered cancer therapy. PMIA features a dumbbell-like AuPt heterostructure decorated with starry Pt nanoclusters, meticulously engineered for enhancing plasmonic catalysis through multi-dimensional regulation of Pt growth on Au nanorods. Under NIR laser exposure, end-tipped Pt nanoclusters induce efficient electron-hole spatial separation along the longitudinal axis, resulting in radial and axial electron distribution polarization, conferring unique anisotropic properties to PMIA. Additionally, starry Pt nanoclusters on the sides of Au nanorods augment the local electron enrichment field. Validated through finite-difference time-domain analysis and Raman scattering, this configuration fosters local electron enrichment, facilitating robust reactive oxygen species generation for potent photoimmunotherapy. Moreover, Pt nanoclusters facilitate Pt2+ ion release, instigating intranuclear DNA damage and inducing synergistic immunogenic cell death (ICD) for metalloimmunotherapy. Consequently, PMIA elicits abundant danger-associated molecular patterns, promotes T cell infiltration, and triggers systemic immune responses, effectively treating primary and distant tumors, inhibiting metastasis in vivo. This study unveils a pioneering dual-mode ICD amplification strategy driven by NIR light, synergistically integrating photoimmunotherapy and metalloimmunotherapy, culminating in potent cancer photometalloimmunotherapy.

NKUT: Dataset and Benchmark for Pediatric Mandibular Wisdom Teeth Segmentation.

Germectomy is a common surgery in pediatric dentistry to prevent the potential dangers caused by impacted mandibular wisdom teeth. Segmentation of mandibular wisdom teeth is a crucial step in surgery planning. However, manually segmenting teeth and bones from 3D volumes is time-consuming and may cause delays in treatment. Deep learning based medical image segmentation methods have demonstrated the potential to reduce the burden of manual annotations, but they still require a lot of well-annotated data for training. In this paper, we initially curated a Cone Beam Computed Tomography (CBCT) dataset, NKUT, for the segmentation of pediatric mandibular wisdom teeth. This marks the first publicly available dataset in this domain. Second, we propose a semantic separation scale-specific feature fusion network named WTNet, which introduces two branches to address the teeth and bones segmentation tasks. In WTNet, We design a Input Enhancement (IE) block and a Teeth-Bones Feature Separation (TBFS) block to solve the feature confusions and semantic-blur problems in our task. Experimental results suggest that WTNet performs better on NKUT compared to previous state-of-the-art segmentation methods (such as TransUnet), with a maximum DSC lead of nearly 16%. Dataset and codes will be released at https://github.com/nkicsl/NKUT.

Deep learning-assisted diagnosis of large vessel occlusion in acute ischemic stroke based on four-dimensional computed tomography angiography.

Purpose: To develop deep learning models based on four-dimensional computed tomography angiography (4D-CTA) images for automatic detection of large vessel occlusion (LVO) in the anterior circulation that cause acute ischemic stroke. Methods: This retrospective study included 104 LVO patients and 105 non-LVO patients for deep learning models development. Another 30 LVO patients and 31 non-LVO patients formed the time-independent validation set. Four phases of 4D-CTA (arterial phase P1, arterial-venous phase P2, venous phase P3 and late venous phase P4) were arranged and combined and two input methods was used: combined input and superimposed input. Totally 26 models were constructed using a modified HRNet network. Assessment metrics included the areas under the curve (AUC), accuracy, sensitivity, specificity and F1 score. Kappa analysis was performed to assess inter-rater agreement between the best model and radiologists of different seniority. Results: The P1 + P2 model (combined input) had the best diagnostic performance. In the internal validation set, the AUC was 0.975 (95%CI: 0.878-0.999), accuracy was 0.911, sensitivity was 0.889, specificity was 0.944, and the F1 score was 0.909. In the time-independent validation set, the model demonstrated consistently high performance with an AUC of 0.942 (95%CI: 0.851-0.986), accuracy of 0.902, sensitivity of 0.867, specificity of 0.935, and an F1 score of 0.901. The best model showed strong consistency with the diagnostic efficacy of three radiologists of different seniority (k = 0.84, 0.80, 0.70, respectively). Conclusion: The deep learning model, using combined arterial and arterial-venous phase, was highly effective in detecting LVO, alerting radiologists to speed up the diagnosis.

Polyphenol-Assisted Biomineralization of Metal-Organic Framework Nanoparticles for Precision Delivery of Therapeutic Proteins to Cancer Cells.

The delivery of proteins into the cytosol holds great promise for cell signaling manipulation and the development of precision medicine. However, this potency is challenged by achieving targeted and controlled delivery, specifically within diseased cells. In this study, we introduce a versatile and effective method for the precision delivery of therapeutic proteins to cancer cells by designing polyphenol-assisted biomineralization of zeolite imidazole framework-8 (ZIF-8). We demonstrate that by leveraging the strong noncovalent binding affinity of epigallocatechin gallate (EGCG) with both proteins and ZIF-8, our approach significantly enhances the biomineralization of ZIF-8, which in turn improves the efficiency of protein encapsulation and intracellular delivery. Moreover, the incorporation of EGCG within ZIF-8 enables controlled degradation of the nanoparticles and the selective release of the encapsulated proteins in cancer cells. This selective release is triggered by the oxidation of EGCG in response to the high levels of reactive oxygen species (ROS) found within cancer cells that destabilize the EGCG/ZIF-8 nanoparticles. We have further demonstrated the ability of EGCG/ZIF-8 to deliver a wide range of proteins into cancer cells, including bacterial virulence protein, to rewire cell signaling and prohibit tumor cell growth in a mouse xenograft model. Our strategy and findings underscore the potential of designing the EGCG/ZIF-8 interface for specific and controlled protein delivery for targeted cancer therapy.

Melanoma differentiation-associated protein 5 prevents cardiac hypertrophy via apoptosis signal-regulating kinase 1-c-Jun N-terminal kinase/p38 signaling.

Pathological cardiac hypertrophy (CH) is driven by maladaptive changes in myocardial cells in response to pressure overload or other stimuli. CH has been identified as a significant risk factor for the development of various cardiovascular diseases, ultimately resulting in heart failure. Melanoma differentiation-associated protein 5 (MDA5), encoded by interferon-induced with helicase C domain 1 (IFIH1), is a cytoplasmic sensor that primarily functions as a detector of double-stranded ribonucleic acid (dsRNA) viruses in innate immune responses; however, its role in CH pathogenesis remains unclear. Thus, the aim of this study was to examine the relationship between MDA5 and CH using cellular and animal models generated by stimulating neonatal rat cardiomyocytes with phenylephrine and by performing transverse aortic constriction on mice, respectively. MDA5 expression was upregulated in all models. MDA5 deficiency exacerbated myocardial pachynsis, fibrosis, and inflammation in vivo, whereas its overexpression hindered CH development in vitro. In terms of the underlying molecular mechanism, MDA5 inhibited CH development by promoting apoptosis signal-regulating kinase 1 (ASK1) phosphorylation, thereby suppressing c-Jun N-terminal kinase/p38 signaling pathway activation. Rescue experiments using an ASK1 activation inhibitor confirmed that ASK1 phosphorylation was essential for MDA5-mediated cell death. Thus, MDA5 protects against CH and is a potential therapeutic target.

Stable hydrogen evolution reaction at high current densities via designing the Ni single atoms and Ru nanoparticles linked by carbon bridges.

Continuous and effective hydrogen evolution under high current densities remains a challenge for water electrolysis owing to the rapid performance degradation under continuous large-current operation. In this study, theoretical calculations, operando Raman spectroscopy, and CO stripping experiments confirm that Ru nanocrystals have a high resistance against deactivation because of the synergistic adsorption of OH intermediates (OHad) on the Ru and single atoms. Based on this conceptual model, we design the Ni single atoms modifying ultra-small Ru nanoparticle with defect carbon bridging structure (UP-RuNiSAs/C) via a unique unipolar pulse electrodeposition (UPED) strategy. As a result, the UP-RuNiSAs/C is found capable of running steadily for 100 h at 3 A cm-2, and shows a low overpotential of 9 mV at a current density of 10 mA cm-2 under alkaline conditions. Moreover, the UP-RuNiSAs/C allows an anion exchange membrane (AEM) electrolyzer to operate stably at 1.95 Vcell for 250 h at 1 A cm-2.

Knowledge mapping of digital medicine in cardiovascular diseases from 2004 to 2022: A bibliometric analysis.

Objective: To review studies on digital medicine in cardiovascular diseases (CVD), discuss its development process, knowledge structure and research hotspots, and provide a perspective for researchers in this field. Methods: The relevant literature in recent 20 years (January 2004 to October 2022) were retrieved from the Web of Science Core Collection (WoSCC). CiteSpace was used to demonstrate our knowledge of keywords, co-references and speculative frontiers. VOSviewer was used to chart the contributions of authors, institutions and countries and incorporates their link strength into the table. Results: A total of 5265 English articles in set timespan were included. The number of publications increased steadily annually. The United States (US) produced the highest number of publications, followed by England. Most publications were from Harvard Medicine School, followed by Massachusetts General Hospital and Brigham Women's Hospital. The most authoritative academic journal was JMIR mHealth and uHealth. Noseworthy PA may have the highest influence in this intersected field with the highest number of citations and total link strength. The utilization of wearable mobile devices in the context of CVD, encompassing the identification of risk factors, diagnosis and prevention of diseases, as well as early intervention and remote management of diseases, has been widely acknowledged as a knowledge base and an area of current interest. To investigate the impact of various digital medicine interventions on chronic care and assess their clinical effectiveness, examine the potential of machine learning (ML) in delivering clinical care for atrial fibrillation (AF) and identifying early disease risk factors, as well as explore the development of disease prediction models using neural networks (NNs), ML and unsupervised learning in CVD prognosis, may emerge as future trends and areas of focus. Conclusion: Recently, there has been a significant surge of interest in the investigation of digital medicine in CVD. This initial bibliometric study offers a comprehensive analysis of the research landscape pertaining to digital medicine in CVD, thereby furnishing related scholars with a dependable reference to facilitate further progress in this domain.

Ferritin-nanocaged aggregation-induced emission nanoaggregates for NIR-II fluorescence-guided noninvasive, controllable male contraception.

Controllable contraception in male animals was demonstrated through the utilization of gold nanorods' photothermal effect to accomplish mild testicular hyperthermia. However, the challenges arising from testicular administration and the non-biodegradability of nanoparticles hinder further clinical implementation. Therefore, a straightforward, non-invasive, and enhanced contraception approach is required. This study explores the utilization of human heavy chain ferritin (HFn) nanocarriers loaded with aggregation-induced emission luminogens (AIEgens) for noninvasive, controllable male contraception guided by Near-Infrared-II (NIR-II) fluorescence imaging. The HFn-caged AIEgens (HFn@BBT) are delivered via intravenous injection and activated by near-infrared irradiation. Lower hyperthermia treatment induces partial damage to the testes and seminiferous tubules, reducing fertility indices by approximately 100% on the 7th day, which gradually recovers to 80% on the 60th day. Conversely, implementation of elevated hyperthermia therapy causes total destruction of both testes and seminiferous tubules, leading to a complete loss of fertility on the 60th day. Additionally, the use of AIEgens in NIR-II imaging offers improved fluorescence efficiency and penetration depth. The findings of this study hold significant promise for the advancement of safe and effective male contraceptive methods, addressing the need for noninvasive and controllable approaches to reproductive health and population control.

Testicular volume is a noninvasive predictor of sperm retrieval failure in idiopathic nonobstructive azoospermia.

ABSTRACT: We investigated the prognostic importance of noninvasive factors in predicting sperm retrieval failure in idiopathic nonobstructive azoospermia (iNOA). We studied 193 patients with nonobstructive azoospermia who underwent microsurgical testicular sperm extraction. The Chi-square test and Mann-Whitney U tests for clinical parameters and seminiferous tubule distribution were used for between-group comparisons. A logistic regression analysis was conducted to identify predictors of retrieval failure. Area under the receiver operating characteristic curve for each variable was evaluated, and the net clinical benefit was calculated using a clinical decision curve. Patients with iNOA had a lower sperm retrieval rate than those with known causes. Moreover, testicular volume was an independent factor affecting sperm extraction outcomes (odds ratio = 0.79, P < 0.05). The testicular volume cut-off value was 6.5 ml (area under the curve: 0.694). The patients with iNOA were categorized into two groups on the basis of the distribution of seminiferous tubules observed. The sperm retrieval rate and testicular volume were significantly different between the groups with a uniform or heterogeneous tubule distribution. There was also a significant association between a uniform tubule distribution and testicular volume. In conclusion, a testicular volume of more than 6.5 ml effectively predicts microsurgical testicular sperm extraction failure due to a uniform tubule distribution in patients with iNOA.

LVONet: automatic classification model for large vessel occlusion based on the difference information between left and right hemispheres.

Objective.Stroke is a highly lethal condition, with intracranial vessel occlusion being one of its primary causes. Intracranial vessel occlusion can typically be categorized into four types, each requiring different intervention measures. Therefore, the automatic and accurate classification of intracranial vessel occlusions holds significant clinical importance for assessing vessel occlusion conditions. However, due to the visual similarities in shape and size among different vessels and variations in the degree of vessel occlusion, the automated classification of intracranial vessel occlusions remains a challenging task. Our study proposes an automatic classification model for large vessel occlusion (LVO) based on the difference information between the left and right hemispheres.Approach.Our approach is as follows. We first introduce a dual-branch attention module to learn long-range dependencies through spatial and channel attention, guiding the model to focus on vessel-specific features. Subsequently, based on the symmetry of vessel distribution, we design a differential information classification module to dynamically learn and fuse the differential information of vessel features between the two hemispheres, enhancing the sensitivity of the classification model to occluded vessels. To optimize the feature differential information among similar vessels, we further propose a novel cooperative learning loss function to minimize changes within classes and similarities between classes.Main results.We evaluate our proposed model on an intracranial LVO data set. Compared to state-of-the-art deep learning models, our model performs optimally, achieving a classification sensitivity of 93.73%, precision of 83.33%, accuracy of 89.91% and Macro-F1 score of 87.13%.Significance.This method can adaptively focus on occluded vessel regions and effectively train in scenarios with high inter-class similarity and intra-class variability, thereby improving the performance of LVO classification.

Rapamycin mitigates organ damage by autophagy-mediated NLRP3 inflammasome inactivation in sepsis.

Autophagy activation can alleviate sepsis-induced organ injuries. Rapamycin (Rap) has emerged as an autophagy regulator in multiple forms of organ injuries. This study aimed to assess whether Rap protects rats from cecal ligation and puncture (CLP)-induced sepsis through autophagy-mediated inactivation of the NLRP3 inflammasome. Rats were allocated to the sham, CLP, Rap (10 mg/kg), or 3-Methyladenine (3-MA) (15 mg/kg) groups. A rat CLP model was established. The survival of rats and lung wet-to-dry weight ratio in each group was assessed. Blood biochemical indexes and oxidative stress-related factors were analyzed with an automatic biochemical analyzer. The bacterial counts of blood and organs were monitored. The degrees of myeloperoxidase of the ileum, inflammation-related indexes, and pathological changes in the tissues were detected by ELISA and hematoxylin-eosin staining. The levels of NLRP3 inflammasome and autophagy-related factors were analyzed by Western blot. Rap increased the survival and SOD activity, and repressed ALT, AST, BUN, SCr, MDA, and inflammation-related marker levels in CLP rats, it also restrained the bacterial counts of blood, lung, liver, and kidney in CLP rats; the effects of 3-MA on CLP rats on the above-mentioned indicators were opposite to those of Rap. Additionally, Rap alleviated the pathological injury of the lung, liver, and kidney, which was the opposite to the effect of 3-MA on CLP rats. Furthermore, Rap mitigated the ASC, Pro-caspase 1, and NLRP3 levels and increased the Beclin-1 levels and the LC3II/LC3I ratio in the organ tissues. Collectively, autophagy activation can mitigate organ damage by suppressing the NLRP3 inflammasome in sepsis rats.

E3 ubiquitin ligase Hul6 modulates iron-dependent metabolism by regulating Php4 stability.

Schizosaccharomyces pombe Php4 is the regulatory subunit of the CCAAT-binding complexes and plays an important role in the regulation of iron homeostasis and iron-dependent metabolism. Here, we show that Php4 undergoes ubiquitin-dependent degradation in the late logarithmic and stationary phases. The degradation and ubiquitination of Php4 could be attenuated by deletion of hul6, a gene encoding a putative HECT-type E3 ubiquitin ligase. The expression levels of Hul6 and Php4 are oppositely regulated during cell growth. Hul6 interacts with the C-terminal region of Php4. Two lysine residues (K217 and K274) located in the C-terminal region of Php4 are required for its polyubiquitination. Increasing the levels of Php4 by deletion of hul6 or overexpression of php4 decreased expression of Php4 target proteins involved in iron-dependent metabolic pathways such as the tricarboxylic cycle and mitochondrial oxidative phosphorylation, thus causing increased sensitivity to high-iron and reductions in succinate dehydrogenase and mitochondrial complex II activities. Hul6 is located primarily in the mitochondrial outer membrane and most likely targets cytosolic Php4 for ubiquitination and degradation. Taken together, our data suggest that Hul6 regulates iron-dependent metabolism through degradation of Php4 under normal growth conditions. Our results also suggest that Hul6 promotes iron-dependent metabolism to help the cell to adapt to a nutrient-starved growth phase.

Above-Room-Temperature Ferromagnetism in Copper-Doped Two-Dimensional Chromium-Based Nanosheets.

Two-dimensional ferromagnetic materials (2D-FMs) are expected to become ideal candidates for low-power, high-density information storage in next-generation spintronics devices due to their atomically ultrathin and intriguing magnetic properties. However, 2D-FMs with room-temperature Curie temperatures (Tc) are still rarely reported, which greatly hinders their research progress and practical applications. Herein, ultrathin Cu-doped Cr7Te8 FMs were successfully prepared and can achieve above-room-temperature ferromagnetism with perpendicular magnetic anisotropy via a facile chemical vapor deposition (CVD) method, which can be controlled down to an atomic thin layer of ∼3.4 nm. STEM-EDX quantitative analysis shows that the proportion of Cu to metal atoms is ∼5%. Moreover, based on the anomalous Hall effect (AHE) measurements in a six-terminal Hall bar device without any encapsulation as well as an out-of-plane magnetic field, the maximum Tc achieved ∼315 K when the thickness of the sample is ∼28.8 nm; even the ultrathin 7.6 nm sample possessed a near-room-temperature Tc of ∼275 K. Meanwhile, theoretical calculations elucidated the mechanism of the ferromagnetic enhancement of Cu-doped Cr7Te8 nanosheets. More importantly, the ferromagnetism of CVD-synthesized Cu-doped CrSe nanosheets can also be maintained above room temperature. Our work broadens the scope on room-temperature ferromagnets and their heterojunctions, promoting fundamental research and practical applications in next-generation spintronics.

Infliximab alleviates memory impairment in rats with chronic pain by suppressing neuroinflammation and restoring hippocampal neurogenesis.

Patients with chronic pain commonly report impaired memory. Increasing evidence has demonstrated that inhibition of neurogenesis by neuroinflammation plays a crucial role in chronic pain-associated memory impairments. There is currently a lack of treatment strategies for this condition. An increasing number of clinical trials have reported the therapeutic potential of anti-inflammatory therapies targeting tumour necrosis factor-α (TNF-α) for inflammatory diseases. The present study investigated whether infliximab alleviates chronic pain-associated memory impairments in rats with chronic constriction injury (CCI). We demonstrated that infliximab alleviated spatial memory impairment and hyperalgesia induced by CCI. Furthermore, infliximab inhibited the activation of hippocampal astrocytes and microglia and decreased the release of proinflammatory cytokines in CCI rats. Furthermore, infliximab reversed the decrease in the numbers of newborn neurons and mature neurons in the dentate gyrus (DG) caused by chronic pain. Our data provide evidence that infliximab alleviates chronic pain-associated memory impairments, suppresses neuroinflammation and restores hippocampal neurogenesis in a CCI model. These facts indicate that infliximab may be a potential therapeutic agent for the treatment of chronic pain and associated memory impairments.

3-aminophenylboronic acid modified carbon nitride quantum dots as fluorescent probe for selective detection of dopamine and cell imaging.

Dopamine (DA) is the most abundant catecholamine neurotransmitter in the brain and plays an extremely essential role in the physiological activities of the living organism. There is a critical need for accurately and efficiently detecting DA levels in organisms in order to reflect physiological states. Carbon nitride quantum dots (C3N4) were, in recent years, used enormously as electrochemical and fluorescence probes for the detection of metal ions, biomarkers and other environmental or food impurities due to their unique advantageous optical and electronic properties. 3-Aminophenylboronic acid (3-APBA) can specifically combine with DA through an aggregation effect, providing an effective DA detection method. In this work, 3-APBA modified carbon nitride quantum dots (3-APBA-CNQDs) were synthesized from urea and sodium citrate. The structure, chemical composition and optical properties of 3-APBA-CNQDs were investigated by XRD, TEM, UV-visible, and FT-IR spectroscopy. The addition of DA could induce fluorescence quenching of 3-APBA-CNQDs possibly through the inner filter effect (IFE). 3-APBA-CNQDs shows better selectivity and sensitivity to DA than other interfering substances. By optimizing the experiment conditions, good linearity was obtained at 0.10-51µM DA with a low detection limit of 22.08 nM. More importantly, 3-APBA-CNQDs have been successfully applied for the detection of DA in human urine and blood samples as well as for bioimaging of intracellular DA. This study provides a promising novel method for the rapid detection of DA in real biological samples.

Mechanisms of Heat-Treatment-Induced Cracking in Additively Manufactured IN738 Alloy.

The present study conducts a comprehensive study on heat-treatment-induced cracking of Inconel 738 (IN738) alloy fabricated by laser powder bed fusion (LPBF) using scanning electron microscopy (SEM), energy dispersion spectrum (EDS), and electron backscatter diffraction (EBSD). The results indicate that the macroscopic crack is dominantly triggered by the strain-age cracking mechanism and propagates along grain boundaries. The initiation of cracking is facilitated by the superimposition of residual stress induced by the LPBF process and contraction stress induced by precipitation, while the reopening of compress pores at grain boundaries weakens the grain boundaries and provides fast channels for cracking. These results revealed the coupling effects in triggering heat-treatment-induced cracking, offering a fundamental guideline for crack control during heat treatment of additively manufactured IN738 alloy.

Converging bioprinting and organoids to better recapitulate the tumor microenvironment.

Bioprinting shows excellent potential for preclinical tumor modeling, with significant advantages over 2D cell cultures in replicating the tumor microenvironment (TME). Recently, the use of tumor organoids in bioprinting models has emerged as a groundbreaking approach to simulate volumetric tumor tissues. This synergetic fabrication method leverages the advantages of the spatial and geometric control of bioprinting to assemble heterogeneous TME components, while tumor organoids maintain collective cell behaviors. In this review, we provide a landscape of the latest progress on the convergence of 3D bioprinting and tumor organoids. Furthermore, we discuss the potential to incorporate organ-on-a-chip with bioprinting tumor organoids to improve the biomimicry and predictability of therapeutic performance. Lastly, we address the challenges to personalized medicine and predictive clinical integration.

Ovarian Tumor Domain-Containing 7B Attenuates Pathological Cardiac Hypertrophy by Inhibiting Ubiquitination and Degradation of Krüppel-Like Factor 4.

BACKGROUND: Cardiac hypertrophy (CH) is a well-established risk factor for many cardiovascular diseases and a primary cause of mortality and morbidity among older adults. Currently, no pharmacological interventions have been specifically tailored to treat CH. OTUD7B (ovarian tumor domain-containing 7B) is a member of the ovarian tumor-related protease (OTU) family that regulates many important cell signaling pathways. However, the role of OTUD7B in the development of CH is unclear. Therefore, we investigated the role of OTUD7B in CH. METHODS AND RESULTS: OTUD7B knockout mice were used to assay the role of OTUD7B in CH after transverse aortic coarctation surgery. We further assayed the specific functions of OTUD7B in isolated neonatal rat cardiomyocytes. We found that OTUD7B expression decreased in hypertrophic mice hearts and phenylephrine-stimulated neonatal rat cardiomyocytes. Furthermore, OTUD7B deficiency exacerbated transverse aortic coarctation surgery-induced myocardial hypertrophy, abnormal cardiac function, and fibrosis. In cardiac myocytes, OTUD7B knockdown promoted phenylephrine stimulation-induced myocardial hypertrophy, whereas OTUD7B overexpression had the opposite effect. An immunoprecipitation-mass spectrometry analysis showed that OTUD7B directly binds to KLF4 (Krüppel-like factor 4). Additional molecular experiments showed that OTUD7B impedes KLF4 degradation by inhibiting lysine residue at 48 site-linked ubiquitination and suppressing myocardial hypertrophy by activating the serine/threonine kinase pathway. CONCLUSIONS: These results demonstrate that the OTUD7B-KLF4 axis is a novel molecular target for CH treatment.

Efficacy of various surgical approaches in treating hematospermia using transurethral seminal vesiculoscopy.

PURPOSE: To explore the efficacy of different approaches of seminal vesiculoscopy surgery and the predictive factors of good treatment outcome. MATERIALS AND METHODS: A retrospective analysis of 68 patients who underwent seminal vesiculoscopy for hematospermia in our hospital from January 2015 to January 2021. According to different surgical approaches, they were divided into three groups: natural ejaculatory ducts (method A, 45 cases), assisted transurethral resection/incision of ejaculatory ducts (method B, 14 cases), fenestration in prostatic utricle (method C, 9 cases). We analyzed the recurrence rate of the three surgical approaches and the predictive factors of treatment efficacy. RESULTS: The total recurrence rate after the seminal vesiculoscopy for hematospermia in this group was 32.35%. The postoperative recurrence rates of the three methods were 24.44% for method A, 50.00% for method B and 44.44% for method C, and there was no significant difference among the three methods (P > 0.05). The data of five predictors of 45 cases in method A group were included in the Univariate Logistic analysis, the results suggest that whether complicated with seminal tract stones/cysts was an effective predictor (OR 0.250, P = 0.022), which was still an effective predictor in the Multivariate Logistic analysis model (OR 0.244, P = 0.010). CONCLUSIONS: The Transurethral seminal vesiculoscopy technique demonstrates a low postoperative recurrence rate in treating hematospermia. Among the various approaches, the intraoperative use of natural orifices through the ejaculatory duct exhibits the lowest recurrence rate. Additionally, seminal tract stones/cysts effectively predict favorable postoperative outcomes.

Neuroprotective Bioorthogonal Catalysis in Mitochondria Using Protein-Integrated Hydrogen-Bonded Organic Frameworks.

Mitochondria-targeted bioorthogonal catalysis holds promise for controlling cell function precisely, yet achieving selective and efficient chemical reactions within organelles is challenging. In this study, we introduce a new strategy using protein-integrated hydrogen-bonded organic frameworks (HOFs) to enable synergistic bioorthogonal chemical catalysis and enzymatic catalysis within mitochondria. Utilizing catalytically active tris(4,4'-dicarboxylicacid-2,2'-bipyridyl) ruthenium(II) to self-assemble with [1,1'-biphenyl]-4,4'-biscarboximidamide, we synthesized nanoscale RuB-HOFs that exhibit high photocatalytic reduction activity. Notably, RuB-HOFs efficiently enter cells and preferentially localize to mitochondria, where they facilitate bioorthogonal photoreduction reactions. Moreover, we show that RuB-HOFs encapsulating catalase can produce hydrogen sulfide (H2 S) in mitochondria through photocatalytic reduction of pro-H2 S and degrade hydrogen peroxide through enzymatic catalysis simultaneously, offering a significant neuroprotective effect against oxidative stress. Our findings not only introduce a versatile chemical toolset for mitochondria-targeted bioorthogonal catalysis for prodrug activation but also pave the way for potential therapeutic applications in treating diseases related to cellular oxidative stress.