Anxiety and sleep quality in patients receiving maintenance hemodialysis: multiple mediating roles of hope and family function.

The objective of this cross-sectional study was to examine the extent of sleep quality among individuals undergoing maintenance hemodialysis (MHD) and to scrutinize whether hope and family function serve as mediators in the association between anxiety and sleep quality in this cohort. A convenience sampling method was used to recruit 227 patients receiving maintenance hemodialysis from two tertiary hospitals in Wuhan. Participants completed several self-report questionnaires, including the Sociodemographic questionnaire, Hospital Anxiety and Depression Scale, Athens Insomnia Scale, Herth Hope Index, and Family APGAR Index. As per the findings of the chain mediation analysis, it was observed that the sleep quality scores were directly predicted by anxiety. Moreover, anxiety positively predicted sleep quality scores through hope and family function as mediators. The observed types of mediation were partial mediation. The total indirect effect value was 0.354, indicating the mediating effect of hope and family function, while the total effect value was 0.481, representing the overall effect of anxiety on sleep quality. The total effect size was 73.60% (0.354/0.481), indicating that the mediation accounted for a significant portion of the relationship. This study established the chain mediating effect of hope and family function between anxiety and sleep quality in patients receiving maintenance hemodialysis. The findings highlight the importance of addressing anxiety and promoting hope and family function to improve sleep quality in this population. The findings suggest that healthcare professionals should be attentive to the anxiety levels of these patients and implement targeted interventions to help alleviate anxiety, enhance hope, and improve family functioning, with the ultimate goal of improving sleep quality in this population.

Systemic delivery of oncolytic herpes virus using CAR-T cells enhances targeting of antitumor immuno-virotherapy.

Recent studies have indicated that combining oncolytic viruses with CAR-T cells in therapy has shown superior anti-tumor effects, representing a promising approach. Nonetheless, the localized delivery method of intratumoral injection poses challenges for treating metastatic tumors or distal tumors that are difficult to reach. To address this obstacle, we employed HSV-1-infected CAR-T cells, which systemically delivery HSV into solid tumors. The biological function of CAR-T cells remained intact after loading them with HSV for a period of three days. In both immunocompromised and immunocompetent GBM orthotopic mouse models, B7-H3 CAR-T cells effectively delivered HSV to tumor lesions, resulting in enhanced T-cell infiltration and significantly prolonged survival in mice. We also employed a bilateral subcutaneous tumor model and observed that the group receiving intratumoral virus injection exhibited a significant reduction in tumor volume on the injected side, while the group receiving intravenous infusion of CAR-T cells carrying HSV displayed suppressed tumor growth on both sides. Hence, CAR-THSV cells offer notable advantages in the systemic delivery of HSV to distant tumors. In conclusion, our findings emphasize the potential of CAR-T cells as carriers for HSV, presenting significant advantages for oncolytic virotherapy targeting distant tumors.

A Novel Nano-Laminated GdB2C2 with Excellent Electromagnetic Wave Absorption Performance and Ultra-High-Temperature Thermostability.

A novel nano-laminated GdB2C2 material was successfully synthesized using GdH2, B4C, and C via an in situ solid-state reaction approach for the first time. The formation process of GdB2C2 was revealed based on the microstructure and phase evolution investigation. Purity of 96.4 wt.% GdB2C2 was obtained at a low temperature of 1500 °C, while a nearly fully pure GdB2C2 could be obtained at a temperature over 1700 °C. The as-obtained GdB2C2 presented excellent thermal stability at a high temperature of 2100 °C in Ar atmosphere due to the stable framework formed by the high-covalence four-member and eight-member B-C rings in GdB2C2. The GdB2C2 material synthesized at 1500 °C demonstrated a remarkably low minimum reflection loss (RLmin) of -47.01 dB (3.44 mm) and a broad effective absorption bandwidth (EAB) of 1.76 GHz. The possible electromagnetic wave absorption (EMWA) mechanism could be ascribed to the nano-laminated structure and appropriate electrical conductivity, which facilitated good impedance matching, remarkable conduction loss, and interfacial polarization, along with the reflection and scattering of electromagnetic waves at multiple interfaces. The GdB2C2, with excellent EMWA performance as well as remarkable ultra-high-temperature thermal stability, could be a promising candidate for the application of EMWA materials in extreme ultra-high temperatures.

Bailout intracranial angioplasty or stenting following thrombectomy for acute large vessel occlusion in China (ANGEL-REBOOT): a multicentre, open-label, blinded-endpoint, randomised controlled trial.

BACKGROUND: Unsuccessful recanalisation or reocclusion after thrombectomy is associated with poor outcomes in patients with large vessel occlusion (LVO) acute ischaemic stroke (LVO-AIS). Bailout angioplasty or stenting (BAOS) could represent a promising treatment for these patients. We conducted a randomised controlled trial with the aim to investigate the safety and efficacy of BAOS following thrombectomy in patients with LVO. METHODS: ANGEL-REBOOT was an investigator-initiated, multicentre, prospective, randomised, controlled, open-label, blinded-endpoint clinical trial conducted at 36 tertiary hospitals in 19 provinces in China. Participants with LVO-AIS 24 h after symptom onset were eligible if they had unsuccessful recanalisation (expanded Thrombolysis In Cerebral Infarction score of 0-2a) or risk of reocclusion (residual stenosis >70%) after thrombectomy. Eligible patients were randomly assigned by the minimisation method in a 1:1 ratio to undergo BAOS as the intervention treatment, or to receive standard therapy (continue or terminate the thrombectomy procedure) as a control group, both open-label. In both treatment groups, tirofiban could be recommended for use during and after the procedure. The primary outcome was the change in modified Rankin Scale score at 90 days, assessed in the intention-to-treat population. Safety outcomes were compared between groups. This trial was completed and registered at ClinicalTrials.gov (NCT05122286). FINDINGS: From Dec 19, 2021, to March 17, 2023, 706 patients were screened, and 348 were enrolled, with 176 assigned to the intervention group and 172 to the control group. No patients withdrew from the trial or were lost to follow-up for the primary outcome. The median age of patients was 63 years (IQR 55-69), 258 patients (74%) were male, and 90 patients (26%) were female; all participants were Chinese. After random allocation, tirofiban was administered either intra-arterially, intravenously, or both in 334 [96%] of 348 participants. No between-group differences were observed in the primary outcome (common odds ratio 0·86 [95% CI 0·59-1·24], p=0·41). Mortality was similar between the two groups (19 [11%] of 176 vs 17 [10%] of 172), but the intervention group showed a higher risk of symptomatic intracranial haemorrhage (eight [5%] of 175 vs one [1%] of 169), parenchymal haemorrhage type 2 (six [3%] of 175 vs none in the control group), and procedure-related arterial dissection (24 [14%] of 176 vs five [3%] of 172). INTERPRETATION: Among Chinese patients with unsuccessful recanalisation or who are at risk of reocclusion after thrombectomy, BAOS did not improve clinical outcome at 90 days, and incurred more complications compared with standard therapy. The off-label use of tirofiban might have affected our results and their generalisability, but our findings do not support the addition of BAOS for such patients with LVO-AIS. FUNDING: Beijing Natural Science Foundation, National Natural Science Foundation of China, National Key R&D Program Beijing Municipal Administration of Hospitals Incubating Program, Shanghai HeartCare Medical Technology, HeMo (China) Bioengineering, Sino Medical Sciences Technology.

Bacterial adhesion and corrosion behavior of different pure metals induced by sulfate reducing bacteria.

The corrosion behaviors of four pure metals (Fe, Ni, Mo and Cr) in the presence of sulfate reducing bacteria (SRB) were investigated in enriched artificial seawater (EASW) after 14-day incubation. Metal Fe and metal Ni experienced weight losses of 1.96 mg cm-2 and 1.26 mg cm-2, respectively. In contrast, metal Mo and metal Cr exhibited minimal weight losses, with values of only 0.05 mg cm-2 and 0.03 mg cm-2, respectively. In comparison to Mo (2.2 × 106 cells cm-2) or Cr (1.4 × 106 cells cm-2) surface, the sessile cell counts on Fe (4.0 × 107 cells cm-2) or Ni (3.1 × 107 cells cm-2) surface was higher.

NIR-Driven Self-Healing Phase-Change Solid Slippery Surface with Stability and Promising Antifouling and Anticorrosion Properties.

Slippery liquid-infused porous surfaces (SLIPSs) have great potential to replace traditional antifouling coatings due to their efficient, green, and broad-spectrum antifouling performance. However, the lubricant dissipation problem of SLIPS severely restricts its further development and application, and the robust SLIPS continues to be extremely challenging. Here, a composite phase-change lubricant layer consisting of paraffin, silicone oil, and MXene is designed to readily construct a stable and NIR-responsive self-healing phase-change solid slippery surface (PCSSS). Collective results showed that PCSSS could rapidly achieve phase-change transformation and complete self-healing under NIR irradiation and keep stable after high-speed water flushing, centrifugation, and ultrasonic treatment. The antifouling performance of PCSSS evaluated by protein, bacteria, and algae antiadhesion tests demonstrated the adhesion inhibition rate was as high as 99.99%. Moreover, the EIS and potentiodynamic polarization experiments indicated that PCSSS had stable and exceptional corrosion resistance (|Z|0.01Hz = 3.87 × 108 Ω·cm2) and could effectively inhibit microbiologically influenced corrosion. The 90 day actual marine test reveals that PCSSS has remarkable antifouling performance. Therefore, PCSSS presents a novel, facile, and effective strategy to construct a slippery surface with the prospect of facilitating its application in marine antifouling and corrosion protection.

A feedback loop driven by H3K9 lactylation and HDAC2 in endothelial cells regulates VEGF-induced angiogenesis.

BACKGROUND: Vascular endothelial growth factor (VEGF) is one of the most powerful proangiogenic factors and plays an important role in multiple diseases. Increased glycolytic rates and lactate accumulation are associated with pathological angiogenesis. RESULTS: Here, we show that a feedback loop between H3K9 lactylation (H3K9la) and histone deacetylase 2 (HDAC2) in endothelial cells drives VEGF-induced angiogenesis. We find that the H3K9la levels are upregulated in endothelial cells in response to VEGF stimulation. Pharmacological inhibition of glycolysis decreases H3K9 lactylation and attenuates neovascularization. CUT& Tag analysis reveals that H3K9la is enriched at the promoters of a set of angiogenic genes and promotes their transcription. Interestingly, we find that hyperlactylation of H3K9 inhibits expression of the lactylation eraser HDAC2, whereas overexpression of HDAC2 decreases H3K9 lactylation and suppresses angiogenesis. CONCLUSIONS: Collectively, our study illustrates that H3K9la is important for VEGF-induced angiogenesis, and interruption of the H3K9la/HDAC2 feedback loop may represent a novel therapeutic method for treating pathological neovascularization.

The role of JMJD2A in immune evasion and malignant behavior of esophageal squamous cell carcinoma.

OBJECTIVE: This study aimed to investigate the role of JMJD2A in radiotherapy tolerance of esophageal squamous cell carcinoma (ESCC). METHODS: The levels of H3K9me3 modification were analyzed in anti-PD-1 therapy non-responder or responder patients, and the expression differences of H3K9me3-related modifying enzymes were assessed in TCGA-ESCC and ICGC cohorts. Subsequently, JMJD2A was knocked down in ESCC cells using CRISPR-Cas9 or lentivirus-mediated shRNA, and changes in malignant behavior of ESCC cells were observed. RNA-seq, ATAC-seq, and ChIP-seq analyses were then conducted to investigate the genes and downstream signaling pathways regulated by JMJD2A, and functional validation experiments were performed to analyze the role of downstream regulated genes and pathways in ESCC malignant behavior and immune evasion. RESULTS: JMJD2A was significantly overexpressed in ESCC and anti-PD-1 therapy non-responders. Knockdown or deletion of JMJD2A significantly promoted the malignant behavior and immune evasion of ESCC. JMJD2A facilitated the structural changes in chromatin and promoted the binding of SMARCA4 to super-enhancers, thereby inducing the expression of GPX4. This resulted in the inhibition of radiation-induced DNA damage and cell ferroptosis, ultimately promoting the malignant behavior and immune evasion of ESCC cells. CONCLUSION: JMJD2A plays an indispensable role in the malignant behavior and immune evasion of ESCC. It regulates the binding of SMARCA4 to super-enhancers and affects the chromatin's epigenetic landscape, thereby promoting the expression of GPX4 and attenuating iron-mediated cell death caused by radiotherapy. Consequently, it triggers the malignant behavior and immune evasion of ESCC cells.

Orally available dextran-aspirin nanomedicine modulates gut inflammation and microbiota homeostasis for primary colorectal cancer therapy.

Reversing the aggravated immunosuppression hence overgrowth of colorectal cancer (CRC) caused by the gut inflammation and microbiota dysbiosis is pivotal for effective CRC therapy and metastasis inhibition. However, the low delivery efficiency and severe dose-limiting off-target toxicities caused by unsatisfied drug delivery systems remain the major obstacles in precisely modulating gut inflammation and microbiota in CRC therapy. Herein, a multifunctional oral dextran-aspirin nanomedicine (P3C-Asp) was utilized for oral treatment of primary CRC, as it could release salicylic acid (SA) while scavenging reactive oxygen species (ROS) and held great potential in modulating gut microbiota with prebiotic (dextran). Oral P3C-Asp retained in CRC tissues for over 12 h and significantly increased SA accumulation in CRC tissues over free aspirin (10.8-fold at 24 h). The enhanced SA accumulation and ROS scavenging of P3C-Asp cooperatively induced more potent inflammation relief over free aspirin, characterized as lower level of cyclooxygenase-2 and immunosuppressive cytokines. Remarkably, P3C-Asp promoted the microbiota homeostasis and notably increased the relative abundance of strengthening systemic anti-cancer immune response associated microbiota, especially lactobacillus and Akkermansia to 6.66- and 103- fold over the control group. Additionally, a demonstrable reduction in pathogens associated microbiota (among 96% to 79%) including Bacteroides could be detected. In line with our findings, inflammation relief along with enhanced abundance of lactobacillus was positively correlated with CRC inhibition. In primary CRC model, P3C-Asp achieved 2.1-fold tumor suppression rate over free aspirin, with an overall tumor suppression rate of 85%. Moreover, P3C-Asp cooperated with αPD-L1 further reduced the tumor weight of each mouse and extended the median survival of mice by 29 days over αPD-L1 alone. This study unravels the synergistic effect of gut inflammation and microbiota modulation in primary CRC treatment, and unlocks an unconventional route for immune regulation in TME with oral nanomedicine.

Ankylosing spondylitis prediction using fuzzy K-nearest neighbor classifier assisted by modified JAYA optimizer.

The diagnosis of ankylosing spondylitis (AS) can be complex, necessitating a comprehensive assessment of medical history, clinical symptoms, and radiological evidence. This multidimensional approach can exacerbate the clinical burden and increase the likelihood of diagnostic inaccuracies, which may result in delayed or overlooked cases. Consequently, supplementary diagnostic techniques for AS have become a focal point in clinical research. This study introduces an enhanced optimization algorithm, SCJAYA, which incorporates salp swarm foraging behavior with cooperative predation strategies into the JAYA algorithm framework, noted for its robust optimization capabilities that emulate the evolutionary dynamics of biological organisms. The integration of salp swarm behavior is aimed at accelerating the convergence speed and enhancing the quality of solutions of the classical JAYA algorithm while the cooperative predation strategy is incorporated to mitigate the risk of convergence on local optima. SCJAYA has been evaluated across 30 benchmark functions from the CEC2014 suite against 9 conventional meta-heuristic algorithms as well as 9 state-of-the-art meta-heuristic counterparts. The comparative analyses indicate that SCJAYA surpasses these algorithms in terms of convergence speed and solution precision. Furthermore, we proposed the bSCJAYA-FKNN classifier: an advanced model applying the binary version of SCJAYA for feature selection, with the aim of improving the accuracy in diagnosing and prognosticating AS. The efficacy of the bSCJAYA-FKNN model was substantiated through validation on 11 UCI public datasets in addition to an AS-specific dataset. The model exhibited superior performance metrics-achieving an accuracy rate, specificity, Matthews correlation coefficient (MCC), F-measure, and computational time of 99.23 %, 99.52 %, 0.9906, 99.41 %, and 7.2800 s, respectively. These results not only underscore its profound capability in classification but also its substantial promise for the efficient diagnosis and prognosis of AS.

Icariin alleviates oxygen-induced retinopathy by targeting microglia hexokinase 2.

Retinopathy of prematurity (ROP) is a retinal disease-causing retinal neovascularization that can lead to blindness. Oxygen-induced retinopathy (OIR) is a widely used ROP animal model. Icariin (ICA) has anti-oxidative and anti-inflammation properties; however, whether ICA has a regulatory effect on OIR remains unclear. In this study, ICA alleviated pathological neovascularization, microglial activation and blood-retina barrier (BRB) damage in vivo. Further results indicated that endothelial cell tube formation, migration and proliferation were restored by ICA treatment in vitro. Proteomic microarrays and molecular mimicry revealed that ICA can directly bind to hexokinase 2 (HK2) and decrease HK2 protein expression in vivo and in vitro. In addition, ICA inhibited the AKT/mTOR/HIF1α pathway activation. The effects of ICA on pathological neovascularization, microglial activation and BRB damage disappeared after HK2 overexpression in vivo. Similarly, the endothelial cell function was revised after HK2 overexpression. HK2 overexpression reversed ICA-induced AKT/mTOR/HIF1α pathway inhibition in vivo and in vitro. Therefore, ICA prevented pathological angiogenesis in OIR in an HK2-dependent manner, implicating ICA as a potential therapeutic agent for ROP.

Shining light on carbon dots: Toward enhanced antibacterial activity for biofilm disruption.

In spite of tremendous efforts dedicated to addressing bacterial infections and biofilm formation, the post-antibiotic ear continues to witness a gap between the established materials and an easily accessible yet biocompatible antibacterial reagent. Here we show carbon dots (CDs) synthesized via a single hydrothermal process can afford promising antibacterial activity that can be further enhanced by exposure to light. By using citric acid and polyethyleneimine as the precursors, the photoluminescence CDs can be produced within a one-pot, one-step hydrothermal reaction in only 2 h. The CDs demonstrate robust antibacterial properties against both Gram-positive and Gram-negative bacteria and, notably, a considerable enhancement of antibacterial effect can be observed upon photo-irradiation. Mechanistic insights reveal that the CDs generate singlet oxygen (1O2) when exposed to light, leading to an augmented reactive oxygen species level. The approach for disruption of biofilms and inhibition of biofilm formation by using the CDs has also been established. Our findings present a potential solution to combat antibacterial resistance and offer a path to reduce dependence on traditional antibiotics.

Naked-Eye LAMP Assay of M. tuberculosis in Sputum by In Situ Au Nanoprobe Identification: For the In Vitro Diagnostics of Tuberculosis.

In spite of the development of diagnostic tests for Mycobacterium tuberculosis (M. tuberculosis), the etiological agent of tuberculosis, there has remained a gap between the established methods and an easily accessible diagnostic test, particularly in developing and resource-poor areas. By combining isothermal amplification of IS6110 as the target gene and recognition by DNA-functionalized Au nanoparticles (DNA-AuNPs), we develop a colorimetric LAMP assay for convenient in vitro diagnostics of tuberculosis with a quick (≤50 min) "yes" or "no" readout. The DNA-AuNPs not only tolerate the interference in the complex LAMP system but also afford in situ identification of the amplicon, allowing for colloidal dispersion via steric effect depending on DNA grafting density. The target-induced stabilization and red appearance of the DNA-AuNPs contrast with the occurrence of gray aggregates in a negative sample. Furthermore, the DNA-AuNPs demonstrate excellent performance after long-term (≥7 months) storage while preserving the unsacrificed sensitivity. The high specificity of the DNA-AuNPs is further demonstrated in the naked-eye LAMP assay of M. tuberculosis in patients' sputum samples. Given the rapidity, cost-effectiveness, and instrument-free characteristics, the naked-eye LAMP assay is particularly beneficial for tuberculosis diagnosis in urgent situations and resource-limited settings and can potentially expedite patient care and treatment initiation.

Single­cell RNA sequencing reveals inflammatory retinal microglia in experimental autoimmune uveitis.

Autoimmune uveitis (AU) is a kind of immune-mediated disease resulting in irreversible ocular damage and even permanent vision loss. However, the precise mechanism underlying dynamic immune changes contributing to disease initiation and progression of AU remains unclear. Here, we induced an experimental AU (EAU) model with IRBP651-670 and found that day[D]14 was the inflammatory summit with remarking clinical and histopathological manifestations and the activation of retinal microglia exhibited a time-dependent pattern in the EAU course. We conducted single-cell RNA sequencing of retinal immune cells in EAU mice at four time points and found microglia constituting the largest proportion, especially on D14. A novel inflammatory subtype (Cd74high Ccl5high) of retinal microglia was identified at the disease peak that was closely associated with modulating immune responses. In vitro experiments indicated that inflammatory stimuli induced proinflammatory microglia with the upregulation of CD74 and CCL5, and CD74 overexpression in microglia elicited their proinflammatory phenotype via nuclear factor-kappa B signaling that could be attenuated by the treatment of neutralizing CCL5 antibody to a certain extent. In-vivo blockade of Cd74 and Ccl5 effectively alleviated retinal microglial activation and disease phenotype of EAU. Therefore, we propose targeting CD74 and CCL5 of retinal microglia as promising strategies for AU treatment.

Janus MXene nanosheets with a strain-induced reversible magnetic state transition for storing information without electricity.

The application of strain induces a transition in the ground-state magnetic configuration of Janus TiVC MXene from A-AFM to FM. A new system and method of solid-state disk information storage without electricity is developed based on the as-discovered reversible magnetic state transition in TiVC, which can achieve efficient storage of information in extremely harsh conditions.

Geometric Matching for Cross-Modal Retrieval.

Despite its significant progress, cross-modal retrieval still suffers from one-to-many matching cases, where the multiplicity of semantic instances in another modality could be acquired by a given query. However, existing approaches usually map heterogeneous data into the learned space as deterministic point vectors. In spite of their remarkable performance in matching the most similar instance, such deterministic point embedding suffers from the insufficient representation of rich semantics in one-to-many correspondence. To address the limitations, we intuitively extend a deterministic point into a closed geometry and develop geometric representation learning methods for cross-modal retrieval. Thus, a set of points inside such a geometry could be semantically related to many candidates, and we could effectively capture the semantic uncertainty. We then introduce two types of geometric matching for one-to-many correspondence, i.e., point-to-rectangle matching (dubbed P2RM) and rectangle-to-rectangle matching (termed R2RM). The former treats all retrieved candidates as rectangles with zero volume (equivalent to points) and the query as a box, while the latter encodes all heterogeneous data into rectangles. Therefore, we could evaluate semantic similarity among heterogeneous data by the Euclidean distance from a point to a rectangle or the volume of intersection between two rectangles. Additionally, both strategies could be easily employed for off-the-self approaches and further improve the retrieval performance of baselines. Under various evaluation metrics, extensive experiments and ablation studies on several commonly used datasets, two for image-text matching and two for video-text retrieval, demonstrate our effectiveness and superiority.

Error Compensation Method for Pedestrian Navigation System Based on Low-Cost Inertial Sensor Array.

In the pedestrian navigation system, researchers have reduced measurement errors and improved system navigation performance by fusing measurements from multiple low-cost inertial measurement unit (IMU) arrays. Unfortunately, the current data fusion methods for inertial sensor arrays ignore the system error compensation of individual IMUs and the correction of position information in the zero-velocity interval. Therefore, these methods cannot effectively reduce errors and improve accuracy. An error compensation method for pedestrian navigation systems based on a low-cost array of IMUs is proposed in this paper. The calibration method for multiple location-free IMUs is improved by using a sliding variance detector to segment the angular velocity magnitude into stationary and motion intervals, and each IMU is calibrated independently. Compensation is then applied to the velocity residuals in the zero-velocity interval after zero-velocity update (ZUPT). The experimental results show a significant improvement in the average noise performance of the calibrated IMU array, with a 3.01-fold increase in static noise performance. In the closed-loop walking experiment, the average horizontal position error of a single calibrated IMU is reduced by 27.52% compared to the uncalibrated IMU, while the calibrated IMU array shows a 2.98-fold reduction in average horizontal position error compared to a single calibrated IMU. After compensating for residual velocity, the average horizontal position error of a single IMU is reduced by 0.73 m, while that of the IMU array is reduced by 64.52%.

Exponentially Enhanced Non-Hermitian Cooling.

Certain non-Hermitian systems exhibit the skin effect, whereby the wave functions become exponentially localized at one edge of the system. Such exponential amplification of wavefunction has received significant attention due to its potential applications in, e.g., classical and quantum sensing. However, the opposite edge of the system, featured by exponentially suppressed wave functions, remains largely unexplored. Leveraging this phenomenon, we introduce a non-Hermitian cooling mechanism, which is fundamentally distinct from traditional refrigeration or laser cooling techniques. Notably, non-Hermiticity will not amplify thermal excitations, but rather redistribute them. Hence, thermal excitations can be cooled down at one edge of the system, and the cooling effect can be exponentially enhanced by the number of auxiliary modes, albeit with a lower bound that depends on the dissipative interaction with the environment. Non-Hermitian cooling does not rely on intricate properties such as exceptional points or nontrivial topology, and it can apply to a wide range of excitations.

Melatonin alleviates oxidative stress damage in mouse testes induced by bisphenol A.

We investigated the effect of melatonin on bisphenol A (BPA)-induced oxidative stress damage in testicular tissue and Leydig cells. Mice were gavaged with 50 mg/kg BPA for 30 days, and concurrently, were injected with melatonin (10 mg/kg and 20 mg/kg). Leydig cells were treated with 10 µmol/L of BPA and melatonin. The morphology and organ index of the testis and epididymis were observed and calculated. The sperm viability and density were determined. The expressions of melatonin receptor 1A and luteinizing hormone receptor, and the levels of malonaldehyde, antioxidant enzymes, glutathione, steroid hormone synthases, aromatase, luteinizing hormone, testosterone, and estradiol were measured. TUNEL assay was utilized to detect testicular cell apoptosis. The administration of melatonin at 20 mg/kg significantly improved the testicular index and epididymis index in mice treated with BPA. Additionally, melatonin promoted the development of seminiferous tubules in the testes. Furthermore, the treatment with 20 mg/kg melatonin significantly increased sperm viability and sperm density in mice, while also promoting the expressions of melatonin receptor 1A and luteinizing hormone receptor in Leydig cells of BPA-treated mice. Significantly, melatonin reduced the level of malonaldehyde in testicular tissue and increased the expression of antioxidant enzymes (superoxide dismutase 1, superoxide dismutase 2, and catalase) as well as the content of glutathione. Moreover, melatonin also reduced the number of apoptotic Leydig cells and spermatogonia, aromatase expression, and estradiol level, while increasing the expression of steroid hormone synthases (steroidogenic acute regulatory protein, cytochrome P450 family 17a1, cytochrome P450 17α-hydroxylase/20-lyase, and, 17ß-hydroxysteroid dehydrogenase) and the level of testosterone. Melatonin exhibited significant potential in alleviating testicular oxidative stress damage caused by BPA. These beneficial effects may be attributed to melatonin's ability to enhance the antioxidant capacity of testicular tissue, promote testosterone synthesis, and reduce testicular cell apoptosis.

Improved antitumor effects elicited by an oncolytic HSV-1 expressing a novel B7H3nb/CD3 BsAb.

Oncolytic viruses have emerged as a promising modality for cancer treatment due to their unique abilities to directly destroy tumor cells and modulate the tumor microenvironment. Bispecific T-cell engagers (BsAbs) have been developed to activate and redirect cytotoxic T lymphocytes, enhancing the antitumor response. To take advantage of the specific infection capacity and carrying ability of exogenous genes, we generated a recombinant herpes simplex virus type 1 (HSV-1), HSV-1dko-B7H3nb/CD3 or HSV-1dko-B7H3nb/mCD3, carrying a B7H3nb/CD3 or B7H3nb/mCD3 BsAb that replicates and expresses BsAb in tumor cells in vitro and in vivo. The new generation of oncolytic viruses has been genetically modified using CRISPR/Cas9 technology and the cre-loxp system to increase the efficiency of HSV genome editing. Additionally, we used two fully immunocompetent models (GL261 and MC38) to assess the antitumor effect of HSV-1dko-B7H3nb/mCD3. Compared with the HSV-1dko control virus, HSV-1dko-B7H3nb/mCD3 induced enhanced anti-tumor immune responses and T-cell infiltration in both GL261 and MC38 models, resulting in improved treatment efficacy in the latter. Furthermore, flow cytometry analysis of the tumor microenvironment confirmed an increase in NK cells and effector CD8+ T cells, and a decrease in immunosuppressive cells, including FOXP3+ regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and CD206+ macrophages (M2). Overall, our study identified a novel camel B7H3 nanobody and described the genetic modification of the HSV-1 genome using CRISPR/Cas9 technology and the cre-loxp system. Our findings indicate that expressing B7H3nb/CD3 BsAb could improve the antitumor effects of HSV-1 based oncolytic virus.