Theabrownin as a Potential Prebiotic Compound Regulates Lipid Metabolism via the Gut Microbiota, Microbiota-Derived Metabolites, and Hepatic FoxO/PPAR Signaling Pathways.

The dysregulation of lipid metabolism poses a significant health threat, necessitating immediate dietary intervention. Our previous research unveiled the prebiotic-like properties of theabrownin. This study aimed to further investigate the theabrownin-gut microbiota interactions and their downstream effects on lipid metabolism using integrated physiological, genomic, metabolomic, and transcriptomic approaches. The results demonstrated that theabrownin significantly ameliorated dyslipidemia, hepatic steatosis, and systemic inflammation induced by a high-fat/high-cholesterol diet (HFD). Moreover, theabrownin significantly improved HFD-induced gut microbiota dysbiosis and induced significant alterations in microbiota-derived metabolites. Additionally, the detailed interplay between theabrownin and gut microbiota was revealed. Analysis of hepatic transcriptome indicated that FoxO and PPAR signaling pathways played pivotal roles in response to theabrownin-gut microbiota interactions, primarily through upregulating hepatic Foxo1, Prkaa1, Pck1, Cdkn1a, Bcl6, Klf2, Ppara, and Pparg, while downregulating Ccnb1, Ccnb2, Fabp3, and Plin1. These findings underscored the critical role of gut-liver axis in theabrownin-mediated improvements in lipid metabolism disorders and supported the potential of theabrownin as an effective prebiotic compound for targeted regulation of metabolic diseases.

Efficacy of electro-acupuncture versus sham acupuncture for diabetic peripheral neuropathy: study protocol for a three-armed randomised controlled trial.

INTRODUCTION: Specific treatment for diabetic peripheral neuropathy (DPN) is still lacking, and acupuncture may relieve the symptoms. We intend to investigate the efficacy and safety of electro-acupuncture (EA) in alleviating symptoms associated with DPN in diabetes. METHODS AND ANALYSIS: This multicentre, three-armed, participant- and assessor-blind, randomised, sham-controlled trial will recruit 240 eligible participants from four hospitals in China and will randomly assign (1:1:1) them to EA, sham acupuncture (SA) or usual care (UC) group. Participants in the EA and SA groups willl receive either 24-session EA or SA treatment over 8 weeks, followed by an 8-week follow-up period, while participants in the UC group will be followed up for 16 weeks. The primary outcome of this trial is the change in DPN symptoms from baseline to week 8, as rated by using the Total Symptom Score. The scale assesses four symptoms: pain, burning, paraesthesia and numbness, by evaluating the frequency and severity of each. All results will be analysed with the intention-to-treat population. ETHICS AND DISSEMINATION: The protocol has been approved by the Ethics Committee of the Beijing University of Chinese Medicine (Identifier: 2022BZYLL0509). Every participant will be informed of detailed information about the study before signing informed consent. The results of this trial will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2200061408.

A Novel growth guidance system for early onset scoliosis: a preliminary in vitro study.

PURPOSE: The purpose of the study was to describe a novel growth guidance system, which can avoid metal debris and reduce the sliding friction forces, and test the durability and glidability of the system by in vitro test. METHOD: Two major modifications were made to the traditional Shilla system, including the use of ultra-high molecular weight polyethylene (UHMWPE) gaskets to avoid direct contact between the screw and rod, and polishing the surface of the sliding part of the rod. We tested the durability of the system by a fatigue test, which the samples were test on the MTS system for a 10 million cycle of a constant displacement. Pre and post-testing involved weighing the UHMWPE gaskets and observing the wear conditions. The sliding ability were measured by a sliding displacement test. The maximum sliding displacement of the system was measured after a 300 cycles of dynamic compressive loads in a sinusoidal waveform. RESULTS: After the fatigue test, all the UHMWPE gaskets samples showed some of the fretting on the edge of the inner sides, but its still isolated and avoided the friction between the screws and rods. There was no production of metallic fretting around the sliding screws and rods. The average wear mass of the UHMWPE gaskets was 0.002 ± 0.001 g, less than 1.7% of the original mass. In the sliding test, the novel growth guidance system demonstrated the best sliding ability, with an average maximum sliding distance(AMSD) of 35.75 ± 5.73 mm, significantly better than the group of the traditional Shilla technique(AMSD 3.65 ± 0.46 mm, P < 0.0001). CONCLUSION: In conclusion, we modified the Shilla technique and designed a novel growth guidance system by changing the friction interface of sliding screw and rod, which may significantly reduce the metallic debris and promote spine growth. The fatigue test and sliding dislocation test demonstrated the better durability and glidability of the system. An in vivo animal experiment should be performed to further verify the system.

The survival benefit of metastasectomy for metastatic non-clear cell renal cell carcinoma: a retrospective cohort study.

PURPOSE: The aim of this study was to explore the benefit the metastasectomy for patients with metastatic non-clear cell carcinoma (non-ccRCC). METHODS: This study enrolled 120 patients with confirmed metastatic non-ccRCC from the RCC database of our center from 2008 to 2021. Patients without metastasectomy were grouped as radical nephrectomy without metastasectomy patients. The clinical outcomes included overall survival (OS) and progression-free survival (PFS). Cox regression and Kaplan-Meier analyses were used to assess potential factors that predict clinical benefits from metastasectomy. RESULTS: A total of 100 patients received radical nephrectomy alone, while the remaining 20 patients underwent both radical nephrectomy and metastasectomy. There was no significant difference in age between the two groups. Out of 100 patients who underwent radical nephrectomy, 60 were male, and out of 20 patients who had both radical nephrectomy and metastasectomy, 12 were male. Patients who underwent systemic therapy plus radical nephrectomy and metastasectomy had significantly better PFS (27.1 vs. 14.0, p = 0.032) and OS (67.3 vs. 24.0, p = 0.043) than those who underwent systemic therapy plus radical nephrectomy alone. Furthermore, for patients without liver metastasis (n = 54), systemic therapy plus radical nephrectomy and metastasectomy improved both PFS (p = 0.028) and OS (p = 0.043). Similarly, for patients with metachronous metastasis, systemic therapy plus radical nephrectomy and metastasectomy improved both PFS (p = 0.043) and OS (p = 0.032). None of the patients experienced serious perioperative complications (Clavien-Dindo Classification ≥ III grade). CONCLUSION: Metastasectomy in patients with metastatic non-ccRCC may provide clinical benefits in terms of improved PFS and OS, especially in patients without liver metastasis and those with metachronous metastasis.

HRU-Net: A high-resolution convolutional neural network for esophageal cancer radiotherapy target segmentation.

BACKGROUND AND OBJECTIVE: The effective segmentation of esophageal squamous carcinoma lesions in CT scans is significant for auxiliary diagnosis and treatment. However, accurate lesion segmentation is still a challenging task due to the irregular form of the esophagus and small size, the inconsistency of spatio-temporal structure, and low contrast of esophagus and its peripheral tissues in medical images. The objective of this study is to improve the segmentation effect of esophageal squamous cell carcinoma lesions. METHODS: It is critical for a segmentation network to effectively extract 3D discriminative features to distinguish esophageal cancers from some visually closed adjacent esophageal tissues and organs. In this work, an efficient HRU-Net architecture (High-Resolution U-Net) was exploited for esophageal cancer and esophageal carcinoma segmentation in CT slices. Based on the idea of localization first and segmentation later, the HRU-Net locates the esophageal region before segmentation. In addition, an Resolution Fusion Module (RFM) was designed to integrate the information of adjacent resolution feature maps to obtain strong semantic information, as well as preserve the high-resolution features. RESULTS: Compared with the other five typical methods, the devised HRU-Net is capable of generating superior segmentation results. CONCLUSIONS: Our proposed HRU-NET improves the accuracy of segmentation for squamous esophageal cancer. Compared to other models, our model performs the best. The designed method may improve the efficiency of clinical diagnosis of esophageal squamous cell carcinoma lesions.

Benzothiazole derivatives as histone deacetylase inhibitors for the treatment of autosomal dominant polycystic kidney disease.

Recent evidence suggests that histone deacetylases (HDACs) are important regulators of autosomal dominant polycystic kidney disease (ADPKD). In the present study, a series of benzothiazole-bearing compounds were designed and synthesized as potential HDAC inhibitors. Given the multiple participation of HDACs in ADPKD cyst progression, we embarked on a targeted screen using HeLa nuclear extracts to identify potent pan-HDAC inhibitors. Compound 26 emerged as the most efficacious candidate. Subsequent pharmacological characterization showed that compound 26 effectively inhibits several HDACs, notably HDAC1, HDAC2, and HDAC6 (IC50 < 150 nM), displaying a particularly high sensitivity towards HDAC6 (IC50 = 11 nM). The selected compound significantly prevented cyst formation and expansion in an in vitro cyst model and was efficacious in reducing cyst growth in both an embryonic kidney cyst model and an in vivo ADPKD mouse model. Our results provided compelling evidence that compound 26 represents a new HDAC inhibitor for the treatment of ADPKD.

Symmetry Evolution Induced Two-Dimensional Pt Single Atom Catalyst with High Density for Alkaline Hydrogen Oxidation.

The performance of single-atom catalysts is greatly influenced by the chemical environment surrounding the central atom. In this study, a salt-assisted method was employed to transform the tetrahedral coordination structure of ZIF-8 into a planar square coordination structure without altering the ligands. During the subsequent carbonization process, concurrent with the evaporation of zinc atoms, the structure of the nitrogen and carbon carriers (NC carriers) undergo a transition from five-membered rings to six-membered rings to preserve the 2D structure. Following carbonization, the 2d-NC carrier predominantly comprises pyridine N within six-membered rings, whereas the 3d-NC carrier contains a higher proportion of pyrrole N within five-membered rings, along with graphite N that unavailable for coordination sites. This transition result in the generation of additional defect sites on the 2d-NC substrates. Hence, the Pt single-atom catalysts with planar square coordination symmetries can be precisely prepared via electrodeposition (denoted as 2d-Pt SAC). By utilizing the structural characteristics of the 2d-NC carrier, it is beneficial to construct Pt SAs with higher density than that on 3d-NC. The Pt loading of 2d-Pt SAC is 0.49 ± 0.03 µg cm-2, higher than that of 3d-Pt SAC (0.37 ± 0.04 µg cm-2). In the context of the hydrogen oxidation reaction (HOR) electrocatalysis, these single atom catalysts with 2d coordination exhibited exchange current densities of 1.47 mA cm-2. Moreover, under an overpotential of 50 mV, it achieved mass activities of 2396 A gPt -1 (32 times higher than commercial Pt/C catalyst, 2 times higher than 3d-PtNC). Our findings elucidate the influence of coordination symmetry on the performance of single-atom catalysts, offering a novel synthetic approach that may have implications for future industrial synthesis endeavors. This article is protected by copyright. All rights reserved.

Hemostatic and Ultrasound-Controlled Bactericidal Silk Fibroin Hydrogel via Integrating a Perfluorocarbon Nanoemulsion.

Excessive blood loss and infections are the prominent risks accounting for mortality and disability associated with acute wounds. Consequently, wound dressings should encompass adequate adhesive, hemostatic, and bactericidal attributes, yet their development remains challenging. This investigation presented the benefits of incorporating a perfluorocarbon nanoemulsion (PPP NE) into a silk-fibroin (SF)-based hydrogel. By stimulating the ß-sheet conformation of the SF chains, PPP NEs drastically shortened the gelation time while augmenting the elasticity, mechanical stability, and viscosity of the hydrogel. Furthermore, the integration of PPP NEs improved hemostatic competence by boosting the affinity between cells and biomacromolecules. It also endowed the hydrogel with ultrasound-controlled bactericidal ability through the inducement of inner cavitation by perfluorocarbon and reactive oxygen species (ROS) generated by the sonosensitizer protoporphyrin. Ultimately, we employed a laparotomy bleeding model and a Staphylococcus aureus-infected trauma wound to demonstrate the first-aid efficacy. Thus, our research suggested an emulsion-incorporating strategy for managing emergency wounds.

Long-term variations of air pollutants and public exposure in China during 2000-2020.

Since 2000, China has faced severe air pollution challenges，prompting the initiation of comprehensive emission control measures post-2013. The subsequent implementation of these measures has led to remarkable enhancements in air quality. This study aims to enhance our understanding of the long-term trends in fine particulate matter (PM2.5) and gaseous pollutants of ozone (O3) and nitrogen dioxide (NO2) across China from 2000 to 2020. Utilizing the Community Multiscale Air Quality (CMAQ) model, we conducted a nationwide analysis of air quality, systematically quantifying model predictions against observations for pollutants. The CMAQ model effectively captured the trends of air pollutants, meeting recommended performance benchmarks. The findings reveal variations in pollutant concentrations, with initial increases in PM2.5 followed by a decline after 2013. The proportion of the population living in high PM2.5 concentrations (>75 µg/m3) decreased to <5 % after 2015. However, during the period from 2017 to 2020, around 40 % of the population continued to live in regions that did not meet the criteria for Chinese air quality standards (35 µg/m3). From 2000 to 2019, fewer than 20 % of the population met the WHO standard (100 µg/m3) for MDA8 O3. In 2000, 77 % of the population met the NO2 standard (<20 µg/m3), a figure that declined to 60 % between 2005 and 2014, nearly reaching 70 % in 2020. This study offers a comprehensive analysis of the changes in pollutants and public exposure in 2000-2020. It serves as a foundational resource for future efforts in air pollution control and health research.

Can the Sterilization Protocol Be Improved to Enhance the Healing of Allograft Tendons? An In Vivo Study in Rabbit Tendons.

BACKGROUND: Peracetic acid and irradiation are common sterilization methods for allograft tendons; however, under some conditions, both methods adversely affect the fiber arrangement and ultimate load of the tendon. An in vitro study showed that low-dose peracetic acid combined with irradiation may be less detrimental to allograft tendon structure and properties, possibly because the breakdown of peracetic acid can lead to an enlargement of the interstitial spaces and an increase in porosity. QUESTIONS/PURPOSES: Using a rabbit Achilles tendon model, we asked: What is the effect of peracetic acid-ethanol combined irradiation on (1) the histopathology and fiber diameter of the allograft tendon, (2) tensile creep and load-to-failure biomechanical properties of allograft tendons, and (3) healing of the treated tendon in vivo compared with fresh-frozen allograft and peracetic acid-ethanol sterilization at 4 and 8 weeks? METHODS: The Achilles tendons used in this study were sourced from euthanized 10-week-old male New Zealand White rabbits previously used for ophthalmic experiments. All allografts were divided into three groups: fresh-frozen group (control group, n = 20), peracetic acid-ethanol sterilization group (n =20), and peracetic acid-ethanol combined irradiation group (n = 20). The sterilization protocols were performed per a predetermined plan. In the peracetic acid-ethanol sterilization group, the tendon tissues were covered with the peracetic acid-ethanol sterilization solution (1% peracetic acid for 30 minutes). In the peracetic acid-ethanol combined irradiation group, the tendon tissues were covered with the peracetic acid-ethanol sterilization solution (0.2% peracetic acid for 30 minutes) and were subjected to 15 kGy gamma irradiation. Thirty 10-week-old male New Zealand White rabbits received bilateral Achilles tendon allografts surgically. Tendon samples from each group were harvested at 4 weeks (n = 30) and 8 weeks (n = 30) postoperatively. For each timepoint, eight tissues were used for histologic staining and electron microscopy, 15 tissues were used for biomechanical testing, and seven tissues were used for hydroxyproline assay and quantitative polymerase chain reaction. Histopathology was determined qualitatively by hematoxylin and eosin and Masson staining, while fiber diameter was measured quantitatively by transmission electron microscopy. Biomechanical properties were measured using cyclic loading tests and load-to-failure tests. The healing outcome was quantitatively judged through healing-related genes and proteins. RESULTS: At 4 weeks and 8 weeks postoperatively, the peracetic acid-ethanol combined irradiation group visually demonstrated the best continuity and minimal peripheral adhesions. Histologic staining showed that tendon fibers in the peracetic acid-ethanol combined irradiation group maintained consistent alignment without notable disruptions or discontinuities, and there was a qualitatively observed increase in the number of infiltrating cells compared with the control group at the 4-week timepoint (444 ± 49 /mm2 versus 256 ± 43 /mm2, mean difference 188 /mm2 [95% confidence interval 96 to 281]; p < 0.001). At 8 weeks postoperatively, the tendon fiber diameter in the peracetic acid-ethanol combined irradiation groups was similar to that of the control group (0.23 ± 0.04 µm versus 0.21 ± 0.03 µm, mean difference 0.02 µm [95% CI -0.04 to 0.08]; p = 0.56). At 8 weeks postoperatively, the peracetic acid-ethanol combined irradiation group exhibited better properties in terms of both ultimate load (129 ± 15 N versus 89 ± 20 N, mean difference 40 N [95% CI 7 to 73]; p = 0.02) and energy absorption density (17 ± 6 kJ/m2 versus 8 ± 4 kJ/m2, mean difference 8 kJ/m2 [95% CI 0.7 to 16]; p = 0.004) compared with the control group. Gene expression analysis revealed higher expression levels of COL1A1 (2.1 ± 0.8 versus 1.0 ± 0, mean difference 1.1 [95% CI 0.1 to 2.1]; p = 0.003) and MMP13 (2.0 ± 0.8 versus 1.0 ± 0, mean difference 1.0 [95% CI 0.4 to 1.6]; p = 0.03) in the peracetic acid-ethanol combined irradiation group than in the control group. There was a higher amount of collagen Type I in tendons treated with peracetic acid-ethanol combined irradiation than in the control group (0.36 ± 0.03 versus 0.31 ± 0.04, mean difference 0.05 [95% CI 0.01 to 0.09]; p = 0.02). CONCLUSION: Treatment with peracetic acid-ethanol combined irradiation did not have any discernible adverse effect on the histology, fiber diameter, enzymatic resistance, collagen content, or biomechanical strength of the allograft tendons compared with the control group. Peracetic acid-ethanol combined irradiation treatment had a positive impact on remodeling of the extracellular matrix and realignment of collagen fibers. CLINICAL RELEVANCE: This sterilization method could be helpful to expand the scope and frequency with which allogeneic materials are applied. The long-term healing effect and strength of allograft tendons must be tested before clinical use, and it is necessary to conduct comparative studies on autografts and synthetic materials that are currently widely used clinically.

High resolution spatiotemporal modeling of long term anthropogenic nutrient discharge in China.

High-resolution integration of large-scale and long-term anthropogenic nutrient discharge data is crucial for understanding the spatiotemporal evolution of pollution and identifying intervention points for pollution mitigation. Here, we establish the MEANS-ST1.0 dataset, which has a high spatiotemporal resolution and encompasses anthropogenic nutrient discharge data collected in China from 1980 to 2020. The dataset includes five components, namely, urban residential, rural residential, industrial, crop farming, and livestock farming, with a spatial resolution of 1 km and a temporal resolution of monthly. The data are available in three formats, namely, GeoTIFF, NetCDF and Excel, catering to GIS users, researchers and policymakers in various application scenarios, such as visualization and modelling. Additionally, rigorous quality control was performed on the dataset, and its reliability was confirmed through cross-scale validation and literature comparisons at the national and regional levels. These data offer valuable insights for further modelling the interactions between humans and the environment and the construction of a digital Earth.

Dual-energy computed tomography and micro-computed tomography for assessing bone regeneration in a rabbit tibia model.

To gain a more meaningful understanding of bone regeneration, it is essential to select an appropriate assessment method. Micro-computed tomography (Micro-CT) is widely used for bone regeneration because it provides a substantially higher spatial resolution. Dual-energy computed tomography (DECT) ensure shorter scan time and lower radiation doses during quantitative evaluation. Therefore, in this study, DECT and Micro-CT were used to evaluate bone regeneration. We created 18 defects in the tibial plateau of the rabbits and filled them with porous polyetheretherketone implants to promote bone regeneration. At 4, 8, and 12 weeks, Micro-CT and DECT were used to assess the bone repair in the defect region. In comparison to Micro-CT (152 ± 54 mg/cm3), the calcium density values and hydroxyapatite density values obtained by DECT [DECT(Ca) and DECT(HAP)] consistently achieved lower values (59 ± 25 mg/cm3, 126 ± 53 mg/cm3). In addition, there was a good association between DECT and Micro-CT (R = 0.98; R2 = 0.96; DECT(Ca): y = 0.45x-8.31; DECT(HAP): y = 0.95x-17.60). This study highlights the need to use two different imaging methods, each with its advantages and disadvantages, to better understand the bone regeneration process.

Enhancing Robot Task Planning and Execution through Multi-Layer Large Language Models.

Large language models have found utility in the domain of robot task planning and task decomposition. Nevertheless, the direct application of these models for instructing robots in task execution is not without its challenges. Limitations arise in handling more intricate tasks, encountering difficulties in effective interaction with the environment, and facing constraints in the practical executability of machine control instructions directly generated by such models. In response to these challenges, this research advocates for the implementation of a multi-layer large language model to augment a robot's proficiency in handling complex tasks. The proposed model facilitates a meticulous layer-by-layer decomposition of tasks through the integration of multiple large language models, with the overarching goal of enhancing the accuracy of task planning. Within the task decomposition process, a visual language model is introduced as a sensor for environment perception. The outcomes of this perception process are subsequently assimilated into the large language model, thereby amalgamating the task objectives with environmental information. This integration, in turn, results in the generation of robot motion planning tailored to the specific characteristics of the current environment. Furthermore, to enhance the executability of task planning outputs from the large language model, a semantic alignment method is introduced. This method aligns task planning descriptions with the functional requirements of robot motion, thereby refining the overall compatibility and coherence of the generated instructions. To validate the efficacy of the proposed approach, an experimental platform is established utilizing an intelligent unmanned vehicle. This platform serves as a means to empirically verify the proficiency of the multi-layer large language model in addressing the intricate challenges associated with both robot task planning and execution.

Elevated level of circulating calprotectin correlates with severity and high mortality in patients with COVID-19.

BACKGROUND: Patients with coronavirus disease-2019 (COVID-19) are characterized by hyperinflammation. Calprotectin (S100A8/S100A9) is a calcium- and zinc-binding protein mainly secreted by neutrophilic granulocytes or macrophages and has been suggested to be correlated with the severity and prognosis of COVID-19. AIM: To thoroughly evaluate the diagnostic and prognostic utility of calprotectin in patients with COVID-19 by analyzing relevant studies. METHODS: PubMed, Web of Science, and Cochrane Library were comprehensively searched from inception to August 1, 2023 to retrieve studies about the application of calprotectin in COVID-19. Useful data such as the level of calprotectin in different groups and the diagnostic efficacy of this biomarker for severe COVID-19 were extracted and aggregated by using Stata 16.0 software. RESULTS: Fifteen studies were brought into this meta-analysis. First, the pooled standardized mean differences (SMDs) were used to estimate the differences in the levels of circulating calprotectin between patients with severe and non-severe COVID-19. The results showed an overall estimate of 1.84 (95% confidence interval [CI]: 1.09-2.60). Diagnostic information was extracted from 11 studies, and the pooled sensitivity and specificity of calprotectin for diagnosing severe COVID-19 were 0.75 (95% CI: 0.64-0.84) and 0.88 (95% CI: 0.79-0.94), respectively. The AUC was 0.89 and the pooled DOR was 18.44 (95% CI: 9.07-37.51). Furthermore, there was a strong correlation between elevated levels of circulating calprotectin and a higher risk of mortality outcomes in COVID-19 patients (odds ratio: 8.60, 95% CI: 2.17-34.12; p < 0.1). CONCLUSION: This meta-analysis showed that calprotectin was elevated in patients with severe COVID-19, and this atypical inflammatory cytokine might serve as a useful biomarker to distinguish the severity of COVID-19 and predict the prognosis.

Chlorocholine chloride exposure induced spermatogenic dysfunction via iron overload caused by AhR/PERK axis-dependent ferritinophagy activation.

Chlorocholine chloride (CCC) is a plant growth regulator used worldwide that is detectable in cereals, fruits and animal products. The health effects of CCC exposure have raised public concern. Our previous research showed that CCC exposure decreased testosterone synthesis in pubertal rats. However, little is known about whether and how pubertal CCC exposure impacts spermatogenesis. In this study, we used BALB/c mice and spermatogonia-derived GC-1 cells to examine CCC-induced spermatogenic dysfunction. In vivo, pubertal CCC exposure led to decreased testicular weight, decreased testicular germ cells and poor sperm quality. This effect worsened after cessation of CCC exposure for the next 30 days. RNA-seq and western blot analysis revealed that CCC induced aryl hydrocarbon receptor (AhR) signaling, endoplasmic reticulum stress (ERS) and ferritinophagy. Increased iron content and lipid peroxidation levels were also observed in CCC-treated testes. In vitro, it was identified that iron overload mediated by enhanced ferritinophagy occurred in CCC-treated GC-1 cells, which might be attributed to the PERK pathway in ERS. Further, for the first time, our study elucidated the involvement of AhR in CCC-induced iron overload, which aggravated testicular oxidative damage via lipid peroxidation. Considering the adverse impact of CCC exposure on rodents, supportive evidence from GC-1 cells, and the critical importance of spermatogenesis on male development, the effects of CCC on the male reproduction warrant increased attention.

The extrachromosomal circular DNA atlas of aged and young mouse brains.

Extrachromosomal circular DNA (eccDNA) refers to a distinct class of circular DNA molecules that exist independently from linear chromosomal DNA. Extensive evidence has firmly established the significant involvement of eccDNA in cancer initiation, progression, and evolutionary processes. However, the relationship between eccDNA and brain aging remains elusive. Here, we employed extrachromosomal circular DNA sequencing (Circle-seq) to generate a comprehensive dataset of eccDNA from six brain structures of both young and naturally-aged mice, including the olfactory bulb, medial prefrontal cortex, nucleus accumbens, caudate putamen, hippocampus, and cerebellum. Furthermore, through database annotation, we characterized the properties of mouse brain eccDNA, thereby gaining insights into the potential functions of eccDNA in the mouse brain. In conclusion, our study addresses a previously unexplored area by providing a comprehensive molecular characterization of eccDNA in brain tissues. The data presented in the study can be used as a fundamental resource to associate the molecular phenotypes of eccDNA with brain aging and gain deep insights into the biological role of eccDNA in mammalian brain aging.

Sex and age disparities in multi-metal mixture exposure and cognitive impairment in urban elderly individuals: The mediation effect and biological function of metabolites.

Studies on the relationships between metal mixtures exposure and cognitive impairment in elderly individuals are limited, particularly the mechanism with metabolite. Few studies are available on the potential sex and age specific associations between metal exposure, metabolites and cognitive impairment. We examined plasma metal and blood metabolite concentrations among 1068 urban elderly participants. Statistical analysis included a battery of variable selection approaches, logistic regression for metal/metabolite associations, and Bayesian kernel machine regression (BKMR) to identify mixed effects of metals/metabolites on cognitive impairment risk. Our results showed that As was positively associated with cognitive impairment in the female (OR 95 % CI = 2.21 (1.36, 3.57)) and 60- to 70-year-old (OR 95 % CI = 2.60 (1.54, 4.41)) groups, Cr was positively associated with cognitive impairment in the male (OR 95 % CI = 2.15 (1.27, 3.63)) and 60- to 70-year-old (OR 95 % CI = 2.10 (1.24, 3.57)) groups, and Zn was negatively associated with cognitive impairment, especially in the female (OR 95 % CI = 0.46 (0.25, 0.84)), 60- to 70-year-old (OR 95 % CI =0.24 (0.12, 0.45)) and ≥ 80-year-old (OR 95 % CI = 0.19 (0.04, 0.86)) groups. Positive associations were observed between combined metals (Cr, Cu and As) and cognitive impairment, but Zn alleviated this tendency, especially in elderly individuals aged ≥80 years. Negative associations were observed between metabolites and cognitive impairment, especially in male, female and 60-70 years old groups. The mediation effects of metabolites on the association between metal exposure and cognitive impairment were observed, and the percentages of these effects were 15.60 % (Glu-Cr), 23.00 % (C5:1-Cu) and 16.36 % (Glu-Zn). Cr, Cu, and Zn could increase cognitive impairment risk through the "Malate-Aspartate Shuttle", "Glucose-Alanine Cycle", etc., pathways. Overall, we hypothesize that metabolites have mediation effects on the relationship between multi-metal exposure and cognitive impairment and that there are sex and age differences.

KSHV vIL-6 promotes SIRT3-induced deacetylation of SERBP1 to inhibit ferroptosis and enhance cellular transformation by inducing lipoyltransferase 2 mRNA degradation.

Ferroptosis, a defensive strategy commonly employed by the host cells to restrict pathogenic infections, has been implicated in the development and therapeutic responses of various types of cancer. However, the role of ferroptosis in oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV)-induced cancers remains elusive. While a growing number of non-histone proteins have been identified as acetylation targets, the functions of these modifications have yet to be revealed. Here, we show KSHV reprogramming of host acetylation proteomics following cellular transformation of rat primary mesenchymal precursor. Among them, SERPINE1 mRNA binding protein 1 (SERBP1) deacetylation is increased and required for KSHV-induced cellular transformation. Mechanistically, KSHV-encoded viral interleukin-6 (vIL-6) promotes SIRT3 deacetylation of SERBP1, preventing its binding to and protection of lipoyltransferase 2 (Lipt2) mRNA from mRNA degradation resulting in ferroptosis. Consequently, a SIRT3-specific inhibitor, 3-TYP, suppresses KSHV-induced cellular transformation by inducing ferroptosis. Our findings unveil novel roles of vIL-6 and SERBP1 deacetylation in regulating ferroptosis and KSHV-induced cellular transformation, and establish the vIL-6-SIRT3-SERBP1-ferroptosis pathways as a potential new therapeutic target for KSHV-associated cancers.

Asymmetric synthesis of P-stereogenic phosphindane oxides via kinetic resolution and their biological activity.

The importance of P-stereogenic heterocycles has been widely recognized with their extensive use as privileged chiral ligands and bioactive compounds. The catalytic asymmetric synthesis of P-stereogenic phosphindane derivatives, however, remains a challenging task. Herein, we report a catalytic kinetic resolution of phosphindole oxides via rhodium-catalyzed diastereo- and enantioselective conjugate addition to access enantiopure P-stereogenic phosphindane and phosphindole derivatives. This kinetic resolution method features high efficiency (s factor up to >1057), excellent stereoselectivities (all >20:1 dr, up to >99% ee), and a broad substrate scope. The obtained chiral phosphindane oxides exhibit promising therapeutic efficacy in autosomal dominant polycystic kidney disease (ADPKD), and compound 3az is found to significantly inhibit renal cyst growth both in vitro and in vivo, thus ushering in a promising scaffold for ADPKD drug discovery. This study will not only advance efforts towards the asymmetric synthesis of challenging P-stereogenic heterocycles, but also surely inspire further development of P-stereogenic entities for bioactive small-molecule discovery.

Next-generation endoscopic probe for detection of esophageal dysplasia using combined OCT and angle-resolved low-coherence interferometry.

Angle-resolved low-coherence interferometry (a/LCI) is an optical technique that enables depth-specific measurements of nuclear morphology, with applications to detecting epithelial cancers in various organs. Previous a/LCI setups have been limited by costly fiber-optic components and large footprints. Here, we present a novel a/LCI instrument incorporating a channel for optical coherence tomography (OCT) to provide real-time image guidance. We showcase the system's capabilities by acquiring imaging data from in vivo Barrett's esophagus patients. The main innovation in this geometry lies in implementing a pathlength-matched single-mode fiber array, offering substantial cost savings while preserving signal fidelity. A further innovation is the introduction of a specialized side-viewing probe tailored for esophageal imaging, featuring miniature optics housed in a custom 3D-printed enclosure attached to the tip of the endoscope. The integration of OCT guidance enhances the precision of tissue targeting by providing real-time morphology imaging. This novel device represents a significant advancement in clinical translation of an enhanced screening approach for esophageal precancer, paving the way for more effective early-stage detection and intervention strategies.