Yishen Huazhuo decoction regulates microglial polarization to reduce Alzheimer's disease-related neuroinflammation through TREM2.

Background: Aging is the primary risk factor for the onset of Alzheimer's disease (AD). Inflamma-aging is a major feature in the process of aging, and the chronic neuroinflammation caused by inflamma-aging is closely related to AD. As the main participant of neuroinflammation, the polarization of microglia (MG) could influence the development of neuroinflammation. Objective: This study aims to observe the impact of YHD on microglia (MG) polarization and neuroinflammation to delay the onset and progression of AD. Methods: In vivo experiment, four-month senescence accelerated mouse prone 8 (SAMP8) were used as the model group, the SAMR1 mice of the same age were used as the control group. In YHD group, 6.24 g/kg YHD was intragastrically administrated continuously for 12 weeks, and Ibuprofen 0.026 g/kg in positive control group. Morris Water Maze test was used to evaluate the learning and memory ability, Nissl's staining and immunofluorescence double staining for neuron damage and MG M1/M2 polarization, Enzyme-Linked Immunosorbent Assay (ELISA) for neuroinflammation biomarkers in hippocampus, Western blot for key protein expression of TREM2/NF-κB signaling pathway. In vitro experiments, 10 µM/l Aß1-42 induced BV-2 cell model was used to re-verify the effect of YHD regulating MG polarization to reduce neuroinflammation. Also, TREM2 small interfering RNA (siRNA) was used to clarify the key target of YHD. Results: YHD could improve the learning and memory ability of SAMP8 mice evaluated by the Morris Water Maze test. Like Ibuprofen, YHD could regulate the M1/M2 polarization of MG and the levels of neuroinflammatory markers TNF-α and IL-10 in hippocampus, and relieve neuroinflammation and neuron loss. In addition, YHD could also regulate the expression of PU.1, TREM2, p-NF-κB P65 in the TREM2/NF-κB signaling pathway. Further in vitro experiments, we found that YHD had a significant regulatory effect on Aß1-42-induced BV-2 cell polarization, and it could significantly increase PU.1, TREM2, decrease p-NF-κB P65, p-IKKß, TNF-α, IL-6, IL-1ß. At the same time, using siRNA to inhibit TREM2, it proved that TREM2 was a key target for YHD to promote Aß1-42-induced BV-2 cell M2 polarization to reduce neuroinflammation. Conclusions: YHD could regulate the TREM2/NF-κB signaling pathway through TREM2, thereby to adjust MG polarization and reduce AD-related neuroinflammation.

Nucleic acid-functionalized upconversion luminescence biosensor based on strand displacement-mediated signal amplification for the detection of trivalent chromium ions.

BACKGROUND: Rapid industrial development has generated serious pollution, including the presence of toxic and harmful heavy metal ions. Among them, trivalent chromium ion (Cr3+) is a very important element that poses a threat to life and health in our industrial wastewater pollution. Thus, it is important to develop efficient fluorescence methods for Cr3+ detection. In this study, an upconversion luminescence biosensor for detecting Cr3+ was constructed based on a DNAzyme, strand displacement reaction (SDR), and DNA-functionalized upconversion nanoparticles (UCNPs). RESULTS: The sulfonate-rich poly (sodium 4-styrene sulfonate) (PSS) was modified onto the surface of UCNPs, forming UCNPs@PSS. Then, NH2-Capture probe DNA (NH2-Cp) was further modified onto the UCNPs@PSS surface through sulfonylation, resulting in UCNPs@PSS@NH2-Cp. The DNAzyme activated by Cr3+ triggered the release of the primer probe (Pp), which initiated the SDR system cycle, thereby releasing a tetramethylrhodamine (TAMRA)-modified signal probe (TAMRA-Sp). Finally, UCNPs@PSS@NH2-Cp bound to TAMRA-Sp through complementary base pairing, causing UCNPs and TAMRA to approach each other. Because of the luminescence resonance energy transfer (LRET) mechanism, the upconversion luminescence (UCL) signal of the UCNPs was quenched by TAMRA, enabling the detection of Cr3+ by the change of I585/I545 ratio. This biosensor has good stability, selectivity, and sensitivity, with a linear range of 0.5-75 nM and a detection limit of 0.135 nM for Cr3+. SIGNIFICANCE AND NOVELTY: Firstly, based on LRET between UCNPs and TAMRA, the quantitative analysis of Cr3+ is achieved through the changes of ratio fluorescence. Secondly, the specificity of the biosensor is improved by utilizing the specific recognition of DNA enzymes. Thirdly, the signal amplification technology of the SDR cycle greatly improves the sensitivity of biosensor. This biosensor will be useful for future environmental safety monitoring and biopsy of biological fluids.

Preconcentration and detection of SARS-CoV-2 in wastewater: A comprehensive review.

Severe acute respiratory syndrome coronaviruses 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) affected the health of human beings and the global economy. The patients with SARS-CoV-2 infection had viral RNA or live infectious viruses in feces. Thus, the possible transmission of SARS-CoV-2 through wastewater received great attentions. Moreover, SARS-CoV-2 in wastewater can serve as an early indicator of the infection within communities. We summarized the preconcentration and detection technology of SARS-CoV-2 in wastewater aiming at the complex matrices of wastewater and low virus concentration and compared their performance characteristics. We described the emerging tests that would be possible to realize the rapid detection of SARS-CoV-2 in fields and encourage academics to advance their technologies beyond conception. We concluded with a brief discussion on the outlook for integrating preconcentration and the detection of SARS-CoV-2 with emerging technologies.

The evolution of simulation-based medical education research: From traditional to virtual simulations.

Background: Simulation-based medical education (SBME) is a widely used method in medical education. This study aims to analyze publications on SBME in terms of countries, institutions, journals, authors, and keyword co-occurrence, as well as to identify trends in SBME research. Methods: We retrieved the Publications on SBME from the Web of Science Core Collection (WoSCC) database from its inception to January 27, 2024. Microsoft Excel 2019, CiteSpace, and VOSviewer were used to identify the distribution of countries, journals, and authors, as well as to determine the research hotspots. Results: We retrieved a total of 11272 publications from WoSCC. The number of documents published in 2022 was the highest in the last few decades. The USA, the UK, and Canada were three key contributors to this field. The University of Toronto, Stanford University, and Harvard Medical School were the top major institutions with a larger number of publications. Konge, Lars was the most productive author, while McGaghie, William C was the highest cited author. BMC Medical Education has the highest number of publications among journals. The foundational themes of SBME are "Patient simulation," "extending reality," and "surgical skills." Conclusions: SBME has attracted considerable attention in medical education. The research hotspot is gradually shifting from traditional simulations with real people or mannequins to virtual, digitally-based simulations and online education. Further studies will be conducted to elucidate the mechanisms of SBME. The utilization of SBME will be more rationalized.

Chiglitazar attenuates high-fat diet-induced nonalcoholic fatty liver disease by modulating multiple pathways in mice.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide; however, effective intervention strategies for NAFLD are still unavailable. The present study sought to investigate the efficacy of chiglitazar, a pan-PPAR agonist, in protecting against NAFLD in mice and its underlying molecular mechanism. Male C57BL/6 J mice were fed a high-fat diet (HFD) for 8 weeks to generate NAFLD and the HFD was continued for an additional 10 weeks in the absence or presence of 5 mg/kg/d or 10 mg/kg/d chiglitazar by gavage. Chiglitazar significantly improved dyslipidemia and insulin resistance, ameliorated hepatic steatosis and reduced liver inflammation and oxidative stress in NAFLD mice. RNA-seq revealed that chiglitazar alleviated HFD-induced NAFLD in mice through multiple pathways, including fatty acid metabolism regulation, insulin signaling pathway, and AMPK signaling pathway. This study demonstrated the potential therapeutic effect of chiglitazar on NAFLD. Chiglitazar ameliorated NAFLD by modulating multiple pathways.

KPNA2 promotes the progression of gastric cancer by regulating the alternative splicing of related genes.

RNA-binding proteins (RBPs) play critical roles in genome regulation. In this study, we explored the latent function of KPNA2, which is an essential member of the RBP family, in the regulation of alternative splicing (AS) in gastric cancer (GC). We analyzed the role of KPNA2 in regulating differential expression and AS via RNA sequencing (RNA-seq) and improved RNA immunoprecipitation sequencing (iRIP-seq). Clinical specimens were used to analyze the associations between KPNA2 expression and clinicopathological characteristics. CCK8 assays, transwell assays and wound healing assays were performed to explore the effect of KPNA2/WDR62 on GC cell progression. KPNA2 was shown to be highly expressed in GC cells and tissues and associated with lymph node metastases. KPNA2 promoted the proliferation, migration and invasion of GC cells and primarily regulated exon skipping, alternative 3's splice sites (A3SSs), alternative 5' splice sites (A5SSs), and cassette exons. We further revealed that KPNA2 participated in biological processes related to cell proliferation, and the immune response in GC via the regulation of transcription. In addition, KPNA2 preferentially bound to intron regions. Notably, KPNA2 regulated the A3SS AS mode of WDR62, and upregulation of WDR62 reversed the KPNA2 downregulation-induced inhibition of GC cell proliferation, migration and invasion. Finally, we discovered that the AS of immune-related molecules could be regulated by KPNA2. Overall, our results demonstrated for the first time that KPNA2 functions as an oncogenic splicing factor in GC that regulated the AS and differential expression of GC-related genes, and KPNA2 may be a potential target for GC treatment.

Frontier and hot topics in the application of hydrogel in the biomedical field: a bibliometric analysis based on CiteSpace.

Hydrogels are formed of crosslinked polymer chains arranged in three-dimensional (3D) networks. These chains have good water-containing capacity and are soft and malleable. Hydrogels have good biocompatibility due to their significant water content, flexible structure, and numerous holes. These characteristics make them analogous to biological tissues. Despite the publication of 8700 literature related to hydrogel biomedical applications in the past 52 years (1973 ~ 2024), studies on the use of hydrogels in biomedicine are few. To gain a comprehensive understanding of their current development status, research trends, and prospects in the biomedical application field, it is imperative to conduct a thorough retrospective analysis. In this study, we employ bibliometric analysis and CiteSpace software to quantitatively and visually analyze articles published in this field. Firstly, we provide a quantitative analysis of authorship and institutional publications over the past 52 years to elucidate the fundamental development status regarding hydrogel biomedical applications. Secondly, we did visual studies on terms that are high-frequency, explosive, keyword clustering, and so on, to understand the directionality and evolution of the main research hotspots during each period. Notably, our findings emphasize that fabricating hydrogels into wound healing-promoting dressings emerges as a prominent hotspot within the application field. We anticipate that this paper will inspire researchers with novel ideas for advancing hydrogel applications in biomedicine.

Exosomal noncoding RNAs: decoding their role in thyroid cancer progression.

Exosomes, as pivotal entities within the tumor microenvironment, orchestrate intercellular communication through the transfer of diverse molecules, among which non-coding RNAs (ncRNAs) such as miRNAs, lncRNAs, and circRNAs play a crucial role. These ncRNAs, endowed with regulatory functions, are selectively incorporated into exosomes. Emerging evidence underscores the significance of exosomal ncRNAs in modulating key oncogenic processes in thyroid cancer (TC), including proliferation, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and immunoediting. The unique composition of exosomes shields their cargo from enzymatic and chemical degradation, ensuring their integrity and facilitating their specific expression in plasma. This positions exosomal ncRNAs as promising candidates for novel diagnostic and prognostic biomarkers in TC. Moreover, the potential of exosomes in the therapeutic landscape of TC is increasingly recognized. This review aims to elucidate the intricate relationship between exosomal ncRNAs and TC, fostering a deeper comprehension of their mechanistic involvement. By doing so, it endeavors to propel forward the exploration of exosomal ncRNAs in TC, ultimately paving the way for innovative diagnostic and therapeutic strategies predicated on exosomes and their ncRNA content.

Suzuki-Miyaura Cross-Coupling Reaction Catalyzed by Al12M (M = Be, Al, C, and P) Superatoms with Different Numbers of Valence Electrons.

The exploration of low-cost, efficient, environmentally safe, and selective catalysts for the activation of carbon-halogen bonds has become an important and challenging topic in modern chemistry. With the help of density functional theory (DFT), it is found that phenyl bromide (PhBr) can be efficiently chemisorbed by the Al12M (M = Be, Al, C, and P) superatoms via forming highly polarized Al-Br covalent bonds, where the C-Br bonds of PhBr can be effectively activated through the electron transfer from Al12M. The different electronic structures of these four Al12M superatoms pose a substantial effect on their performances on the activation of PhBr and the catalytic mechanisms of the Suzuki-Miyaura (SM) reaction. Among them, the alkali-metal-like superatom Al12P exhibits the best performance for the activation of PhBr. In particular, Al13 and Al12P with open-shell electronic structures exhibit catalytic performances comparable to those of previously reported catalysts for this coupling reaction. Hence, it is highly expected that Al13 and Al12P could be used as novel superatom catalysts for C-C coupling reactions and, therefore, open up new possibilities to use nonprecious superatoms in catalyzing the activation and transformation of carbon-halogen bonds.

Enzyme-activatable charge transfer in gold nanoclusters.

Surface-protecting ligands, as a major component of metal nanoclusters (MNCs), can dominate molecular characteristics, performance behaviors, and biological properties of MNCs, which brings diversity and flexibility to the nanoclusters and largely promotes their applications in optics, electricity, magnetism, catalysis, biology, and other fields. We report herein the design of a new kind of water-soluble luminescent gold nanoclusters (AuNCs) for enzyme-activatable charge transfer (CT) based on the ligand engineering of AuNCs with 6-mercaptopurine ribonucleoside (MPR). This elaborately designed cluster, Au5(MPR)2, can form a stable intramolecular CT state after light excitation, and exhibits long-lived color-tunable phosphorescence. After the cleavage by purine nucleoside phosphorylase (PNP), the CT triplet state can be easily directed to a low-lying energy level, leading to a bathochromic shift of the emission band accompanied by weaker and shorter-lived luminescence. Remarkably, these ligand-engineered AuNCs show high affinity towards PNP as well as decent performance for analyzing and visualizing enzyme activity and related drugs. The work of this paper provides a good example for diversifying physicochemical properties and application scenarios of MNCs by rational ligand engineering, which will facilitate future interest and new strategies to precisely engineer solution-based nanocluster materials.

Dysphagia in Parkinson's disease: A bibliometric and visualization analysis from 2002 to 2022.

Background: Dysphagia, or difficulty swallowing, is a prevalent complication of Parkinson's disease (PD), which can significantly impair quality of life. Despite the numerous studies on dysphagia in PD published in various journals, there remains a dearth of bibliometric analysis within this domain. This study thus aims to examine the global patterns of research on dysphagia after PD over the past 20 years, employing a visual analysis. Material and methods: This investigation aimed to gather pertinent publications concerning dysphagia in PD from the SCI-Expanded database of the Web of Science Core Collection (WoSCC), covering the period from 2002 to 2022. To dissect and visually represent the collated corpus, we harnessed the capacities of CiteSpace, VOSviewer and R software for meticulous bibliometric scrutiny. Results: The bibliometric study encompassed a total of 692 publications. Within the scope of autocratic nations, the USA emerged as the leading country in the quantity of research outputs. The University of Florida stood out as the most prolific academic entity, with Troche MS being the foremost author, contributing to 21 publications. The journal "Dysphagia" featured as the prime venue for publication. Key trending terms identified over the last 20 years include "Parkinson's disease," "dysphagia," "oropharyngeal dysphagia," and "prevalence." Conclusion: Bibliometric analysis on dysphagia in PD offers a detailed overview of the development of scholarly publications, enabling scholars to grasp the current state of research within their field. It also serves as a benchmark for shaping future research directions.

Visual trends and hot research on the relationship between intestinal microbiota and major lipids: a bibliometric analysis.

Objective: The association between intestinal microbiota and lipids has garnered significant scholarly interest. This study analyzes pertinent literature on intestinal microbiota and lipids to offer scientific guidance for future advancements and research directions. Methods: Articles focusing on intestinal microbiota and lipids were obtained from the Web of Science Core Collection (WoSCC). Following a rigorous screening process, 12,693 articles were included in the study. The collected data was processed comprehensively and visually analyzed using various academic tools such as CiteSpace, VOSviewer, R software, and Scimago Graphica. Results: The field of intestinal microbiota and its relationship with major lipids has witnessed a significant surge in scholarly attention, as indicated by the upward trend observed in related articles. Among countries, China had emerged as the leading contributor in publication output, with Chinese Acad Sci being the most prolific institution in this field. Notably, Nutrients and Nature were the prominent journals that published many articles and garnered the highest number of co-citations. Scholars have widely recognized Patrice D Cani's notable contributions in this field. Current research endeavors have focused on obesity, insulin resistance, metabolism, growth performance, the gut-brain axis, and others. Conclusions: Our analysis identified four primary research trends: "biochemical pathways," "exploration of diseases," "intervention and effect," and "health and diet." Future scholars must devote more attention to intestinal microbiota and major lipids to advance our understanding of human health.

Design and Experiment of an Unoccupied Control System for a Tracked Grain Vehicle.

In order to enhance crop harvesting efficiency, an automatic-driving tracked grain vehicle system was designed. Based on the harvester chassis, we designed the mechanical structure of a tracked grain vehicle with a loading capacity of 4.5 m3 and a grain unloading hydraulic system. Using the BODAS hydraulic controller, we implemented the design of an electronic control system that combines the manual and automatic operation of the chassis walking mechanism and grain unloading mechanism. We utilized a hybrid A* algorithm to plan the traveling path of the tracked grain vehicle, and the path-tracking controller of the tracked grain vehicle was designed by combining fuzzy control and pure pursuit algorithms. Leveraging binocular vision technology and semantic segmentation technology, we designed an automatic grain unloading control system with functions of grain tank recognition and grain unloading regulation control. Finally, we conducted experiments on automatic grain unloading control and automatic navigation control in the field. The results showed that both the precision of the path-tracking control and the automatic unloading system meet the requirements for practical unoccupied operations of the tracked grain vehicle.

Chemo-photodynamic antitumour therapy based on Er-doped upconversion nanoparticles coated with hypocrellin B and MnO2.

An antitumour chemo-photodynamic therapy nanoplatform was constructed based on phospholipid-coated NaYF4: Yb/Er upconversion nanoparticles (UCNPs). In this work, the amphiphilic block copolymer DSPE-PEG2000 was combined with the surface ligand oleic acid of the UCNPs through hydrophobic interaction to form liposomes with a dense hydrophobic layer in which the photosensitizer hypocrellin B (HB) was assembled. The coated HB formed J-aggregates, which caused a large redshift in the absorption spectrum and improved the quantum efficiency of energy transfer. Furthermore, MnO2 nanosheets grew in-situ on the liposomes through OMn coordination. Therefore, a multifunctional tumour microenvironment (TME)-responsive theranostic nanoplatform integrating photodynamic therapy (PDT) and chemodynamic therapy (CDT) was successfully developed. The results showed that this NIR-mediated chemo-photodynamic therapy nanoplatform was highly efficient for oncotherapy.

Full-Scale Model Tests of Two Box-Type Soil-Steel Structures with Different Crown and Haunch Radii.

Compared with circular, arched, and pipe-arched soil-steel structures, box-type soil-steel structures (BTSSSs) have the advantages of high cross-section utilization and low cover depth. However, the degree of influence of the crown and haunch radii on the mechanical performance of BTSSSs is still unclear. Therefore, two full-scale BTSSS models with a span of 6.6 m and a rise of 3.7 m but with different crown and haunch radii were established, and the mechanical properties during backfilling and under live load were tested. Afterward, 2D finite element models (FEMs) were established using the ABAQUS 2020 software and verified using the test data. The influence of cross-section geometric parameters on mechanical performance was analyzed by using the FEM, and a more accurate formula for calculating the bending moment during backfilling was proposed. The results show that the BTSSS with a smaller crown radius has a stronger soil-steel interaction, which promotes more uniform stress on the structure and makes the structure have smaller relative deformations, bending moments, and earth pressure. The span and arch height greatly influence the bending moment and deformation of the structure. Based on the CHBDC, the crown and haunch radii were included in the revised calculation formula.

Causal effects of immune cell surface antigens and functional outcome after ischemic stroke: a Mendelian randomization study.

Objective: While observational studies link immune cells with post-stroke functional outcome, the underlying immune mechanisms are not well understood. Immune cell surface antigens are actively involved in the biological behavior of immune cells, investigating immune cell surface antigens could deepen our comprehension of their role and biological processes in stroke recovery. Therefore, we aimed to investigate the immunological basis of stroke outcome by exploring the causal relationship between immune cell surface antigens and functional outcome after ischemic stroke in a Mendelian randomization study. Methods: Genetic variants related to immune cell surface antigens and post-stroke functional outcome were selected for two-sample Mendelian randomization (MR) analysis. 389 fluorescence intensities (MFIs) with surface antigens were included. Inverse variance weighted (IVW) modeling was used as the primary MR method to estimate the causal effect of exposure on the outcome, followed by several alternative methods and sensitivity analyses. Additional analysis of the association between immune cell surface antigens and risk of ischemic stroke for assessment of collider bias. Results: We found that suggestive associations between CD20 on switched memory B cell (OR = 1.16, 95% CI: 1.01-1.34, p = 0.036) and PDL-1 on monocyte (OR = 1.32, 95% CI: 1.04-1.66, p = 0.022) and poor post-stroke functional outcome, whereas CD25 on CD39+ resting Treg (OR = 0.77, 95% CI: 0.62-0.96, p = 0.017) was suggestively associated with good post-stroke functional outcome. Conclusion: The elevated CD20 on switched memory B cell, PDL-1 on monocyte, and CD25 on CD39+ resting Treg may be novel biomarkers and potential causal factors influencing post-stroke functional outcome.

Unraveling a Concerted Proton-Coupled Electron Transfer Pathway in Atomically Precise Gold Nanoclusters.

Metal nanoclusters (MNCs) represent a promising class of materials for catalytic carbon dioxide and proton reduction as well as dihydrogen oxidation. In such reactions, multiple proton-coupled electron transfer (PCET) processes are typically involved, and the current understanding of PCET mechanisms in MNCs has primarily focused on the sequential transfer mode. However, a concerted transfer pathway, i.e., concerted electron-proton transfer (CEPT), despite its potential for a higher catalytic rate and lower reaction barrier, still lacks comprehensive elucidation. Herein, we introduce an experimental paradigm to test the feasibility of the CEPT process in MNCs, by employing Au18(SR)14 (SR denotes thiolate ligand), Au22(SR)18, and Au25(SR)18- as model clusters. Detailed investigations indicate that the photoinduced PCET reactions in the designed system proceed via an CEPT pathway. Furthermore, the rate constants of gold nanoclusters (AuNCs) have been found to be correlated with both the size of the cluster and the flexibility of the Au-S framework. This newly identified PCET behavior in AuNCs is prominently different from that observed in semiconductor quantum dots and plasmonic metal nanoparticles. Our findings are of crucial importance for unveiling the catalytic mechanisms of quantum-confined metal nanomaterials and for the future rational design of more efficient catalysts.

Optimizing Salt Leakage Mitigation and Comparing Sorption-Desorption Characteristics of Polyacrylamide-Based Hydrogels.

Solid hygroscopic materials are extensively utilized in diverse fields, including adsorption heat transfer, adsorption heat storage, atmospheric water harvesting (AWH), and air conditioning dehumidification. The efficacy and energy efficiency of these materials in practical applications are significantly influenced by their adsorption and desorption properties. Yet, the introduction of inorganic salts to boost adsorption performance can result in issues like salt leakage. In this research, we prepared a polyacrylamide hydrogel through free radical polymerization, and its water-absorbing capabilities were improved by incorporating the hygroscopic salt lithium chloride. We compared it to a salt-based porous adsorbent, AlFum-LiCl, which also exhibited strong water adsorption properties and the potential for large-scale production. While AlFum-LiCl suffered from limited pores and salt leakage during high water uptake, the optimized PAM-LiCl displayed superior water sorption capabilities, showing no salt leakage even at water uptake of up to 3.5 g/g. At 25 °C, PAM-LiCl achieved equilibrium water uptake of 1.26 g/g at 30% RH and 3.15 g/g at 75% RH. In this context, utilizing 20 g of PAM-LiCl for the AWH experiment yielded daily water outputs of 8.34 L/kg at 30% RH and 16.86 L/kg at 75% RH. The salt-optimized PAM-LiCl hydrogel offers the benefit of application in higher relative humidity environments without the risk of deliquescence, underscoring its promise for atmospheric water harvesting.

Diabetes-induced male infertility: potential mechanisms and treatment options.

Male infertility is a physiological phenomenon in which a man is unable to impregnate a fertile woman during a 12-month period of continuous, unprotected sexual intercourse. A growing body of clinical and epidemiological evidence indicates that the increasing incidence of male reproductive problems, especially infertility, shows a very similar trend to the incidence of diabetes within the same age range. In addition, a large number of previous in vivo and in vitro experiments have also suggested that the complex pathophysiological changes caused by diabetes may induce male infertility in multiple aspects, including hypothalamic-pituitary-gonadal axis dysfunction, spermatogenesis and maturation disorders, testicular interstitial cell damage erectile dysfunction. Based on the above related mechanisms, a large number of studies have focused on the potential therapeutic association between diabetes progression and infertility in patients with diabetes and infertility, providing important clues for the treatment of this population. In this paper, we summarized the research results of the effects of diabetes on male reproductive function in recent 5 years, elaborated the potential pathophysiological mechanisms of male infertility induced by diabetes, and reviewed and prospected the therapeutic measures.

Ferroptosis boosted oral cancer photodynamic therapy by carrier-free Sorafenib-Ce6 self-assembly nanoparticles.

Oral cancer is a disease with high morbidity and mortality worldwide and greatly impacts the quality of life, especially in patients with advanced stages. Photodynamic therapy (PDT) is one of the most effective clinical treatments for oral cancers. However, most clinically applied photosensitizers have several deficiencies, including oxygen dependence, poor aqueous solubility, and a lack of tumor-targeting ability. Herein, the carrier-free multifunctional Sorafenib (Sor), chlorin e6 (Ce6), and Fe3+ self-assembly co-delivery nanoparticles (Sor-Ce6 NPs) were constructed via combining a ferroptosis inducer Sor and a photosensitizer Ce6 for synergetic therapy. The as-synthesized Sor-Ce6 NPs presented excellent colloidal stability and water dispersity with good in vivo tumor-targeting ability. More significantly, the low dose of Sor-Ce6 NPs had little dark toxicity but produced significantly enhanced ROS and supplied O2 sustainably to increase phototoxicity through ferroptosis pathway. Notably, the Sor-Ce6 NPs showed significantly higher in vitro and in vivo anti-tumor efficacy than the Sor/Ce6 mixture due to the improvement of cellular uptake and the incorporation of foreign Fe ions in the system, which also confer the T1 magnetic resonance-guided imaging ability to the formed Sor-Ce6 NPs. Our study demonstrates a promising self-assembled strategy for overcoming hypoxia-related PDT resistance for oral cancer treatment.