Single-cell multiomics reveals ENL mutation perturbs kidney developmental trajectory by rewiring gene regulatory landscape.

How disruptions to normal cell differentiation link to tumorigenesis remains incompletely understood. Wilms tumor, an embryonal tumor associated with disrupted organogenesis, often harbors mutations in epigenetic regulators, but their role in kidney development remains unexplored. Here, we show at single-cell resolution that a Wilms tumor-associated mutation in the histone acetylation reader ENL disrupts kidney differentiation in mice by rewiring the gene regulatory landscape. Mutant ENL promotes nephron progenitor commitment while restricting their differentiation by dysregulating transcription factors such as Hox clusters. It also induces abnormal progenitors that lose kidney-associated chromatin identity. Furthermore, mutant ENL alters the transcriptome and chromatin accessibility of stromal progenitors, resulting in hyperactivation of Wnt signaling. The impacts of mutant ENL on both nephron and stroma lineages lead to profound kidney developmental defects and postnatal mortality in mice. Notably, a small molecule inhibiting mutant ENL's histone acetylation binding activity largely reverses these defects. This study provides insights into how mutations in epigenetic regulators disrupt kidney development and suggests a potential therapeutic approach.

Histidine as a versatile excipient in the protein-based biopharmaceutical formulations.

Adequate stabilization is essential for marketed protein-based biopharmaceutical formulations to withstand the various stresses that can be exerted during the pre- and post-manufacturing processes. Therefore, a suitable choice of excipient is a significant step in the manufacturing of such delicate products. Histidine, an essential amino acid, has been extensively used in protein-based biopharmaceutical formulations. The physicochemical properties of histidine are unique among amino acids and could afford multifaceted benefits to protein-based biopharmaceutical formulations. With a pKa of approximately 6.0 at the side chain, histidine has been primarily used as a buffering agent, especially for pH 5.5-6.5. Additionally, histidine exhibited several affirmative properties similar to those of carbohydrates (e.g., sucrose and trehalose) and could therefore be considered to be an alternative approach to established protein-based formulation strategies. The current review describes the general physicochemical properties of histidine, lists all commercial histidine-containing protein-based biopharmaceutical products, and discusses a brief outline of the existing research focused on the versatile applications of histidine, which can act as a buffering agent, stabilizer, cryo/lyo-protectant, antioxidant, viscosity reducer, and solubilizing agent. The interaction between histidine and proteins in protein-based biopharmaceutical formulations, such as the Donnan effect during diafiltration of monoclonal antibody solutions and the degradation of polysorbates in histidine buffer, has also been discussed. As the first review of histidine in protein biopharmaceuticals, it helps to deepen our understanding of the opportunities and challenges associated with histidine as an excipient for protein-based biopharmaceutical formulations.

Development and validation of a novel prediction model for Carbapenem-resistant organism infection in a large-scale hospitalized patients.

Carbapenem-resistant organism (CRO) are defined as gram-negative bacteria. The lack of safe and effective antibiotics has led to an increase in incidence rate. The purpose of this study is to establish and determine a risk nomogram to predict CRO infection in hospitalized patients. Hospitalized patients' information were collected from the electronic medical record system of hospital between January 2019 and December 2022. Based on the inclusion and exclusion criteria, we identified 131390 inpatients who met the criteria for this study. For the training cohort, the area under the curves (AUC) for predicting the CRO infection was 0.935. For the validation cohort, the AUC for predicting the CRO infection was 0.937. We have developed the first novel nomogram to predict CRO infection in hospitalized patients, which is reliable and high-performance. The nomogram performs well among hospitalized patients and has good predictive ability.

Unraveling the function of FGF signaling in human hypoblast specialization.

Dattani et al.1 developed a method for inducing hypoblast-like cells from human naive pluripotent stem cells. They elucidated the requirement for FGF signaling in human hypoblast specialization at a specific time window, which was previously controversial.

Modern perspectives of heavy metals alleviation from oil contaminated soil: A review.

Heavy metal poisoning of soil from oil spills causes serious environmental problems worldwide. Various causes and effects of heavy metal pollution in the soil environment are discussed in this article. In addition, this study explores new approaches to cleaning up soil that has been contaminated with heavy metals as a result of oil spills. Furthermore, it provides a thorough analysis of recent developments in remediation methods, such as novel nano-based approaches, chemical amendments, bioremediation, and phytoremediation. The objective of this review is to provide a comprehensive overview of the removal of heavy metals from oil-contaminated soils. This review emphasizes on the integration of various approaches and the development of hybrid approaches that combine various remediation techniques in a synergistic way to improve sustainability and efficacy. The study places a strong emphasis on each remediation strategy that can be applied in the real-world circumstances while critically evaluating its effectiveness, drawbacks, and environmental repercussions. Additionally, it discusses the processes that reduce heavy metal toxicity and improve soil health, taking into account elements like interactions between plants and microbes, bioavailability, and pollutant uptake pathways. Furthermore, the current study suggests that more research and development is needed in this area, particularly to overcome current barriers, improve our understanding of underlying mechanisms, and investigate cutting-edge ideas that have the potential to completely transform the heavy metal clean up industry.

Knockdown of AMIGO2 suppresses proliferation and migration through regulating PPAR-γ in bladder cancer.

PURPOSE: This study aims to reveal the relationship between AMIGO2 and proliferation, migration and tumorigenicity of bladder cancer, and explore the potential molecular mechanisms. METHODS: The expression level of AMIGO2 is measured by qRT-PCR and immunohistochemistry (IHC). Stable AMIGO2 knockdown cell lines T24 and 5637 were established by lentivirus transfection. Cell Counting Kit (CCK-8 assay) was produced to determine cell proliferation, flow cytometry analysis was utilized to detect cell cycle, and wound healing assay was proceeded to test migration ability of bladder cancer cells. Xenograft mouse model was established for investigating the effect of AMIGO2 on tumor formation in vivo. The RNA Sequencing technology was applied to explore the underlying mechanisms. The expression level of PPAR-γ was measured by Western Blot. RESULTS: AMIGO2 was upregulated in bladder cancer cells and tissues. Inhibited expression of AMIGO2 suppresses cell proliferation and migration. Low AMIGO2 expression inhibited tumorigenicity of 5637 in nude mice. According to RNA-Seq and bioinformatics analysis, 917 DEGs were identified. The DEGs were mainly enriched in cell-cell adhesion, peroxisome proliferators-activated receptors (PPARs) signaling pathway and some other pathways. PPAR-γ is highly expressed in bladder cancer cell lines T24 and 5637, but when AMIGO2 is knocked down in T24 and 5637, the expression level of PPAR-γ is also decreased, and overexpression of PPAR-γ could reverse the suppression effect of cell proliferation and migration caused by the inhibition of AMIGO2. CONCLUSION: AMIGO2 is overexpressed in bladder cancer cells and tissues. Knockdown of AMIGO2 suppresses bladder cancer cell proliferation and migration. These processes might be regulated by PPAR-γ signaling pathway.

Cathepsin S (CTSS) in IgA nephropathy: an exploratory study on its role as a potential diagnostic biomarker and therapeutic target.

Introduction: IgA nephropathy (IgAN), a prevalent form of glomerulonephritis globally, exhibits complex pathogenesis. Cathepsins, cysteine proteases within lysosomes, are implicated in various physiological and pathological processes, including renal conditions. Prior observational studies have suggested a potential link between cathepsins and IgAN, yet the precise causal relationship remains unclear. Methods: We conducted a comprehensive bidirectional and multivariable Mendelian randomization (MR) study using publicly available genetic data to explore the causal association between cathepsins and IgAN systematically. Additionally, immunohistochemical (IHC) staining and enzyme-linked immunosorbent assay (ELISA) were employed to evaluate cathepsin expression levels in renal tissues and serum of IgAN patients. We investigated the underlying mechanisms via gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and immune cell infiltration analysis. Molecular docking and virtual screening were also performed to identify potential drug candidates through drug repositioning. Results: Univariate MR analyses demonstrated a significant link between increased cathepsin S (CTSS) levels and a heightened risk of IgAN. This was evidenced by an odds ratio (OR) of 1.041 (95% CI=1.009-1.073, P=0.012) as estimated using the inverse variance weighting (IVW) method. In multivariable MR analysis, even after adjusting for other cathepsins, elevated CTSS levels continued to show a strong correlation with an increased risk of IgAN (IVW P=0.020, OR=1.037, 95% CI=1.006-1.069). However, reverse MR analyses did not establish a causal relationship between IgAN and various cathepsins. IHC and ELISA findings revealed significant overexpression of CTSS in both renal tissues and serum of IgAN patients compared to controls, and this high expression was unique to IgAN compared with several other primary kidney diseases such as membranous nephropathy, minimal change disease and focal segmental glomerulosclerosis. Investigations into immune cell infiltration, GSEA, and GSVA highlighted the role of CTSS expression in the immune dysregulation observed in IgAN. Molecular docking and virtual screening pinpointed Camostat mesylate, c-Kit-IN-1, and Mocetinostat as the top drug candidates for targeting CTSS. Conclusion: Elevated CTSS levels are associated with an increased risk of IgAN, and this enzyme is notably overexpressed in IgAN patients' serum and renal tissues. CTSS could potentially act as a diagnostic biomarker, providing new avenues for diagnosing and treating IgAN.

CircHIPK2 Contributes Cell Growth in Intestinal Epithelial of Colitis and Colorectal Cancer through Promoting TAZ Translation.

Colorectal cancer (CRC) and inflammatory bowel disease (IBD) are escalating global health concerns. Despite their distinct clinical presentations, both disorders share intricate genetic and molecular interactions. The Hippo signaling pathway plays a crucial role in regulating cell processes and is implicated in the pathogenesis of IBD and CRC. Circular RNAs (circRNAs) have gained attention for their roles in various diseases, including IBD and CRC. However, a comprehensive understanding of specific circRNAs involved in both IBD and CRC, and their functional roles is lacking. Here, it is found that circHIPK2 (hsa_circRNA_104507) is a bona fide circRNA consistently upregulated in both IBD and CRC suggesting its potential as a biomarker. Furthermore, silencing of circHIPK2 suppressed the growth of CRC cells in vitro and in vivo. Interestingly, decreased circHipk2 potentiated dextran sulfate sodium (DSS)-induced colitis but alleviated colitis-associated tumorigenesis. Most significantly, mechanistic investigations further unveil that circHIPK2, mediated by FUS, interacting with EIF4A3 to promote the translation of TAZ, ultimately increasing the transcription of downstream target genes CCN1 and CCN2. Taken together, circHIPK2 emerges as a key player in the shared mechanisms of IBD and CRC, modulating the Hippo signaling pathway. CircHIPK2-EIF4A3 axis contributes to cell growth in intestinal epithelial of colitis and CRC by enhancing TAZ translation.

Rejuvenation of young blood on aging organs: Effects, circulating factors, and mechanisms.

Aging causes degenerative changes in organs, leading to a decline in physical function. Over the past two decades, researchers have made significant progress in understanding the rejuvenating effects of young blood on aging organs, benefiting from heterochronic parabiosis models that connect the blood circulation of aged and young rodents. It has been discovered that young blood can partially rejuvenate organs in old animals by regulating important aging-related signaling pathways. Clinical trials have also shown the effectiveness of young blood in treating aging-related diseases. However, the limited availability of young blood poses a challenge to implementing anti-aging therapies on a large scale for older individuals. As a promising alternative, scientists have identified some specific anti-aging circulating factors in young blood that have been shown to promote organ regeneration, reduce inflammation, and alleviate fibrosis associated with aging in animal experiments. While previous reviews have focused primarily on the effects and mechanisms of circulating factors on aging, it is important to acknowledge that studying the rejuvenating effects and mechanisms of young blood has been a significant source of inspiration in this field, and it will continue to be in the future. In recent years, new findings have emerged, further expanding our knowledge in this area. This review aims to summarize the rejuvenating effects and mechanisms of young blood and circulating factors, discussing their similarities and connections, addressing discrepancies in previous studies, outlining future research directions, and highlighting the potential for clinical translation in anti-aging interventions.

Naoxintong capsule for treating cardiovascular and cerebrovascular diseases: from bench to bedside.

Naoxintong Capsule (NXT), a renowned traditional Chinese medicine (TCM) formulation, has been broadly applied in China for more than 30 years. Over decades, accumulating evidences have proven satisfactory efficacy and safety of NXT in treating cardiovascular and cerebrovascular diseases (CCVD). Studies have been conducted unceasingly, while this growing latest knowledge of NXT has not yet been interpreted properly and summarized comprehensively. Hence, we systematically review the advancements in NXT research, from its chemical constituents, quality control, pharmacokinetics, to its profound pharmacological activities as well as its clinical applications in CCVD. Moreover, we further propose specific challenges for its future perspectives: 1) to precisely clarify bioactivities of single compound in complicated mixtures; 2) to evaluate the pharmacokinetic behaviors of NXT feature components in clinical studies, especially drug-drug interactions in CCVD patients; 3) to explore and validate its multi-target mechanisms by integrating multi-omics technologies; 4) to re-evaluate the safety and efficacy of NXT by carrying out large-scale, multicenter randomized controlled trials. In brief, this review aims to straighten out a paradigm for TCM modernization, which help to contribute NXT as a piece of Chinese Wisdom into the advanced intervention strategy for CCVD therapy.

Biodegradable microspheres come into sight: A promising biomaterial for delivering drug to the posterior segment of the eyeball.

Posterior segment disease acts as a major cause of irreversible visual impairments. Successful treatment of posterior segment disease requires the efficient delivery of therapeutic substances to the targeted lesion. However, the complex ocular architecture makes the bioavailability of topically applied drugs extremely low. Invasive delivery approaches like intravitreal injection may cause adverse complications. To enhance the efficiency, several biomedical engineering systems have been developed to increase the penetration efficiency and improve the bioavailability of drugs at the posterior segments. Advantageously, biodegradable microspheres are found to deliver the therapeutic agents in a controlled fashion. The microspheres prepared from novel biomaterials can realize the prolonged release at the posterior segment with minimum side effects. Moreover, it will be degraded automatically into products that are non-toxic to the human body without the necessity of secondary operation to remove the residual polymer matrix. Additionally, biodegradable microspheres have decent thermoplasticity, adjustable hydrophilicity, controlled crystallinity, and high tensile strength, which make them suitable for intraocular delivery. In this review, we introduce the latest advancements in microsphere production technology and elaborate on the biomaterials that are used to prepare microspheres. We discuss systematically the pharmacological characteristics of biodegradable microspheres and compare their potential advantages and limitations in the treatment of posterior segment diseases. These findings would enrich our knowledge of biodegradable microspheres and cast light into the discovery of effective biomaterials for ocular drug delivery.

Regulatory role of exosome-derived miRNAs and other contents in adipogenesis.

Intramuscular fat (IMF) content significantly impacts meat quality. influenced by complex interactions between skeletal muscle cells and adipocytes. Adipogenesis plays a pivotal role in IMF formation. Exosomes, extracellular membranous nanovesicles, facilitate intercellular communication by transporting proteins, nucleic acids (DNA and RNA), and other biomolecules into target cells, thereby modulating cellular behaviors. Recent studies have linked exosome-derived microRNAs (miRNAs) and other cargo to adipogenic processes. Various cell types, including skeletal muscle cells, interact with adipocytes via exosome secretion and uptake. Exosomes entering adipocytes regulate adipogenesis by modulating key signaling pathways, thereby influencing the extent and distribution of IMF deposition.This review comprehensively explores the origin, formation, and mechanisms of exosome action, along with current research and their applications in adipogenesis. Emphasis is placed on exosome-mediated regulation of miRNAs, non-coding RNAs (ncRNAs), proteins, lipids, and other biomolecules during adipogenesis. Leveraging exosomal contents for genetic breeding and treating obesity-related disorders is discussed. Insights gathered contribute to advancing understanding and potential therapeutic applications of exosome-regulated adipogenesis mechanisms.

Target-Oriented Reference Construction for supervised cell-type identification in scRNA-seq.

Cell-type identification is the most crucial step in single cell RNA-seq (scRNA-seq) data analysis, for which the supervised cell-type identification method is a desired solution due to the accuracy and efficiency. The performance of such methods is highly dependent on the quality of the reference data. Even though there are many supervised cell-type identification tools, there is no method for selecting and constructing reference data. Here we develop Target-Oriented Reference Construction (TORC), a widely applicable strategy for constructing reference given target dataset in scRNA-seq supervised cell-type identification. TORC alleviates the differences in data distribution and cell-type composition between reference and target. Extensive benchmarks on simulated and real data analyses demonstrate consistent improvements in cell-type identification from TORC. TORC is freely available at https://github.com/weix21/TORC.

The association between circulating phenylalanine and the temporal risk of impaired insulin markers in gestational diabetes mellitus.

Background: We aimed to contrast plasma amino acid concentrations in pregnant women with Gestational Diabetes Mellitus (GDM) to those without, to analyze the link between plasma amino acid concentrations, GDM, insulin resistance, and insulin secretion at 24-28 weeks of gestation. Methods: The research employed a retrospective case-control study design at a single center. Basic demographic and laboratory data were procured from the hospital's case system. The study encompassed seventy women without gestational diabetes mellitus (GDM) and thirty-five women with GDM matched in a 1-to-2 ratio for age and pre-pregnancy BMI. Utilizing high-performance liquid chromatography-mass spectrometry (HPLC-MS), peripheral fasting plasma amino acid concentrations in these women, during mid-pregnancy, were duly measured. We carefully evaluated the significant differences in the quantitative data between the two groups and developed linear regression models to assess the independent risk factors affecting insulin resistance and insulin secretion. Results: Significant variations in insulin secretion and resistance levels distinguished GDM Group from the non-GDM group at three distinct time points, alongside relatively elevated serum Glycosylated Hemoglobin (HbA1c) levels. Triglycerides (TG) were also significantly increased in those with GDM during adipocytokine observations. Apart from glutamic acid and glutamine, the concentrations of the remaining 16 amino acids were notably increased in GDM patients, including all branched chain amino acids(BCAAs) and aromatic amino acids(AAAs). Ultimately, it was ascertained that fasting serum phenylalanine levels were independent risk factors affecting insulin resistance index and insulin secretion at various phases. Conclusions: Various fasting serum amino acid levels are markedly increased in patients with GDM, specifically phenylalanine, which may play role in insulin resistance and secretion.

Body composition characteristics and influencing factors of different parts of sarcopenia in elderly people: A community-based cross-sectional survey.

Objectives: This study aims to describe the differences in body composition among different body parts of the elderly in the community and its relationship with sarcopenia. Methods: Elderly people aged ≥65 underwent bioelectric impedance analysis testing and were categorized into a sarcopenia group, possible sarcopenia group, and control group. The characteristics of body composition indicators in different parts and their relationship with different stages of sarcopenia were analyzed. Results: The sarcopenia group illustrated the lowest values of FFM, FFM%, BFM, BFM%, ICW, and limb PhA, along with higher ECW/TBW in the trunk and left leg compared to the control group. The possible sarcopenia group showed lower FFM% in limbs and trunk, and higher BFM% compared to the control group. Gender differences in elderly body composition were observed, with an increase in BFM% in various body parts posing a risk factor for possible sarcopenia in elderly males, whereas an increase in BFM% except in the left arm was a protective factor for sarcopenia in elderly females. Conclusion: The body composition of the elderly in the community varied significantly in different stages of sarcopenia and genders, which correlated with sarcopenia.

DP-MP: a novel cross-subject fatigue detection framework with DANN-based prototypical representation and mix-up pairwise learning.

OBJECTIVE: Electroencephalography (EEG) is widely recognized as an effective method for detecting fatigue. However, practical applications of EEG for fatigue detection in real-world scenarios are often challenging, particularly in cases involving subjects not included in the training datasets, owing to bio-individual differences and noisy labels. This study aims to develop an effective framework for cross-subject fatigue detection by addressing these challenges. APPROACH: In this study, we propose a novel framework, termed DP-MP, for cross-subject fatigue detection, which utilizes a Domain-Adversarial Neural Network (DANN)-based prototypical representation in conjunction with Mix-up pairwise learning. Our proposed DP-MP framework aims to mitigate the impact of bio-individual differences by encoding fatigue-related semantic structures within EEG signals and exploring shared fatigue prototype features across individuals. Notably, to the best of our knowledge, this work is the first to conceptualize fatigue detection as a pairwise learning task, thereby effectively reducing the interference from noisy labels. Furthermore, we propose the Mix-up pairwise learning (MixPa) approach in the field of fatigue detection, which broadens the advantages of pairwise learning by introducing more diverse and informative relationships among samples. RESULTS: Cross-subject experiments were conducted on two benchmark databases, SEED-VIG and FTEF, achieving state-of-the-art performance with average accuracies of 88.14% and 97.41%, respectively. These promising results demonstrate our model's effectiveness and excellent generalization capability. SIGNIFICANCE: This is the first time EEG-based fatigue detection has been conceptualized as a pairwise learning task, offering a novel perspective to this field. Moreover, our proposed DP-MP framework effectively tackles the challenges of bio-individual differences and noisy labels in the fatigue detection field and demonstrates superior performance. Our work provides valuable insights for future research, promoting the application of brain-computer interfaces for fatigue detection in real-world scenarios. .

Single-cell sequencing reveals the transcriptional alternations of 17ß-estradiol suppressing primordial follicle formation in neonatal mouse ovaries.

Estrogen has been implicated in multiple biological processes, but the variation underlying estrogen-mediated primordial follicle (PF) formation remains unclear. Here, we show that 17ß-estradiol (E2) treatment of neonatal mice led to the inhibition of PF formation and cell proliferation. Single-cell RNA sequencing (scRNA-seq) revealed that E2 treatment caused significant changes in the transcriptome of oocytes and somatic cells. E2 treatment disrupted the synchronised development of oocytes, pre-granulosa (PG) cells and stromal cells. Mechanistically, E2 treatment disrupted several signalling pathways critical to PF formation, especially down-regulating the Kitl and Smad1/3/4/5/7 expression, reducing the frequency and number of cell communication. In addition, E2 treatment influenced key gene expression, mitochondrial function of oocytes, the recruitment and maintenance of PG cells, the cell proliferation of somatic cells, as well as disordered the ovarian microenvironment. This study not only revealed insights into the regulatory role of estrogen during PF formation, but also filled in knowledge of dramatic changes in perinatal hormones, which are critical for the physiological significance of understanding hormone changes and reproductive protection.

Recent advances of biocompatible optical nanobiosensors in liquid biopsy: towards early non-invasive diagnosis.

Liquid biopsy is a non-invasive diagnostic method that can reduce the risk of complications and offers exceptional benefits in the dynamic monitoring and acquisition of heterogeneous cell population information. Optical nanomaterials with excellent light absorption, luminescence, and photoelectrochemical properties have accelerated the development of liquid biopsy technologies. Owing to the unique size effect of optical nanomaterials, their improved optical properties enable them to exhibit good sensitivity and specificity for mitigating signal interference from various molecules in body fluids. Nanomaterials with biocompatible and optical sensing properties play a crucial role in advancing the maturity and diversification of liquid biopsy technologies. This article offers a comprehensive review of recent advanced liquid biopsy technologies that utilize novel biocompatible optical nanomaterials, including fluorescence, colorimetric, photoelectrochemical, and Raman broad-spectrum-based biosensors. We focused on liquid biopsy for the most significant early biomarkers in clinical medicine, and specifically reviewed reports on the effectiveness of optical nanosensing technology in the detection of real patient samples, which may provide basic evidence for the transition of optical nanosensing technology from engineering design to clinical practice. Furthermore, we introduced the integration of optical nanosensing-based liquid biopsy with modern devices, such as smartphones, to demonstrate the potential of the technology in portable clinical diagnosis.

N-Phenyl-2-Pyridone-Derived Endoperoxide Suppressing both Lung Cancer and Idiopathic Pulmonary Fibrosis Progression by Three-Pronged Action.

We report an endoperoxide compound (E5) which can deliver three therapeutic components by a thermal cycloreversion, namely, singlet oxygen, triplet oxygen and 3-methyl-N-phenyl-2-pyridone, thus targeting multiple mechanisms for treating non-small cell lung cancer and idiopathic pulmonary fibrosis. In aqueous environment, E5 undergoes clean reaction to afford three therapeutic components with a half-life of 8.3 hours without the generation of other by-products, which not only achieves good cytotoxicity toward lung cancer cells and decreases the levels of HIF-1α protein, but also inhibits the TGF-ß1 induced fibrosis in vitro. In vivo experiments also demonstrated the efficacy of E5 in inhibiting tumor growth and relieving idiopathic pulmonary fibrosis, while exhibiting good biocompatibility. Many lines of evidence reveal the therapeutic efficacy of singlet oxygen and 3-methyl-N-phenyl-2-pyridone, and triplet oxygen could downregulate HIF-1α and relieve tumor hypoxia which is a critical issue in conventional PDT. Unlike other combination therapies, in which multiple therapeutic agents are given in independent formulations, our work demonstrates single molecule endoperoxide prodrugs could be developed as new platforms for treatment of cancers and related diseases.

Different humidity environments do not affect the subsequent exercise ability of college football players after aerobic high-intensity interval training.

Previous studies have explored the effect of differing heat and relative humidity (RH) environments on the performance of multiple anaerobic high-intensity interval training (HIIT). Still, its impact on physiological responses and performance following aerobic HIIT has not been well studied. This study examined the effects of differing RH environments on physiological responses and performance in college football players following HIIT. Twelve college football completed HIIT under four different environmental conditions: (1) 25 °C/20% RH (Control group); (2) 35 °C/20% RH (H20 group); (3) 35 °C/40% RH (H40 group); (4) 35 °C/80% RH (H80 group). The heart rate (HR), mean arterial pressure (MAP), lactate, tympanic temperature (TT), skin temperature (TS), thermal sensation (TS), and rating of perceived exertion (RPE) were recorded continuously throughout the exercise. The heart rate variability (HRV): including root mean squared differences of the standard deviation (RMSSD)、standard deviation differences of the standard deviation (SDNN)、high frequency (HF), low frequency (LF), squat jump height (SJH), cycling time to exhaustion (TTE), and sweat rate (SR) were monitored pre-exercise and post-exercise. The HR, MAP, lactate, TT, Ts, TS, and RPE in the 4 groups showed a trend of rapid increase, then decreased gradually. There was no significant difference in HR, MAP, TT, or RPE between the 4 groups at the same time point (p > 0.05), in addition to this, when compared to the C group, the lactate, Ts, TS in the other 3 groups significant differences were observed at the corresponding time points (p < 0.05). The RMSSD, SDNN, HF, and LF levels in the 4 groups before exercise were not significantly different. The RMSSD and HF in the H40 and H80 groups were significantly decreased and other HRV indicators showed no significant difference after exercise. In sports performance measurement, the SJH and TTE were significantly decreased, but there was no significant difference in the 4 groups. The SR was no significant difference in the 4 groups after exercise. In conclusion, heat and humidity environments elicited generally greater physiological effects compared with the normal environment but did not affect sports performance in college football players.