Macrophage iron dyshomeostasis promotes aging-related renal fibrosis.

Renal aging, marked by the accumulation of senescent cells and chronic low-grade inflammation, leads to renal interstitial fibrosis and impaired function. In this study, we investigate the role of macrophages, a key regulator of inflammation, in renal aging by analyzing kidney single-cell RNA sequencing data of C57BL/6J mice from 8 weeks to 24 months. Our findings elucidate the dynamic changes in the proportion of kidney cell types during renal aging and reveal that increased macrophage infiltration contributes to chronic low-grade inflammation, with these macrophages exhibiting senescence and activation of ferroptosis signaling. CellChat analysis indicates enhanced communications between macrophages and tubular cells during aging. Suppressing ferroptosis alleviates macrophage-mediated tubular partial epithelial-mesenchymal transition in vitro, thereby mitigating the expression of fibrosis-related genes. Using SCENIC analysis, we infer Stat1 as a key age-related transcription factor promoting iron dyshomeostasis and ferroptosis in macrophages by regulating the expression of Pcbp1, an iron chaperone protein that inhibits ferroptosis. Furthermore, through virtual screening and molecular docking from a library of anti-aging compounds, we construct a docking model targeting Pcbp1, which indicates that the natural small molecule compound Rutin can suppress macrophage senescence and ferroptosis by preserving Pcbp1. In summary, our study underscores the crucial role of macrophage iron dyshomeostasis and ferroptosis in renal aging. Our results also suggest Pcbp1 as an intervention target in aging-related renal fibrosis and highlight Rutin as a potential therapeutic agent in mitigating age-related renal chronic low-grade inflammation and fibrosis.

Recent Advances in Targeted Therapies for Infantile Hemangiomas.

Targeted therapy for infantile hemangiomas (IHs) has been extensively studied as they can concentrate drugs, increase therapeutic efficacy and reduce drug dosage. Meanwhile, they can extend drug release times, enhance drug stability, decrease dosing frequency, and improve patient compliance. Moreover, carriers made from biocompatible materials reduced drug immunogenicity, minimizing adverse reactions. However, current targeted formulations still face numerous challenges such as the non-absolute safety of carrier materials; the need to further increase drug loading capacity; the limitation of animal hemangioma models in fully replicating the biological properties of human infantile hemangiomas; the establishment of models for deep-seated hemangiomas with high incidence rates; and the development of more specific targets or markers. In this review, we provided a brief overview of the characteristics of IHs and summarized the past decade's advances, advantages, and targeting strategies of targeted drug delivery systems for IHs and discussed their applications in the treatment of IHs. Furthermore, the goal is to provide a reference for further research and application in this field.

The treatment process of a giant phyllodes tumor of the breast: a case report and review of the literature.

Giant phyllodes tumors are rare fibroepithelial tumors that are usually larger than 10 cm in diameter, have rapid tumor growth, and are easily recurrent. They are frequently accompanied by skin necrosis and infection, particularly in malignant phyllodes tumors. This case report presents a 50-year-old woman who presented to the hospital with a huge left breast mass that was ruptured and infected. The patient received anti-infective treatment and underwent mastectomy and skin grafting, which indicated a malignant phyllodes tumor. The tumor was completely excised after a local recurrence in the chest wall 6 months post-surgery. Unfortunately, one year later, the patient pass away due to multiple organ failure. Giant phyllodes tumor management presents challenges to the surgeon. This case is being presented to enhance understanding and treatment of phyllodes tumors, specifically giant malignant phyllodes tumors, with the aim of improving patients' quality of life.

Enzymatic functionalization of decellularized tilapia skin scaffolds with enhanced skin regeneration.

The decellularized tilapia skin (dTS) has gained significant attention as a promising material for tissue regeneration due to its ability to provide unique structural and functional components that support cell growth, adhesion, and proliferation. However, the clinical application of dTS is limited by its low mechanical strength and rapid biodegradability. Herein, we prepare a novel RGD (arginine-glycine-aspartic acid) functionalized dTS scaffold (dTS/RGD) by using transglutaminase (TGase) crosslinking. The developed dTS/RGD scaffold possesses excellent properties, including a medium porosity of ∼59.2%, a suitable degradation rate of approximately 80% over a period of two weeks, and appropriate mechanical strength with a maximum tensile stress of ∼46.36 MPa which is much higher than that of dTS (∼32.23 MPa). These properties make the dTS/RGD scaffold ideal for promoting cell adhesion and proliferation, thereby accelerating skin wound healing in a full-thickness skin defect model. Such an enzymatic cross-linking strategy provides a favorable microenvironment for wound healing and holds great potential for application in skin regeneration engineering.

Pre-treatment risk predictors of valproic acid-induced dyslipidemia in pediatric patients with epilepsy.

Background: Valproic acid (VPA) stands as one of the most frequently prescribed medications in children with newly diagnosed epilepsy. Despite its infrequent adverse effects within therapeutic range, prolonged VPA usage may result in metabolic disturbances including insulin resistance and dyslipidemia. These metabolic dysregulations in childhood are notably linked to heightened cardiovascular risk in adulthood. Therefore, identification and effective management of dyslipidemia in children hold paramount significance. Methods: In this retrospective cohort study, we explored the potential associations between physiological factors, medication situation, biochemical parameters before the first dose of VPA (baseline) and VPA-induced dyslipidemia (VID) in pediatric patients. Binary logistic regression was utilized to construct a predictive model for blood lipid disorders, aiming to identify independent pre-treatment risk factors. Additionally, The Receiver Operating Characteristic (ROC) curve was used to evaluate the performance of the model. Results: Through binary logistic regression analysis, we identified for the first time that direct bilirubin (DBIL) (odds ratios (OR) = 0.511, p = 0.01), duration of medication (OR = 0.357, p = 0.009), serum albumin (ALB) (OR = 0.913, p = 0.043), BMI (OR = 1.140, p = 0.045), and aspartate aminotransferase (AST) (OR = 1.038, p = 0.026) at baseline were independent risk factors for VID in pediatric patients with epilepsy. Notably, the predictive ability of DBIL (AUC = 0.690, p < 0.0001) surpassed that of other individual factors. Furthermore, when combined into a predictive model, incorporating all five risk factors, the predictive capacity significantly increased (AUC = 0.777, p < 0.0001), enabling the forecast of 77.7% of dyslipidemia events. Conclusion: DBIL emerges as the most potent predictor, and in conjunction with the other four factors, can effectively forecast VID in pediatric patients with epilepsy. This insight can guide the formulation of individualized strategies for the clinical administration of VPA in children.

Sensorineural hearing loss and cognitive impairment: three hypotheses.

Sensorineural hearing loss (SNHL) is a category of hearing loss that often leads to difficulty in understanding speech and other sounds. Auditory system dysfunction, including deafness and auditory trauma, results in cognitive deficits via neuroplasticity. Cognitive impairment (CI) refers to an abnormality in the brain's higher intellectual processes related to learning, memory, thinking and judgment that can lead to severe learning and memory deficits. Studies have established a strong correlation between SNHL and CI, but it remains unclear how SNHL contributes to CI. The purpose of this article is to describe three hypotheses regarding this relationship, the mainstream cognitive load hypothesis, the co-morbidity hypothesis, and the sensory deprivation hypothesis, as well as the latest research progress related to each hypothesis.

Quartz-enhanced photoacoustic spectroscopy sensing using trapezoidal- and round-head quartz tuning forks.

In this Letter, two novel, to the best of our knowledge, quartz tuning forks (QTFs) with trapezoidal-head and round-head were designed and adopted for quartz-enhanced photoacoustic spectroscopy (QEPAS) sensing. Based on finite element analysis, a theoretical simulation model was established to optimize the design of QTF. For performance comparison, a reported T-head QTF and a commercial QTF were also investigated. The designed QTFs have decreased resonant frequency (f0) and increased gap between the two prongs of QTF. The experimentally determined f0 of the T-head QTF, trapezoidal-head QTF, and round-head QTF were 8690.69 Hz, 9471.67 Hz, and 9499.28 Hz, respectively. The corresponding quality (Q) factors were measured as 11,142, 11,411, and 11,874. Compared to the commercial QTF, the resonance frequencies of these QTFs have reduced by 73.45%, 71.07%, and 70.99% while maintaining a comparable Q factor to the commercially mature QTF. Methane (CH4) was chosen as the analyte to verify the QTFs' performance. Compared with the commercial QTF, the signal-to-noise ratio (SNR) of the CH4-QEPAS system based on the T-head QTF, trapezoidal-head QTF, and round-head QTF has been improved by 1.75 times, 2.96 times, and 3.26 times, respectively. The performance of the CH4-QEPAS sensor based on the QTF with the best performance of the round-head QTF was investigated in detail. The results indicated that the CH4-QEPAS sensor based on the round-head QTF exhibited an excellent linear concentration response. Furthermore, a minimum detection limit (MDL) of 0.87 ppm can be achieved when the system's average time was 1200 s.

High-sensitivity methane detection based on QEPAS and H-QEPAS technologies combined with a self-designed 8.7 kHz quartz tuning fork.

Methane (CH4) is a greenhouse gas as well as being flammable and explosive. In this manuscript, quartz-enhanced photoacoustic spectroscopy (QEPAS) and heterodyne QEPAS (H-QEPAS) exploring a self-designed quartz tuning fork (QTF) with resonance frequency (f0) of ∼8.7 kHz was utilized to achieve sensitive CH4 detection. Compared with the standard commercial 32.768 kHz QTF, this self-designed QTF with a low f0 and large prong gap has the merits of long energy accumulation time and low optical noise. The strongest line located at 6057.08 cm-1 in the 2v3 overtone band of CH4 was chosen as the target absorption line. A diode laser with a high output power of > 30 mW was utilized as the excitation source. Acoustic micro-resonators (AmRs) were added to the sensor architecture to amplify the intensity of acoustic waves. Compared to the bare QTF, after the addition of AmRs, a signal enhancement of 149-fold and 165-fold were obtained for QEPAS and H-QEPAS systems, respectively. The corresponding minimum detection limits (MDLs) were 711 ppb and 1.06 ppm for QEPAS and H-QEPAS sensors. Furthermore, based on Allan variance analysis the MDLs can be improved to 19 ppb and 27 ppb correspondingly. Compared to the QEPAS sensor, the H-QEPAS sensor shows significantly shorter measurement timeframes, allowing for measuring the gas concentration quickly while simultaneously obtaining f0 of QTF.

Comprehensive Analysis of Fatty Acid Metabolism in Diabetic Nephropathy from the Perspective of Immune Landscapes, Diagnosis and Precise Therapy.

Objective: Diabetic nephropathy (DN) represents the principal cause of end-stage renal diseases worldwide, lacking effective therapies. Fatty acid (FA) serves as the primary energy source in the kidney and its dysregulation is frequently observed in DN. Nevertheless, the roles of FA metabolism in the occurrence and progression of DN have not been fully elucidated. Methods: Three DN datasets (GSE96804/GSE30528/GSE104948) were obtained and combined. Differentially expressed FA metabolism-related genes were identified and subjected to DN classification using "ConsensusClusterPlus". DN subtypes-associated modules were discovered by "WGCNA", and module genes underwent functional enrichment analysis. The immune landscapes and potential drugs were analyzed using "CIBERSORT" and "CMAP", respectively. Candidate diagnostic biomarkers of DN were screened using machine learning algorithms. A prediction model was constructed, and the performance was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The online tool "Nephroseq v5" was conducted to reveal the clinical significance of the candidate diagnostic biomarkers in patients with DN. A DN mouse model was established to verify the biomarkers' expression. Results: According to 39 dysregulated FA metabolism-related genes, DN samples were divided into two molecular subtypes. Patients in Cluster B exhibited worse outcomes with a different immune landscape compared with those in Cluster A. Ten potential small-molecular drugs were predicted to treat DN in Cluster B. The diagnostic model based on PRKAR2B/ANXA1 was created with ideal predictive values in early and advanced stages of DN. The correlation analysis revealed significant association between PRKAR2B/ANXA1 and clinical characteristics. The DN mouse model validated the expression patterns of PRKAR2B/ANXA1. Conclusion: Our study provides new insights into the role of FA metabolism in the classification, immunological pathogenesis, early diagnosis, and precise therapy of DN.

Dual-frequency modulated heterodyne quartz-enhanced photoacoustic spectroscopy.

A novel dual-frequency modulated heterodyne quartz-enhanced photoacoustic spectroscopy (DFH-QEPAS) was demonstrated for what we believe to be the first time in this study. In traditional H-QEPAS, the frequency of modulated sinusoidal wave has a frequency difference (Δf) with the resonance frequency (f0) of a quartz tuning fork (QTF). Owing to the resonance characteristic of QTF, it cannot excite QTF to the strongest response. To achieve a stronger response, a sinusoidal wave with a frequency of f0 was added to the modulation wave to compose a dual-frequency modulation. Acetylene (C2H2) was chosen as the target gas to verify the sensor performance. The proposed DFH-QEPAS improved 4.05 times of signal-to-noise ratio (SNR) compared with the traditional H-QEPAS in the same environmental conditions.

Photoinduced Cobalt Catalyzed Radical Heck-Type Reaction of Alkyl Electrophiles.

We report here a general alkylation reaction of terminal alkenes with nucleophilic cobaloxime complex catalysis under visible light irradiation. A broad range of vinyl arenes and heteroarenes, as well as a diverse set of alkyl(pseudo)halides or strained rings as alkyl electrophiles, can efficiently undergo the transformation up to the gram scale. Mechanistic study reveals the radical nature of the reaction and corroborates our design involving alkylcobaloxime as the key intermediate.

Quercetin-loaded PLGA nanoparticles coating with macrophage membranes for targeted delivery in acute liver injury.

Quercetin (QU), a natural flavonoid with potent anti-inflammatory and antioxidant properties, holds promise in treating acute liver injury (ALI). Nonetheless, its limited solubility hampers its efficacy, and its systemic distribution lacks targeting, leading to off-target effects. To address these challenges, we developed macrophage membrane-coated quercetin-loaded PLGA nanoparticles (MVs-QU-NPs) for active ALI targeting. The resulting MVs-QU-NPs exhibited a spherical morphology with a clear core-shell structure. The average size and zeta potential were assessed as 141.70 ± 0.89 nm and -31.83 ± 0.76 mV, respectively. Further studies revealed sustained drug release characteristics from MVs-QU-NPs over a continuous period of 24 h. Moreover, these MVs-QU-NPs demonstrated excellent biocompatibility when tested on normal liver cells. The results of biodistribution analysis in ALI mice displayed the remarkable ALI-targeting ability of MVs-DiD-NPs, with the highest fluorescence intensity observed in liver tissue. This biomimetic approach combining macrophage membranes with nanoparticle delivery, holds great potential for targeted ALI treatment.

Research progress of calcium carbonate nanomaterials in cancer therapy: challenge and opportunity.

Cancer has keeping the main threat to the health of human being. Its overall survival rate has shown rare substantial progress in spite of the improving diagnostic and treatment techniques for cancer in recent years. Indeed, such classic strategies for malignant tumor as surgery, radiation and chemotherapy have been developed and bring more hope to the patients, but still been accompanied by certain limitations, which include the challenge of managing large wound sizes, systemic toxic side effects, and harmful to the healthy tissues caused by imprecise alignment with tumors in radiotherapy. Furthermore, immunotherapy exhibits a limited therapeutic effect in advanced tumors which is reported only up to 25%-30%. The combination of nanomaterials and cancer treatment offers new hope for cancer patients, demonstrating strong potential in the field of medical research. Among the extensively utilized nanomaterials, calcium carbonate nanomaterials (CCNM) exhibit a broad spectrum of biomedical applications due to their abundant availability, cost-effectiveness, and exceptional safety profile. CCNM have the potential to elevate intracellular Ca2+ levels in tumor cells, trigger the mitochondrial damage and ultimately lead to tumor cell death. Moreover, compared with other types of nanomaterials, CCNM exhibit remarkable advantages as delivery systems owing to their high loading capacity, biocompatibility and biodegradability. The purpose of this review is to provide an overview of CCNM synthesis, focusing on summarizing its diverse roles in cancer treatment and the benefits and challenges associated with CCNM in cancer therapy. Hoping to present the significance of CCNM as for the clinical application, and summarize information for the design of CCNM and other types of nanomaterials in the future.

Spontaneous Otogenic Intracranial Pneumocephalus: A Case Report.

Spontaneous otogenic pneumocephalus (SOP) is a rare condition. We report a case of SOP that may be related to repeated Valsalva maneuvers. A young woman underwent repeated Valsalva maneuvers to restore Eustachian tube function and subsequently developed symptoms that included otalgia, headache, and nausea. A temporal bone computed tomography scan was performed and a diagnosis of SOP was made. Subsequent surgical treatment was performed and no recurrence was found during the 1-year follow-up period. The rarity of SOP and its potential for misdiagnosis pose significant challenges in clinical practice. The Valsalva maneuver is 1 of the contributing factors to this phenomenon. Otologists should be familiar with the potential complications of the Valsalva maneuver and use it with greater caution.

Impact of Long-Term Shaolin Zen Meditation on Emotional Processing in Aging: A Visual ERP Study.

The aging process is always accompanied by a decline in cognitive and emotional functions. Although previous studies have identified the positive effects of different meditative practices on emotional and cognitive functions, few studies have investigated the most primitive Chinese meditation-Shaolin Zen meditation. In particular, data are extremely limited regarding the brain mechanism of the effects of Shaolin Zen meditation on cognitive and emotional functions during aging. The current study aimed to explore the effects of long-term Shaolin Zen meditation practice on event-related potentials (ERPs) during facial emotion recognition in aging. ERPs were recorded from 16 monks with long-term meditation experience and 20 controls without meditation experience. The significant age-related degenerative changes in the early ERP components did not present in the meditators but only in the controls without meditation experience. Additionally, we found no group differences in the late P3 component. These findings suggest that long-term Shaolin Zen meditation practice can counteract the age-related cognitive decline in the "down-top" automatic processing of emotional stimuli.

Disassembling ability of lipopeptide promotes the antibacterial activity.

Lipopeptides have become one of the most potent antibacterial agents, however, there is so far no consensus about the link between their physic-chemical properties and biological activity, in particular their inherent aggregation propensity and antibacterial potency. To this end, we here de novo design a series of lipopeptides (CnH(2n-1)O-(VVKK)2V-NH2), in which an alkyl chain is covalently attached onto the N-terminus of a short cationic peptide sequence with an alternating pattern of hydrophobic VV (Val) and positively charged KK (Lys) motifs. By varying the alkyl chain length (ortho-octanoic acid (C8), lauric acid (C12), and palmitic acid (C16)), the lipopeptides show distinct physicochemical properties and self-assembly behaviors, which have great effect on their antibacterial activities. C8H15O-(VVKK)2V-NH2, which contains the lowest hydrophobicity and surface activity has the lowest antibacterial activity. C12H23O-(VVKK)2V-NH2 and C16H31O-(VVKK)2V-NH2 both have high hydrophobicity and surface activity, and self-assembled into long nanofibers. However, the nanofibers formed by C12H23O-(VVKK)2V-NH2 disassembled by dilution, resulting in its high antibacterial activity via bacterial membrane disruption. Comparatively, the nanofibers formed by C16H31O-(VVKK)2V-NH2 were very stable, which can closely attach on bacterial surface but not permeate bacterial membrane, leading to its low antibacterial activity. Thus, the stability other than the morphologies of lipopeptides' nanostructures contribute to their antibacterial ability. Importantly, this study enhances our understanding of the antibacterial mechanisms of self-assembling lipopeptides that will be helpful in exploring their biomedical applications.

Real-World Safety and Effectiveness of Omalizumab in Moderate to Severe Allergic Asthma Patients in China: A Post-Authorization Study.

Purpose: Omalizumab was first approved in China in 2017 for the treatment of moderate to severe allergic asthma for adult and adolescent patients aged ≥12 years. In accordance with the Chinese Health Authority requirement, the post-authorization safety study (PASS) was conducted to evaluate the safety and effectiveness of omalizumab in a real-world setting in patients with moderate to severe allergic asthma in China over a 24-week observation period. Patients and Methods: This is a single-arm, non-interventional, multicenter, PASS conducted in adult, adolescent, and pediatric patients (≥6 years old) with moderate to severe allergic asthma receiving omalizumab in a real-world clinical setting from 2020 to 2021 in 59 sites of mainland China. Results: In total, 1546 patients were screened and 1528 were enrolled. They were stratified according to age (6 to <12 years [n = 191]; ≥12 years [n = 1336]; unknown [n = 1]). Among the overall population, 23.6% and 4.5% of patients reported adverse events (AEs) and serious adverse events (SAEs), respectively. Among pediatric patients (6 to <12 years), 14.1% and 1.6% patients reported AEs and SAEs, respectively. AEs that led to treatment discontinuation in both age groups were <2%. No new safety signals were reported. Effectiveness results showed improvement in lung function, asthma control, and quality of life (QoL). Conclusion: The findings of the current study demonstrated that the safety profile of omalizumab was consistent with its known profile in allergic asthma, and no new safety signals were reported. Omalizumab treatment was effective in improving the lung function and QoL in patients with allergic asthma.

A Miniaturized 3D-Printed Quartz-Enhanced Photoacoustic Spectroscopy Sensor for Methane Detection with a High-Power Diode Laser.

In this invited paper, a highly sensitive methane (CH4) trace gas sensor based on quartz-enhanced photoacoustic spectroscopy (QEPAS) technique using a high-power diode laser and a miniaturized 3D-printed acoustic detection unit (ADU) is demonstrated for the first time. A high-power diode laser emitting at 6057.10 cm-1 (1650.96 nm), with the optical power up to 38 mW, was selected as the excitation source to provide a strong excitation. A 3D-printed ADU, including the optical and photoacoustic detection elements, had a dimension of 42 mm, 27 mm, and 8 mm in length, width, and height, respectively. The total weight of this 3D-printed ADU, including all elements, was 6 g. A quartz tuning fork (QTF) with a resonant frequency and Q factor of 32.749 kHz and 10,598, respectively, was used as an acoustic transducer. The performance of the high-power diode laser-based CH4-QEPAS sensor, with 3D-printed ADU, was investigated in detail. The optimum laser wavelength modulation depth was found to be 0.302 cm-1. The concentration response of this CH4-QEPAS sensor was researched when the CH4 gas sample, with different concentration samples, was adopted. The obtained results showed that this CH4-QEPAS sensor had an outstanding linear concentration response. The minimum detection limit (MDL) was found to be 14.93 ppm. The normalized noise equivalent absorption (NNEA) coefficient was obtained as 2.20 × 10-7 cm-1W/Hz-1/2. A highly sensitive CH4-QEPAS sensor, with a small volume and light weight of ADU, is advantageous for the real applications. It can be portable and carried on some platforms, such as an unmanned aerial vehicle (UAV) and a balloon.

Amyloid-like aggregates of short self-assembly peptide selectively induce melanoma cell apoptosis.

With the rising global incidence of melanoma, new anti-melanoma drugs with low-inducing drug resistance and high selectivity are in urgent need. Inspired by the physiological events in which fibrillar aggregates formed by amyloid proteins are toxic to normal tissues, we here rationally design a tyrosinase responsive peptide, I4K2Y* (Ac-IIIIKKDopa-NH2). Such peptide self-assembled into long nanofibers outside the cells, while it was catalyzed into amyloid-like aggregates by tyrosinase which was rich in melanoma cells. The newly formed aggregates concentrated around the nucleus of melanoma cells, blocking the exchange of biomolecules between the nucleus and cytoplasm and finally leading to cell apoptosis via the S phase arrest in cell cycle distribution and dysfunction of mitochondria. Furthermore, I4K2Y* effectively inhibited B16 melanoma growth in a mouse model but with minimal side effects. We believe that the strategy of combining the usage of toxic amyloid-like aggregates and in-situ enzymatic reactions by specific enzymes in tumor cells will bring profound implications for designing new anti-tumor drugs with high selectivity.

Pyroptosis and degenerative diseases of the elderly.

Pyroptosis is a recently described mechanism of programmed cell death mediated by proteins of the gasdermin family. Widely recognized signaling cascades include the classical, non-classical, caspase-3-dependent gasdermin E and caspase-8-dependent gasdermin D pathways. Additional pyroptotic pathways have been subsequently reported. With the rising prevalence of advanced age, the role of pyroptosis in the degenerative diseases of the elderly has attracted increased research attention. This article reviews the primary mechanisms of pyroptosis and summarizes progress in the research of degenerative diseases of the elderly such as presbycusis, age-related macular degeneration, Alzheimer's disease, intervertebral disc degeneration, and osteoarthritis.