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.

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.

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.

Linc279227 contributes to mitochondrial dysfunction in high glucose-treated mouse renal tubular epithelial cells.

BACKGROUND: The aberrant expression of long noncoding RNAs (lncRNAs) has been associated with diabetic nephropathy (DN), a major complication of diabetes mellitus (DM). This study investigated the differential expression of lncRNAs in DM without renal damage and DM with renal damage, known as DN, and elucidated the functions of a pathogenic lncRNA. METHODS: High-throughput sequencing was performed on the kidneys of male db/db mice with kidney injury, db/db mice without kidney involvement and db/m control littermates. Linc279227 expression was confirmed by RT‒qPCR and fluorescence in situ hybridization. The effects of linc279227 on high glucose (HG)-treated renal tubular epithelial cells (RTECs) were evaluated by autophagy flux monitoring, Western blot determination and mitochondrial morphological detection. RESULTS: With high-throughput sequencing, we identified a 1024 nt long intergenic noncoding RNA, TCONS_00279227 (linc279227), whose expression was markedly increased in the kidneys of db/db mice with kidney injury compared to db/db mice without kidney injury and db/m control littermates. Fluorescence in situ hybridization confirmed that linc279227 was mainly located in the renal tubules of mice with DN. In vitro, linc279227 expression was found to be significantly increased in RTECs treated with high glucose (HG) for 48 h. Silencing linc279227 markedly restored the levels of autophagy-/mitophagy-associated proteins in HG-stimulated RTECs. Furthermore, silencing linc279227 reduced phosphorylated Drp1 expression and increased Mfn2 expression in RTECs exposed to HG. CONCLUSION: Our data suggest that linc279227 plays an important role in mitochondrial dysfunction in HG-treated RTECs and that silencing linc279227 rescues RTECs exposed to HG.

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.

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.

Highly Sensitive Trace Gas Detection Based on In-Plane Single-Quartz-Enhanced Dual Spectroscopy.

For this invited manuscript, an in-plane single-quartz-enhanced dual spectroscopy (IP-SQEDS)-based trace gas sensor was demonstrated for the first time. A single quartz tuning fork (QTF) was employed to combine in-plane quartz-enhanced photoacoustic spectroscopy (IP-QEPAS) with light-induced thermoelastic spectroscopy (LITES) techniques. Water vapor (H2O) was chosen as the target gas. Compared to traditional QEPAS, IP-SQEDS not only allowed for simple structures, but also obtained nearly three times signal amplitude enhancement.

Comparative Analysis of Acanthopanacis Cortex and Periplocae Cortex Using an Electronic Nose and Gas Chromatography-Mass Spectrometry Coupled with Multivariate Statistical Analysis.

Chinese Herbal Medicines (CHMs) can be identified by experts according to their odors. However, the identification of these medicines is subjective and requires long-term experience. The samples of Acanthopanacis Cortex and Periplocae Cortex used were dried cortexes, which are often confused in the market due to their similar appearance, but their chemical composition and odor are different. The clinical use of the two herbs is different, but the phenomenon of being confused with each other often occurs. Therefore, we used an electronic nose (E-nose) to explore the differences in odor information between the two species for fast and robust discrimination, in order to provide a scientific basis for avoiding confusion and misuse in the process of production, circulation and clinical use. In this study, the odor and volatile components of these two medicinal materials were detected by the E-nose and by gas chromatography-mass spectrometry (GC-MS), respectively. An E-nose combined with pattern analysis methods such as principal component analysis (PCA) and partial least squares (PLS) was used to discriminate the cortex samples. The E-nose was used to determine the odors of the samples and enable rapid differentiation of Acanthopanacis Cortex and Periplocae Cortex. GC-MS was utilized to reveal the differences between the volatile constituents of Acanthopanacis Cortex and Periplocae Cortex. In all, 82 components including 9 co-contained components were extracted by chromatographic peak integration and matching, and 24 constituents could be used as chemical markers to distinguish these two species. The E-nose detection technology is able to discriminate between Acanthopanacis Cortex and Periplocae Cortex, with GC-MS providing support to determine the material basis of the E-nose sensors' response. The proposed method is rapid, simple, eco-friendly and can successfully differentiate these two medicinal materials by their odors. It can be applied to quality control links such as online detection, and also provide reference for the establishment of other rapid detection methods. The further development and utilization of this technology is conducive to the further supervision of the quality of CHMs and the healthy development of the industry.

HDAC6-mediated α-tubulin deacetylation suppresses autophagy and enhances motility of podocytes in diabetic nephropathy.

Histone deacetylase 6 (HDAC6) is the specific subtype of HDACs which preferentially located in the cytoplasm, and is crucial in insulin signalling. However, the role of HDAC6 in type 2 diabetic nephropathy (DN) remains undefined. In current study, we observed that HDAC6 was markedly activated in the kidneys of type 2 diabetic patients and db/db mice with albuminuria, along with the advanced glycation end products (AGE)-treated podocytes. Selective inhibition of HDAC6 activity protected kidneys from hyperglycaemia in db/db mice. Notably, overexpressing HDAC6 inhibited autophagy and promoted motility aside from the apoptosis of podocytes exposed to AGE. We further determined that HDAC6 regulated the autophagy partially by decreasing the acetylation of α-tubulin at the residue of lysine 40. In contrast, we confirmed that there was no interaction of HDAC6 with α-tubulin at the sites of lysine 112 and lysine 352. Consistently, inhibiting HDAC6 by siRNA or the selective inhibitor, tubacin, restored the autophagy level and motility of podocytes and rescued podocytes from AGE stimulation. We provide strong evidence of an unexpected role of HDAC6 in the cascade that modulates podocytes autophagy and motility, enlightening that HDAC6 may be a promising therapeutic target for DN treatment.

[Analysis of survey data of popularization of traditional Chinese medicine health culture knowledge in 2017].

To continuously track and analyze the popularization and change trend of traditional Chinese medicine(TCM) health culture knowledge, so as to provide scientific basis for formulating relevant policies, strategies and measures for popularizing Chinese medicine health culture knowledge. In this study, PPS combined with random sampling method was used to survey residents aged between 15 and 69 in 328 survey sites in 30 provinces, autonomous regions and municipalities(excluding Tibet Autonomous Region, Hong Kong, Macao and Taiwan). In the study, a standardized questionnaire was used to survey the contact, cognition, trust and use of Chinese medicine health culture knowledge. A total of 89 107 people were respondent in this study, including 87 287 valid questionnaires, with an effective rate of 97.96%. Among them, the urban residents accounted for 51.35%, rural residents accounted for 48.65%; males took up 48.25%, and females took up 51.75%. In 2017, the national Chinese medicine health culture knowledge popularization rate was 91.72%, the reading rate was 89.61%, the trust rate was 89.60%, and the action rate was 55.53%. The study found that TCM health culture knowledge was more popular among young people, high-education residents and non-sickness groups. It is recommended to strengthen the popularization of traditional Chinese medicine in key areas and key populations, provide differentiated Chinese medicine health education to population in different areas, and cooperation with mass media to provide diversified contents and forms.

[Analysis of knowledge acquisition behavior of traditional Chinese medicine based on internet].

The study aims at understanding the situation of Chinese residents' access to Chinese medicine health culture knowledge through the Internet and analyze its influencing factors. A multi-stage PPS sampling method was used to collect 90 720 people for questionnaire survey. The survey found thatthe probability of Chinese residents accessing Chinese medicine health culture knowledge through the Internet was 54.7%. The females(with the males as reference, OR=1.076, 95% CI 1.018-1.137) and central population(with the east as reference, OR=1.235, 95% CI 1.048-1.456), people with Chinese medicine health culture literacy(with the people who do not have Chinese medicine health culture literacy as reference, OR=2.363, 95% CI 1.976-2.827) had a higher probability of acquiring Chinese medicine health culture knowledge through the Internet. Referring to people who were illiterate or less literate,the OR values of people who went to elementary school, junior school, high school/vocational/technical school and junior college/university was 2.396(95% CI 2.062-2.784),4.481(95% CI 3.751-5.352), 6.687(95% CI 5.541-8.07),and 9.109(95% CI 7.385-11.235). The higher the age, the lower the probability of acquiring Chinese medicine health culture knowledge through the Internet. Taking civil servants as a reference, teachers, students, farmers, and workers had a low probability of acquiring Chinese medicine health culture knowledge through the Internet. The OR values was 0.736(95% CI 0.548-0.988),0.609(95% CI 0.449-0.826), 0.424(95% CI 0.325-0.554),and 0.707(95% CI 0.539-0.927). Regions, gender, age, education level, occupation, and possession of Chinese medicine health culture literacy are factors influencing whether residents obtain Chinese medicine health culture knowledge through the Internet.

[Analysis of Chinese citizens' traditional Chinese medicine health culture literacy level and its influence factors in 2017].

To analyze the TCM health culture level and influence factors of Chinese citizens in 2017. PPS sampling combined with random sampling was used to select the residents aged between 15-69 years old in 30 provinces as the respondents,and a questionnaire study was conducted to investigate their TCM health culture level. In 2017,there were 87 287 valid questionnaires for Chinese citizens' TCM health culture level,including 48. 25% male and 51. 75% female,with a sex ratio of 1 ∶ 1. 073. In 2017,the overall TCM health culture level was 13. 39%,specifically 18. 77% for the urban areas and 10. 51% for the rural areas. Compared with people who were illiterate or less literate,people with an educational background of elementary school,junior high school,high school/vocational/technical school and junior college/university had a higher TCM health culture level,and the OR values were 1. 584( 95% CI[1. 166,2. 152]),2. 827( 95%CI[1. 839,4. 345]),5. 651( 95%CI[3. 637,8. 781]),9. 785( 95%CI[6. 187,15. 477]) in order. With civil servants as the reference,medical workers had a higher TCM health culture level( OR = 1. 829,95%CI[1. 279,2. 616]),while farmers had the lowest TCM health culture level( OR = 0. 493,95% CI[0. 349,0. 697]). Compared with people with the annual household income per capita of 20 000 yuan and below,people with the annual household income per capita between 20 000-50 000,50 000-80 000,80 000 yuan or above had a higher TCM health culture level,and the OR values were 1. 176( 95% CI[0. 963,1. 437]),1. 458( 95%CI[1. 168,1. 820]) and 1. 930( 95%CI[1. 509,2. 469]). Based on the differences between urban and rural areas,the influence factors of citizens' TCM health culture level include education,occupation and income.

Podocyte-specific knockin of PTEN protects kidney from hyperglycemia.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) has proven to be downregulated in podocytes challenged with high glucose (HG), and knockout of PTEN in podocytes aggravated the progression of diabetic kidney disease (DKD). However, whether podocyte-specific knockin of PTEN protects the kidney against hyperglycemia in vivo remains unknown. The inducible podocyte-specific PTEN knockin (PPKI) mice were generated by crossing newly created transgenic loxP-stop- loxP-PTEN mice with podocin-iCreERT2 mice. Diabetes mellitus was induced in mice by intraperitoneal injection of streptozotocin at a dose of 150 mg/kg. In vitro, small interfering RNA and adenovirus interference were used to observe the role of PTEN in HG-treated podocytes. Our data demonstrated that PTEN was markedly reduced in the podocytes of patients with DKD and focal segmental glomerulosclerosis, as well as in those of db/db mice. Interestingly, podocyte-specific knockin of PTEN significantly alleviated albuminuria, mesangial matrix expansion, effacement of podocyte foot processes, and incrassation of glomerular basement membrane in diabetic PPKI mice compared with wild-type diabetic mice, whereas no alteration was observed in the level of blood glucose. The potential renal protection of overexpressed PTEN in podocytes was partly attributed with an improvement in autophagy and motility and the inhibition of apoptosis. Our results showed that podocyte-specific knockin of PTEN protected the kidney against hyperglycemia in vivo , suggesting that targeting PTEN might be a novel and promising therapeutic strategy against DKD.

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.

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.

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.

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.

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.

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.

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.