Analysis of the impact of temperature on the spectral shift in ultraviolet hyperspectral imaging spectrometers.

The imaging spectrometer's high performance in practical applications may be compromised by environmental factors, particularly temperature variations, posing a challenge to its stability. Temperature fluctuations can induce spectral shift, directly impacting the accuracy of spectral measurements, subsequently influencing the precision of radiometric measurements. To address this issue, this study investigates a dual-channel UV imaging spectrometer. This instrument boasts a wavelength calibration accuracy of 0.01 nm. This paper conducts an in-depth analysis of the various mechanisms through which temperature changes influence the spectral line offset in the imaging spectrometer, integrating actual orbital temperature data to discuss the instrument's temperature load settings. The impact of temperature on spectral shift is examined using finite element analysis and optical design software. Estimations of spectral shift were made based on temperature variations. Simulation results indicated that the maximum deviation of spectral shift is estimated at 0.018 nm under a temperature condition of 16 ± 1°C. Under a more controlled orbital temperature condition (16 ± 0.3°C), the maximum deviation of spectral shift decreased to 0.01 nm. Experimental data revealed that at 16 ± 1°C, the maximum deviation of spectral shift did not exceed 0.01 nm. This effectively corroborates our theoretical analysis. The relationship between temperature and spectral shift offers a crucial theoretical foundation for calibrating spectral measurements and managing the thermal conditions of the instrument.

Sea Cucumber Plasmalogen Regulates the Lipid Profile in High-Fat Diet Mouse Liver via Lipophagy.

The sea cucumber plasmalogen PlsEtn has been shown to be associated with various chronic diseases related to lipid metabolism. However, the mechanism is unclear. Therefore, the present study used the sea cucumber plasmanylcholine PakCho as a structural contrast to PlsEtn and assessed its effect in 8 week high-fat diet (HFD)-fed mice. The lipidomic approach based on high-resolution mass spectrometry combined with molecular biology techniques was used to evaluate the mechanism of PlsEtn. The results showed that both PlsEtn and PakCho significantly inhibited an increase in mouse body weight and liver total triglyceride and total cholesterol levels caused by HFD. In addition, oil red O staining demonstrated that lipid droplets stored in the liver were degraded. Meanwhile, untargeted lipidomic experiments revealed that total lipids (increased by 42.8 mmol/mg prot; p < 0.05), triglycerides (increased by 38.9 mmol/mg prot; p < 0.01), sphingolipids (increased by 1.5 mmol/mg prot; p < 0.0001), and phospholipids (increased by 2.5 mmol/mg prot; p < 0.05) were all significantly elevated under HFD. PlsEtn resolved lipid metabolism disorders by alleviating the abnormal expression of lipid subclasses. In addition, five lipid molecular species, PE (18:1/20:4), PE (18:1/20:3), PE (18:1/18:3), TG (16:0/16:0/17:0), and TG (15:0/16:0/18:1), were identified as the biomarkers of HFD-induced lipid metabolism disorders. Finally, lipophagy-associated protein expression analysis showed that HFD abnormally activated lipophagy via ULK1 phosphorylation and PlsEtn alleviated lipophagy disorder through lysosomal function promotion. In addition, PlsEtn performed better than PakCho. Taken together, the current study results unraveled the mechanism of PlsEtn in alleviating lipid metabolism disorder and offered a new theoretical foundation for the high-value development of sea cucumber.

Sea cucumber plasmalogen enhance lipophagy to alleviate abnormal lipid accumulation induced by high-fat diet.

Sea cucumber phospholipids, including the plasmalogen (PlsEtn) and plasmanylcholine (PakCho), have been shown to play a regulatory role in lipid metabolism disorders, but their mechanism of action remains unclear. Therefore, high-fat diet (HFD) and palmitic acid were used to establish lipid accumulation models in mice and HepG2 cells, respectively. Results showed that PlsEtn can reduce lipid deposition both in vivo and in vitro. HFD stimulation abnormally activated lipophagy through the phosphorylation of the AMPK/ULK1 pathway. The lipophagy flux monitor revealed abnormalities in the fusion stage of lipophagy. Of note, only PlsEtn stimulated the dynamic remodeling of the autophagosome membrane, which was indicated by the significantly decreased LC3 II/I ratio and p62 level. In all experiments, the effect of PlsEtn was significantly higher than that of PakCho. These findings elucidated the mechanism of PlsEtn in alleviating lipid accumulation, showed that it might be a lipophagy enhancer, and provided new insights into the high-value utilization of sea cucumber as an agricultural resource.

Water-compatible cross-linked pyrrolidone acrylate pressure-sensitive adhesives with persistent adhesion for transdermal delivery: Synergistic effect of hydrogen bonding and electrostatic force.

Poor skin adhesion and mechanical properties are common problems of pressure-sensitive adhesive (PSA) in transdermal drug delivery system (TDDS). Its poor water compatibility also causes the patch to fall off after sweating or soaking in the application site. To solve this problem, poly (2-Ethylhexyl acrylate-co-N-Vinyl-2-pyrrolidone-co-N-(2-Hydroxyethyl)acrylamide) (PENH), a cross-linked pyrrolidone polyacrylate PSA, was designed to improve the adhesion and water resistance of PSA through electrostatic force and hydrogen bonding system. The structure of PENH was characterized by 1H NMR, FTIR, DSC, and other methods. The mechanism was studied by FTIR, rheological test, and molecular simulation. The results showed that the PENH patch could adhere to human skin for more than 10 days without cold flow, and it could still adhere after sweating or water contact. In contrast, the commercial PSA Duro-Tak® 87-4098 and Duro-Tak® 87-2852 fell off completely on the 3rd and 6th day, respectively, and Duro-Tak® 87-2510 showed a significant dark ring on the second day. Mechanism studies have shown that the hydrogen bond formed by 2-ethylhexyl acrylate (2-EHA), N-vinyl-2-pyrrolidinone (NVP), and N-(2-Hydroxyethyl)acrylamide (HEAA) enhances cohesion, the interaction with skin improves skin adhesion, and the electrostatic interaction with water or drug molecules enhances the ability of water absorption and drug loading. Due to the synergistic effect of hydrogen bonds and electrostatic force, PENH can maintain high cohesion after drug loading or water absorption. PENH provides a choice for the development of water-compatible patches with long-lasting adhesion. STATEMENT OF SIGNIFICANCE: Based on the synergistic effect of hydrogen bonding and electrostatic force, a hydrogen-bonded, cross-linked pyrrolidone acrylate pressure-sensitive adhesive for transdermal drug delivery was designed and synthesized, which has high adhesion and cohesive strength and is non-irritating to the skin. The patch can be applied on the skin surface continuously for more than 10 days without the phenomenon of "dark ring", and the patch can remain adherent after the patient sweats or bathes. This provides a good strategy for choosing a matrix for patches that require prolonged administration.

Association of depressive symptoms with cardiovascular events and plasma BNP: A prospective cohort study of the elderly Chinese population.

OBJECTIVE: To estimate the prevalence of depressive symptoms and to evaluate the associations of mild and significant depressive symptoms with cardiovascular events and plasma BNP levels (which are surrogate endpoints for cardiovascular events) among older adults in a population-based study. METHODS: A population-based prospective study of 1,432 elderly people (aged 70-84 years and without cardiovascular disease) was conducted, and the median duration of follow-up for participants with outcomes was 18 weeks. Depressive symptoms were assessed with the 15-item Geriatric Depression Scale (GDS-15). The hazard ratios (HRs) for the time to events and time to death were calculated using the Cox regression analysis. Multiple linear regression models and Spearman rank correlations were used to examine the association of depressive symptoms with Log BNP values. RESULTS: The prevalence of mild (GDS-15 scores ≥ 6) and significant (GDS-15 scores ≥ 10) depressive symptoms were 7.3% and 2.0% at baseline, respectively. Older adults with significant depressive symptoms exhibited increased risks of time to death (HR: 12.56; 95% CI: 3.58-43.99) and composite cardiovascular endpoints (HR: 3.46; 95% CI: 1.19-3.75). Significant depressive symptoms were associated with Log BNP levels (ß=0.56, P = 0.02). Depressive symptom scores were also associated with Log BNP levels (rs=0.21, P = 0.04) in the older adults with depressive symptoms. CONCLUSIONS: Significant depressive symptoms were associated with a higher risk of cardiovascular events and higher BNP levels in the elderly.

[Early effectiveness of arthroscopic tri-anchor double-pulley suture-bridge repair of medium-size supraspinatus tendon tears].

Objective: To explore the early effectiveness of arthroscopic tri-anchor double-pulley suture-bridge in treatment of medium-size supraspinatus tendon tears. Methods: Between December 2020 and January 2023, 40 patients with medium-size supraspinatus tendon tears were treated with arthroscopic tri-anchor double-pulley suture-bridge. There were 18 males and 22 females, with an average age of 62.6 years (mean, 45-73 years). Among them, 17 patients had trauma history. The main clinical symptom was shoulder pain with hug resistance test (+). The interval from symptom onset to operation was 10.7 months on average (range, 3-36 months). Visual analogue scale (VAS) score, University of California Los Angeles (UCLA) score, American Shoulder and Elbow Surgeons (ASES) score, and shoulder range of motion (ROM) of forward flexion, abduction, and external rotation were used to evaluate shoulder function. MRI was performed to assess the structural integrity and tension of reattached tendon. Patient satisfactions were calculated at last follow-up. Results: All incisions healed by first intention, no complications such as incision infection or nerve injury occurred. All patients were followed up 12-37 months (mean, 18.2 months). At 12 months after operation, VAS score, UCLA score, and ASES score significantly improved when compared with the preoperative scores ( P<0.05). At 3 and 12 months after operation, the ROM of external rotation significantly improved when compared with preoperative one ( P<0.05), and further improved at 12 months after operation ( P<0.05). However, the ROMs of abduction and forward flexion did not improve at 3 months after operation when compared with those before operation ( P>0.05), but significantly improved at 12 months after operation ( P<0.05). Twenty-six patients underwent MRI at 3-6 months, of which 23 patients possessed intact structural integrity, good tendon tension, and tendon healing; 3 patients underwent tendon re-tear. The self-rated satisfaction rate was 92.5% at last follow-up. Conclusion: Arthroscopic tri-anchor double-pulley suture-bridge in treatment of medium-size supraspinatus tendon tears can maximize the tendon-bone contact area, obtain satisfied early effectiveness with high satisfaction rate and low incidence of tendon re-tear. However, the function of abduction is limited at 3 months after operation, and patients need to adhere to rehabilitation training to further improve the joint activity.

[Research progress on distal interlocking screws of cephalomedullary nails in intertrochanteric fractures].

Objective: To summarize the new research progress in distal interlocking screws of cephalomedullary nails for the treatment of intertrochanteric fractures. Methods: Relevant domestic and foreign literature was extensively reviewed to summarize the static/dynamic types of distal interlocking screw holes, biomechanical studies, clinical studies and application principles, effects on toggling in the cavity, and related complications of distal interlocking screws. Results: The mode of the distal interlocking screw holes can be divided into static and dynamic. Distal interlocking screws play the role of anti-rotation, maintaining femur length, resisting compression stress, increasing torque stiffness, resisting varus stress, etc. The number of the screws directly affects the toggling of the main nail in the cavity. At present, regardless of whether long or short nails are used, distal interlocking screws are routinely inserted in clinical practice. However, using distal interlocking screws can significantly increase the duration of anesthesia and operation, increase fluoroscopy exposure time, surgical blood loss, and incision length. There is a trend of trying not to use distal interlocking screws in recent years. No significant difference is found in some studies between the effectiveness of dynamic and static interlocking for AO/Orthopaedic Trauma Association (AO/OTA) 31-A1/2 fractures. At present, the selection of the number and mode of distal interlocking screws is still controversial. When inserting distal interlocking screws, orthopedists should endeavor to minimize the occurrence of complications concerning miss shot, vascular injuries, local stress stimulation, and peri-implant fractures. Conclusion: Distal interlocking screws are mainly used to prevent rotation. For stable fractures with intact lateral walls, long cephalomedullary nails can be used without distal interlocking screws. For any type of intertrochanteric fractures, distal interlocking screws are required when using short cephalomedullary nails for fixation. Different interlocking modes, the number of interlocking screws, and the application prospects of absorbable interlocking screws may be future research directions.

Protective effect of synbiotic combination of Lactobacillus plantarum SC-5 and olive oil extract tyrosol in a murine model of ulcerative colitis.

BACKGROUND: Ulcerative colitisis (UC) classified as a form of inflammatory bowel diseases (IBD) characterized by chronic, nonspecific, and recurrent symptoms with a poor prognosis. Common clinical manifestations of UC include diarrhea, fecal bleeding, and abdominal pain. Even though anti-inflammatory drugs can help alleviate symptoms of IBD, their long-term use is limited due to potential side effects. Therefore, alternative approaches for the treatment and prevention of inflammation in UC are crucial. METHODS: This study investigated the synergistic mechanism of Lactobacillus plantarum SC-5 (SC-5) and tyrosol (TY) combination (TS) in murine colitis, specifically exploring their regulatory activity on the dextran sulfate sodium (DSS)-induced inflammatory pathways (NF-κB and MAPK) and key molecular targets (tight junction protein). The effectiveness of 1 week of treatment with SC-5, TY, or TS was evaluated in a DSS-induced colitis mice model by assessing colitis morbidity and colonic mucosal injury (n = 9). To validate these findings, fecal microbiota transplantation (FMT) was performed by inoculating DSS-treated mice with the microbiota of TS-administered mice (n = 9). RESULTS: The results demonstrated that all three treatments effectively reduced colitis morbidity and protected against DSS-induced UC. The combination treatment, TS, exhibited inhibitory effects on the DSS-induced activation of mitogen-activated protein kinase (MAPK) and negatively regulated NF-κB. Furthermore, TS maintained the integrity of the tight junction (TJ) structure by regulating the expression of zona-occludin-1 (ZO-1), Occludin, and Claudin-3 (p < 0.05). Analysis of the intestinal microbiota revealed significant differences, including a decrease in Proteus and an increase in Lactobacillus, Bifidobacterium, and Akkermansia, which supported the protective effect of TS (p < 0.05). An increase in the number of Aspergillus bacteria can cause inflammation in the intestines and lead to the formation of ulcers. Bifidobacterium and Lactobacillus can regulate the micro-ecological balance of the intestinal tract, replenish normal physiological bacteria and inhibit harmful intestinal bacteria, which can alleviate the symptoms of UC. The relative abundance of Akkermansia has been shown to be negatively associated with IBD. The FMT group exhibited alleviated colitis, excellent anti-inflammatory effects, improved colonic barrier integrity, and enrichment of bacteria such as Akkermansia (p < 0.05). These results further supported the gut microbiota-dependent mechanism of TS in ameliorating colonic inflammation. CONCLUSION: In conclusion, the TS demonstrated a remission of colitis and amelioration of colonic inflammation in a gut microbiota-dependent manner. The findings suggest that TS could be a potential natural medicine for the protection of UC health. The above results suggest that TS can be used as a potential therapeutic agent for the clinical regulation of UC.

Readthrough events in plants reveal plasticity of stop codons.

Stop codon readthrough (SCR) has important biological implications but remains largely uncharacterized. Here, we identify 1,009 SCR events in plants using a proteogenomic strategy. Plant SCR candidates tend to have shorter transcript lengths and fewer exons and splice variants than non-SCR transcripts. Mass spectrometry evidence shows that stop codons involved in SCR events can be recoded as 20 standard amino acids, some of which are also supported by suppressor tRNA analysis. We also observe multiple functional signals in 34 maize extended proteins and characterize the structural and subcellular localization changes in the extended protein of basic transcription factor 3. Furthermore, the SCR events exhibit non-conserved signature, and the extensions likely undergo protein-coding selection. Overall, our study not only characterizes that SCR events are commonly present in plants but also identifies the recoding plasticity of stop codons, which provides important insights into the flexibility of genetic decoding.

Tailoring the Electronic Metal-Support Interactions in Supported Silver Catalysts through Al modification for Efficient Ethylene Epoxidation.

Metal-modified catalysts have attracted extraordinary research attention in heterogeneous catalysis due to their enhanced geometric and electronic structures and outstanding catalytic performances. Silver (Ag) possesses necessary active sites for ethylene epoxidation, but the catalyst activity is usually sacrificed to obtain high selectivity towards ethylene oxide (EO). Herein, we report that using Al can help in tailoring the unoccupied 3d state of Ag on the MnO2 support through strong electronic metal-support interactions (EMSIs), overcoming the activity-selectivity trade-off for ethylene epoxidation and resulting in a very high ethylene conversion rate (~100 %) with 90 % selectivity for EO under mild conditions (170 °C and atmospheric pressure). Structural characterization and theoretical calculations revealed that the EMSIs obtained by the Al modification tailor the unoccupied 3d state of Ag, modulating the adsorption of ethylene (C2H4) and oxygen (O2) and facilitating EO desorption, resulting in high C2H4 conversion. Meanwhile, the increased number of positively charge Ag+ lowers the energy barrier for C2H4(ads) oxidation to produce oxametallacycle (OMC), inducing the unexpectedly high EO selectivity. Such an extraordinary electronic promotion provides new promising pathways for designing advanced metal catalysts with high activity and selectivity in selective oxidation reactions.

[Long-term auditory monitoring in children with Alport syndrome based on different degrees of renal injury].

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.

Rhamnose-PEG-induced supramolecular helices: Addressing challenges of drug solubility and release efficiency in transdermal patch.

Transdermal drug delivery systems (TDDS) demand both high drug loading capacity and efficient delivery. In order to improve both simultaneously, this study aims to develop a novel rhamnose-induced pressure-sensitive adhesive (HPR) by dispersing the drug in the supramolecular helical structure. Ten model drugs, categorized as acidic and basic compounds, were chosen to understand the characteristics of the HPR and its inner mechanism. Notably, it enhanced drug loading by 1.41 to 5 times over commercially available pressure-sensitive adhesives Duro-Tak@ 87-4098 and Duro-Tak@ 87-2287, in addition to increasing drug release efficiency by a factor of about 5. Pharmacokinetic evaluation demonstrated that the HPR group had >4-fold (Tulobuterol TUL) and 3-fold (Diclofenac DIC) more area under the blood drug concentration curve (AUC) than the commercial TUL and DIC patches in the absence of added excipients and a significantly prolonged mean residence time (MRT) of >4-fold (TUL) and 3-fold (DIC), demonstrating the potential for highly efficacious and prolonged dosing. Furthermore, its safety and mechanical properties meet the requisite standards. Mechanistic inquiries unveiled that both acidic and basic drugs establish hydrogen bonds with HPR and become encapsulated within supramolecular helical structures. The supramolecular helical structures, significantly elevated both the enthalpy of the drug-HPR and entropy of the drugs release, thereby substantially enhancing drug delivery efficiency. In summary, HPR enabled a significant simultaneous enhancement of drug loading and drug delivery, which, together with its unique spatial structure, would contribute to the development of TDDS. In addition, the establishment of rhamnose-induced supramolecular helical structures would provide innovative pathways for different drug delivery systems.

A Triangular-Matrix-Based Spectral Encoding Method for Broadband Filtering and Reconstruction-Based Spectral Measurement.

Broadband filtering and reconstruction-based spectral measurement represent a hot technical route for miniaturized spectral measurement; the measurement encoding scheme has a great effect on the spectral reconstruction fidelity. The existing spectral encoding schemes are usually complex and hard to implement; thus, the applications are severely limited. Considering this, here, a simple spectral encoding method based on a triangular matrix is designed. The condition number of the proposed spectral encoding system is estimated and demonstrated to be relatively low theoretically; then, verification experiments are carried out, and the results show that the proposed encoding can work well under precise or unprecise encoding and measurement conditions; therefore, the proposed scheme is demonstrated to be an effective trade-off of the spectral encoding efficiency and implementation cost.

Establishment of a targeted analysis method for gangliosides in mouse tissues by HILIC-ESI-MS/MS.

Gangliosides play an imperative role in cell signaling, neuronal recovery, apoptosis, and other physiological processes. For example, GM3 can regulate hypothalamic leptin resistance and control energy homeostasis, GD3 can mediate cell proliferation and differentiation and induce apoptosis, and GQ1b can stimulate neurogenesis. Therefore, the present study sought to establish and optimize the targeted analysis method for ganglioside subclasses and their molecular species using hydrophilic interaction liquid chromatography-triple quadrupole-MS/MS (HILIC-QQQ-MS/MS). Additionally, the fragmentation pattern of different ganglioside subclasses and their retention time patterns were analyzed, providing more accurate qualitative results. The limit of quantitation (LOQ) was as low as 10-4 ng. Moreover, the molecular species of gangliosides in the liver, cortex, and hypothalamus of C57BL/6 mice were analyzed using the established method. A total of 23 ganglioside subclasses with 164 molecular species, including 40 O-acetylated ganglioside molecular species and 28 NeuGc ganglioside molecular species, were identified using the semi-quantitative analysis method of an external standard curve corrected by an internal standard. In addition to NeuGc gangliosides, the contents of ganglioside subclasses were more abundant in the mouse brain than those in the mouse liver; especially, the contents of unsaturated gangliosides in the hypothalamus were much higher than those in the liver. Among them, O-acetylated gangliosides were detected only in the cortex and hypothalamus at a concentration of up to 100 µg/mg protein (40 molecular species). Overall, the proposed method expanded the detectable number of ganglioside subclasses and molecular species in biological samples and provided more opportunities for further study of the biological functions of gangliosides.

A Rhamnose-PEG-Modified Dendritic Polymer for Long-Term Efficient Transdermal Drug Delivery.

This study introduces a dendronized pressure-sensitive adhesive, TMPE@Rha, addressing Food and Drug Administration (FDA) concerns about traditional pressure-sensitive adhesives (PSAs) in transdermal drug delivery systems. The unique formulation, composed of rhamnose, trihydroxypropane, and poly(ethylene glycol), significantly enhances cohesion and tissue adhesion. Leveraging rhamnose improves intermolecular interactions and surface chain mobility, boosting tissue adhesion. Compared to acrylic pressure-sensitive adhesive 87-DT-4098, TMPE@Rha shows substantial advantages, with up to 5 to 6 times higher peel strength on porcine and wood substrates. Importantly, it maintains strong human skin adhesion beyond 7 days without the typical "dark ring" phenomenon. When loaded with diclofenac, the adhesive exhibits 3.12 times greater peeling strength than commercial alternatives, sustaining human adhesion for up to 6 days. Rigorous analyses confirm rhamnose's role in increasing interaction strength. In vitro studies and microscopy demonstrate the polymer's ability to enhance drug loading and distribution on the skin, improving permeability. Biocompatibility tests affirm TMPE@Rha as nonirritating. In summary, TMPE@Rha establishes a new standard for PSAs in transdermal drug delivery systems, offering exceptional adhesion, robustness, and biocompatibility. This pioneering work provides a blueprint for next-generation, highly adhesive, drug-loaded PSAs that meet and exceed FDA criteria.

MAGL protects against renal fibrosis through inhibiting tubular cell lipotoxicity.

Rationale: Renal fibrosis, with no therapeutic approaches, is a common pathological feature in various chronic kidney diseases (CKD). Tubular cell injury plays a pivotal role in renal fibrosis. Commonly, injured tubular cells exhibit significant lipid accumulation. However, the underlying mechanisms remain poorly understood. Methods: 2-arachidonoylglycerol (2-AG) levels in CKD patients and CKD model specimens were measured using mass spectrometry. 2-AG-loaded nanoparticles were infused into unilateral ureteral obstruction (UUO) mice. Lipid accumulation and renal fibrosis were tested. Furthermore, monoacylglycerol lipase (MAGL), the hydrolyzing enzyme of 2-AG, was assessed in CKD patients and models. Tubular cell-specific MAGL knock-in mice were generated. Moreover, MAGL recombination protein was also administered to unilateral ischemia reperfusion injury (UIRI) mice. Besides, a series of methods including RNA sequencing, metabolomics, primary cell culture, lipid staining, etc. were used. Results: 2-AG was increased in the serum or kidneys from CKD patients and models. Supplement of 2-AG further induced lipid accumulation and fibrogenesis through cannabinoid receptor type 2 (CB2)/ß-catenin signaling. ß-catenin knockout blocked 2-AG/CB2-induced fatty acid ß-oxidation (FAO) deficiency and lipid accumulation. Remarkably, MAGL significantly decreased in CKD, aligning with lipid accumulation and fibrosis. Specific transgene of MAGL in tubular cells significantly preserved FAO, inhibited lipid-mediated toxicity in tubular cells, and finally retarded fibrogenesis. Additionally, supplementation of MAGL in UIRI mice also preserved FAO function, inhibited lipid accumulation, and protected against renal fibrosis. Conclusion: MAGL is a potential diagnostic marker for kidney function decline, and also serves as a new therapeutic target for renal fibrosis through ameliorating lipotoxicity.

Autologous follicular unit extraction transplant for postburn cicatricial alopecia: A single-center's retrospective case series.

BACKGROUND AND RATIONALE: Cicatricial alopecia not only affects patients' appearance but also has negative effects on their physical and mental well-being, as well as their daily lives. Therefore, it is essential to provide proactive treatment to patients. OBJECTIVE: To explore the clinical effects of autologous follicular unit extraction (FUE) transplantation in the treatment of secondary scarring alopecia caused by burn, and to evaluate its effectiveness. METHODS: A retrospective observational study has been conducted, which included 41 patients with secondary scarring alopecia caused by burn. All patients underwent initial autologous FUE hair transplantation surgery, and the occurrence of postoperative complications was monitored. Patient satisfaction was evaluated after 12 months post-surgery. RESULTS: Satisfaction assessments were conducted for all 41 patients. Out of the total, 31 individuals expressed being very satisfied, 7 individuals reported being satisfied, and 3 individuals indicated being not very satisfied. Among the patients, 3 experienced complications, including herpes in the donor area for one patient, temporary hair loss for another patient, and thick scab for the third patient. CONCLUSION: FUE hair transplantation yields positive results for secondary scarring alopecia caused by burn. It offers natural hair growth patterns, minimal trauma, quick recovery, high patient satisfaction, and few complications.

Synovial mesenchymal stem cell-derived exosomal miR-485-3p relieves cartilage damage in osteoarthritis by targeting the NRP1-mediated PI3K/Akt pathway: Exosomal miR-485-3p relieves cartilage damage.

Osteoarthritis (OA) is an age-related musculoskeletal disease that results in pain and functional disability. Stem cell therapy has been considered as a promising treatment for OA. In this study, the therapeutic action and potential mechanism of synovial mesenchymal stem cells (SMSCs)-derived exosomes (Exos) in OA cartilage damage were investigated. Cartilage cells were stimulated with IL-1ß to establish an in vitro model of OA cartilage damage. Cartilage cell functions were detected by CCK-8, scratch assay, and flow cytometry, respectively. Inflammatory cytokine levels were assessed by ELISA. Target molecule levels were measured by qRT‒PCR and Western blotting. Exos-induced differential expression of miRNAs in cartilage cells were analyzed by microarray analysis. The interaction between miR-485-3p and neuropilin-1 (NRP1) was validated by dual luciferase reporter and RIP assays. We found that treatment with Exos promoted proliferation, migration, and ECM secretion, but restrained apoptosis and inflammation of IL-1ß-exposed cartilage cells via up-regulation of miR-485-3p. Additionally, miR-485-3p directly targeted NRP1 to repress NRP1 expression, which subsequently caused inactivation of the PI3K/Akt pathway. The protective effect of Exos on cartilage damage was counteracted by NRP1 overexpression-mediated activation of the PI3K/Akt pathway. In conclusion, Exos delivered miR-485-3p to attenuate IL-1ß-induced cartilage degradation by targeting NRP1 and succedent inactivation of the PI3K/Akt pathway. Our findings shed light on the novel protective mechanism of Exos in OA, which suggest that the restoration of miR-485-3p by Exos might be a novel approach for OA treatment.

C-X-C chemokine receptor type 4 promotes tubular cell senescence and renal fibrosis through ß-catenin-inhibited fatty acid oxidation.

The prevalence of chronic kidney disease (CKD) is highly increasing. Renal fibrosis is a common pathological feature in various CKD. Previous studies showed tubular cell senescence is highly involved in the pathogenesis of renal fibrosis. However, the inducers of tubular senescence and the underlying mechanisms have not been fully investigated. C-X-C motif chemokine receptor 4 (CXCR4), a G-protein-coupled seven-span transmembrane receptor, increases renal fibrosis and plays an important role in tubular cell injury. Whereas, whether CXCR4 could induce tubular cell senescence and the detailed mechanisms have not studied yet. In this study, we adopted adriamycin nephropathy and 5/6 nephrectomy models, and cultured tubular cell line. Overexpression or knockdown of CXCR4 was obtained by injection of related plasmids. We identified CXCR4 increased in injury tubular cells. CXCR4 was expressed predominantly in renal tubular epithelial cells and co-localized with adipose differentiation-related protein (ADRP) as well as the senescence-related protein P16INK4A . Furthermore, we found overexpression of CXCR4 greatly induced the activation of ß-catenin, while knockdown of CXCR4 inhibited it. We also found that CXCR4 inhibited fatty acid oxidation and triggered lipid deposition in tubular cells. To inhibit ß-catenin by ICG-001, an inhibitor of ß-catenin, could significantly block CXCR4-suppressed fatty acid oxidation. Taken together, our results indicate that CXCR4 is a key mediator in tubular cell senescence and renal fibrosis. CXCR4 promotes tubular cell senescence and renal fibrosis by inducing ß-catenin and inhibiting fatty acid metabolism. Our findings provide a new theory for tubular cell injury in renal fibrosis.