Efficacy and safety of phototherapies for upper lip scars in cleft lip patients: A systematic review and meta-analysis.

OBJECTIVE: Cleft lip is a prevalent congenital developmental defect, and its surgical repair often results in scarring that adversely impacts facial aesthetics, function, and mental health. Numerous studies have examined the efficacy and safety of phototherapy for scar treatment. However, definitive evidence is lacking. This study aims to evaluate the effectiveness and safety of phototherapies for treating upper lip scars in cleft lip patients. METHODS: We searched PubMed, Cochrane Library, Embase, and Web of Science databases using specific search terms. We collected clinical trials on laser or other phototherapy treatments for upper lip scars after cleft lip surgery published up to the end of March 2024. Two researchers independently screened the literature, extracted data, and assessed quality based on inclusion and exclusion criteria. The data were analyzed by using RevMan 5.4 statistical software. RESULTS: A total of 9 studies were included. ① Analysis of the clinical efficacy rate between the control group (routine care) and the intervention group (phototherapy) showed that laser or intense pulsed light (IPL) treatment significantly reduced total VSS scores (P<0.0001). ② Analysis of the Pretest-Posttest cohort showed that total VSS scores were significantly reduced after phototherapy (P<0.00001). ③ Timing of phototherapy intervention analysis: early postoperative phototherapy intervention had a better effect. None of the literature reported permanent complications, nor were there any serious adverse events, only localized temporary erythema or blisters. CONCLUSION: Phototherapy can effectively improve the total VSS scores of upper lip scars after cleft lip surgery (including skin color, vascular distribution, softness, and thickness) with no apparent adverse reactions or serious complications. Early phototherapy intervention for upper lip scars has a better effect.

Mining and multifaceted applications of phage lysin for combatting Vibrio parahaemolyticus.

Vibrio parahaemolyticus, a prevalent foodborne pathogen found in both water and seafood, poses substantial risks to public health. The conventional countermeasure, antibiotics, has exacerbated the issue of antibiotic resistance, increasing the difficulty of controlling this bacterium. Phage lysins, as naturally occurring active proteins, offer a safe and reliable strategy to mitigate the impact of V. parahaemolyticus on public health. However, there is currently a research gap concerning bacteriophage lysins specific to Vibrio species. To address this, our study innovatively and systematically evaluates 37 phage lysins sourced from the NCBI database, revealing a diverse array of conserved domains and notable variations in similarity among Vibrio phage lysins. Three lysins, including Lyz_V_pgrp, Lyz_V_prgp60, and Lyz_V_zlis, were successfully expressed and purified. Optimal enzymatic activity was observed at 45℃, 800 mM NaCl, and pH 8-10, with significant enhancements noted in the presence of 1 mM membrane permeabilizers such as EDTA or organic acids. These lysins demonstrated effective inhibition against 63 V. parahaemolyticus isolates from clinical, food, and environmental sources, including the reversal of partial resistance, synergistic interactions with antibiotics, and disruption of biofilms. Flow cytometry analyses revealed that the combination of Lyz_V_pgp60 and gentamicin markedly increased bacterial killing rates. Notably, Lyz_V_pgrp, Lyz_V_pgp60, and Lyz_V_zlis exhibited highly efficient biofilm hydrolysis, clearing over 90 % of preformed V. parahaemolyticus biofilms within 48 h. Moreover, these lysins significantly reduced bacterial loads in various food samples and environmental sources, with reductions averaging between 1.06 and 1.29 Log CFU/cm2 on surfaces such as stainless-steel and bamboo cutting boards and approximately 0.87 CFU/mL in lake water and sediment samples. These findings underscore the exceptional efficacy and versatile application potential of phage lysins, offering a promising avenue for controlling V. parahaemolyticus contamination in both food and environmental contexts.

Abnormal late postprandial glucagon response in type 1 diabetes is a function of differences in stimulated C-peptide concentrations.

Background: The functional changes in alpha cells in patients with type 1 diabetes (T1D) with different residual beta cell functions remain poorly elucidated. The study aimed to investigate the relationship between glucagon secretion and C-peptide levels and to explore the relationship between glucagon response and glucose increment in respond to a secretagogue in a steamed bread meal tolerance test (BMTT) in T1D. Methods: The study enrolled 43 adult patients with T1D and 24 healthy control subjects. Patients with T1D who underwent BMTT were divided into two groups based on peak C-peptide levels: C peptide low (CPL; C-peptide < 200 pmol/L; n=14) and high (CPH; C peptide ≥ 200 pmol/L; n=29). Plasma glucose, C-peptide, glucagon levels at 0, 30, 60, 120, and 180 min were measured. The glucagon response to the BMTT was defined by areas under the curve (AUC) as early (AUC0-30), late (AUC30-180), or total (AUC0-180) glucagon. Results: Compared to healthy individuals, fasting plasma glucagon was lower and postprandial plasma glucagon level was increased in patients with T1D. Glucagon levels after BMTT between the CPL and CPH group showed significant group by time interaction. Peak glucagon and glucagon at 60-180 min, total and late glucagon response were higher in CPL than CPH group, while fasting glucagon and early glucagon response adjusted for glucose were comparable between CPL and CPH group. The higher late glucagon response and late glucagon response adjusted for glucose were associated with lower peak C-peptide in T1D. The higher late glucagon response and lower peak C-peptide were associated with the higher value of ▵glucose at 180 min. Conclusion: Stimulated C-peptide levels affect the paradoxical increase in postprandial glucagon secretion in patients with T1D, especially late glucagon response. The exaggerated postprandial glucagon secretion further stimulates the elevation of postprandial glucose in patients with T1D.

PDMS-Based Hierarchical Superhydrophobic Fabric Coating Fabricated by Thermal Treatment and Electrostatic Flocking Technology.

Superhydrophobic coatings have broad applications in a variety of industries. By using a low-surface-energy material and creating nanoscale roughness, a superhydrophobic surface can be produced. To overcome the health and environmental concerns of fluorine-based materials and the limitations of large-scale rough microstructure fabrication, a poly(dimethylsiloxane) (PDMS)-based hierarchical superhydrophobic fabric coating prepared by simple thermal treatment and electrostatic flocking technology was introduced in this study. High-temperature thermal treatment is employed to create PDMS nanoparticle-decorated carbon fibers, which are further vertically implanted onto the surface of cotton fabric via electrostatic flocking technology. The environmentally friendly PDMS nanoparticles were adopted as low-surface-energy materials, and the electrostatic flocking technology was utilized to generate a vertically aligned carbon fiber array coating, mimicking a lotus leaf-like superhydrophobic surface microstructure. Therefore, an ultrahigh water contact angle of 173.9 ± 2.8° and a low sliding angle of 1 ± 0.5° can be obtained by the fabric coating with a PDMS-to-carbon fiber ratio of 20:1. The prepared superhydrophobic fabric also exhibits an excellent self-cleaning property and great durability after 60 cycles of washing. Through commercially available thermal treatment and electrostatic flocking processes, this strategy for fabricating fluorine-free superhydrophobic fabric can be easily scaled up for commercial manufacturing and promotes the design of superhydrophobic coatings for other substrates.

Early comprehensive pulmonary rehabilitation for hospitalized patients with acute ex-acerbation of chronic obstructive pulmonary disease: a randomized controlled trial.

OBJECTIVE: To investigate whether an early comprehensive pulmonary rehabilitation intervention initiated during hospital admission is safe and effective for patients with acute exacerbation of chronic obstructive pulmonary disease. DESIGN: Prospective randomized controlled study. SUBJECTS/PATIENTS: Patients with acute exacerbation of chronic obstructive pulmonary disease. METHODS: In total, 108 patients were randomized to the early comprehensive pulmonary rehabilitation and usual care groups within 48 hours. The 6-min walking distance, quality of life, breathlessness, and inspiratory muscle strength were measured on admission and discharge. Any adverse events of pulmonary rehabilitation were recorded. RESULTS: On discharge, the patients in the early comprehensive pulmonary rehabilitation group had a more significant improvement in the 6-min walking distance (47.5 vs 23.0, p = 0.04). There was no significant difference in quality of life and breathlessness between the 2 groups. In the early comprehensive pulmonary rehabilitation group, inspiratory muscle strength and peak inspiratory flow were significantly improved, and the changes were much more pronounced than in the usual care group. There were no adverse events. CONCLUSION: Early comprehensive pulmonary rehabilitation is safe and effective for hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease, and should be performed during the early stage of hospitalization.

Lathyrane diterpenoids with multidrug resistance reversal activity from the tubers of Euphorbia antiquorum.

Nine previously unreported lathyrane diterpenoids named euphorantesters A-I, along with 16 known analogues, have been separated from the tubers of Euphorbia antiquorum. Their structures were established by means of spectroscopic analyses, time-dependent density functional theory based electronic circular dichroism calculation and single crystal X-ray crystallography. Their reversal ability against P-glycoprotein-mediated multidrug resistance (MDR) in MCF-7/ADR cell line was then evaluated, and 15 ones exhibited moderate MDR reversal activity with reversal fold falling in the range of 1.12-13.15. The most active euphorantester B could effectively increase the sensitivity of MCF-7/ADR cell to adriamycin comparably to the reference drug verapamil.

Synergistic effects of sulfur vacancies and internal electric fields in FeS/MoS2 heterojunctions: A new approach to photocatalytic chromium removal.

Molybdenum disulfide (MoS2) is heralded as an exemplary two-dimensional (2D) functional material, largely attributed to its distinctive layered structure. Upon forming heterojunctions with reducing species, MoS2 displays remarkable photocatalytic properties. In this research, we fabricated a novel heterojunction photocatalyst, FeS/MoS2-0.05, through the integration of FeS with hollow MoS2. This composite aims at the efficient photocatalytic reduction of hexavalent chromium (Cr(VI)). A comprehensive array of characterization techniques unveiled that MoS2 flakes, dispersed on FeS, provide numerous active sites for photocatalysis at the heterojunction interface. The inclusion of FeS seemingly promotes the formation of sulfur vacancies on MoS2. Consequently, this heterojunction catalyst exhibits photocatalytic activity surpassing pristine MoS2 by a factor of 3.77. The augmented activity of the FeS/MoS2-0.05 catalyst is attributed chiefly to an internal electric field at the interface. This field enhances the facilitation of charge transfer and separation significantly. Density functional theory (DFT) calculations, coupled with experimental analyses, corroborate this observation. Additionally, DFT calculations indicate that sulfur vacancies act as pivotal sites for Cr(VI) adsorption. Significantly, the adsorption energy of Cr(VI) species shows enhanced favorability under acidic conditions. Our results suggest that the FeS/MoS2-0.05 heterojunction photocatalyst presents substantial potential for the remediation of Cr(VI)-contaminated wastewater.

Beta-blocker drives the conjugative transfer of multidrug resistance genes in pure and complex biological systems.

Drug resistance poses a high risk to human health. Extensive use of non-antibiotic drugs contributes to antibiotic resistance genes (ARGs) transfer. However, how they affect the spread of broad-host plasmids in complex biological systems remains unknown. This study investigated the effect of metoprolol on the transfer frequency and host range of ARGs in both intrageneric and intergeneric pure culture systems, as well as in anammox microbiome. The results showed that environmental concentrations of metoprolol significantly promoted the intrageneric and intergeneric conjugative transfer. Initially, metoprolol induced excessive oxidative stress, resulting in high cell membrane permeability and bacterial SOS response. Meanwhile, more pili formation increased the adhesion and contact between bacteria, and the abundance of conjugation-related genes also increased significantly. Activation of the electron transport chain provided more ATP for this energy-consuming process. The underlying mechanism was further verified in the complex anammox conjugative system. Metoprolol induced the enrichment of ARGs and mobile genetic elements. The enhanced bacterial interaction and energy generation facilitated the high conjugative transfer frequency of ARGs. In addition, plasmid-borne ARGs tended to transfer to opportunistic pathogens. This work raises public concerns about the health and ecological risks of non-antibiotic drugs.

Super-Selective Intra-arterial Thrombolytic Therapy for Peripheral Facial Paralysis After Postauricular Hyaluronic Acid Injection for the Esthetic Correction of Lying Ears.

BACKGROUND: Hyaluronic acid (HA) injection in the auricular base is one of the most popular and non-surgical cosmetic procedures for correcting lying ears and optimizing the facial profile because of its minimal invasiveness, immediate effect and safety (Li et al. in Aesthet Surg J 44: 746-75, 2024). But we have recently discovered that this treatment may lead to a new and rare complication called peripheral facial paralysis that has never been reported before. Until now, the etiology, clinical traits, treatment strategies, outcomes and possible reversibility have not been characterized. METHODS: In the present study, we enrolled 4 patients with peripheral facial paralysis after subcutaneous postauricular HA filler injection. Preoperative digital subtraction angiography revealed a vascular embolism. Then, the patients underwent super-selective facial arterial thrombolytic therapy via hyaluronidase and papaverine injections. Simultaneously, general symptomatic treatment and nutritional therapy were performed. RESULTS: The patients were relieved of their clinical symptoms and the significant improvement was observed in terms of motor function in her left facial areas after treatment. The auricular skin necrosis of all patients was restored to near normal appearance. CONCLUSION: Our results indicate that super-selective facial arterial thrombolytic therapy is feasible for patients with peripheral facial paralysis induced by HA embolism. It was also beneficial in the recovery from skin necrosis. The therapy was shown to be worthy of clinical application. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Investigation of the relationship between COVID-19 and pancreatic cancer using bioinformatics and systems biology approaches.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, poses a huge threat to human health. Pancreatic cancer (PC) is a malignant tumor with high mortality. Research suggests that infection with SARS-CoV-2 may increase disease severity and risk of death in patients with pancreatic cancer, while pancreatic cancer may also increase the likelihood of contracting SARS-CoV-2, but the link is unclear. METHODS: This study investigated the transcriptional profiles of COVID-19 and PC patients, along with their respective healthy controls, using bioinformatics and systems biology approaches to uncover the molecular mechanisms linking the 2 diseases. Specifically, gene expression data for COVID-19 and PC patients were obtained from the Gene Expression Omnibus datasets, and common differentially expressed genes (DEGs) were identified. Gene ontology and pathway enrichment analyses were performed on the common DEGs to elucidate the regulatory relationships between the diseases. Additionally, hub genes were identified by constructing a protein-protein interaction network from the shared DEGs. Using these hub genes, we conducted regulatory network analyses of microRNA/transcription factors-genes relationships, and predicted potential drugs for treating COVID-19 and PC. RESULTS: A total of 1722 and 2979 DEGs were identified from the transcriptome data of PC (GSE119794) and COVID-19 (GSE196822), respectively. Among these, 236 common DEGs were found between COVID-19 and PC based on protein-protein interaction analysis. Functional enrichment analysis indicated that these shared DEGs were involved in pathways related to viral genome replication and tumorigenesis. Additionally, 10 hub genes, including extra spindle pole bodies like 1, holliday junction recognition protein, marker of proliferation Ki-67, kinesin family member 4A, cyclin-dependent kinase 1, topoisomerase II alpha, cyclin B2, ubiquitin-conjugating enzyme E2 C, aurora kinase B, and targeting protein for Xklp2, were identified. Regulatory network analysis revealed 42 transcription factors and 23 microRNAs as transcriptional regulatory signals. Importantly, lucanthone, etoposide, troglitazone, resveratrol, calcitriol, ciclopirox, dasatinib, enterolactone, methotrexate, and irinotecan emerged as potential therapeutic agents against both COVID-19 and PC. CONCLUSION: This study unveils potential shared pathogenic mechanisms between PC and COVID-19, offering novel insights for future research and therapeutic strategies for the treatment of PC and SARS-CoV-2 infection.

Determination of Antioxidant, Cytotoxicity, and Anti-human Lung Cancer Properties of Silver Nanoparticles Green-Formulated by Foeniculum vulgare Extract Combined with Radiotherapy.

The current investigation involved the silver nanoparticles green synthesis utilizing the aqueous extract derived from the Foeniculum vulgare leaves (AgNPs@FV). The effectiveness of these newly developed nanoparticles in conjunction with radiotherapy was evaluated on lung cancer cells. The synthesized AgNPs@FV underwent characterization through various analytical techniques such as energy dispersive X-ray (EDX), field emission-scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), and ultraviolet-visible (UV-Vis) spectrophotometry. The efficacy of AgNPs@FV in conjunction with radiotherapy against human lung cancer was assessed through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The AgNPs@FV exhibited a spherical morphology ranging in size from 10.16 to 42.74 nm. The EDX diagram of nanoparticles shows energy signals at 3.02 and 2.64 keV, which are attributed to Ag Lß and Ag Lα, respectively. During the antioxidant evaluation, AgNPs@FV and butylated hydroxytoluene (BHT) displayed IC50 values of 166 and 59 µg/mL, respectively. The cells treated with AgNPs@FV in conjunction with radiotherapy were evaluated using the MTT assay over 48 h to determine cytotoxicity and anti-human lung cancer characteristics on normal (human umbilical vein endothelial cell (HUVEC)) and lung cancer cells and exhibited IC50 values of 211, 166, and 296 µg/mL against NCI-H2126, NCI-H1299, and NCI-H1437, respectively. Furthermore, the malignant lung cell viability decreased when treated with a combination of AgNPs@FV and radiotherapy. Based on the aforementioned findings, it is possible that the newly developed AgNPs@FV could serve as a novel chemotherapeutic medication or adjunct for addressing lung cancer following the completion of clinical trials involving human subjects.

Feasibility and Favorable Responses Following Investigational CAR T-Cell Therapy for Relapsed and Refractory Infant ALL.

Infants with B-cell acute lymphoblastic leukemia (B-ALL) continue to have significantly worse outcomes compared to older children with B-ALL, and those with relapsed or refractory (R/R) infant ALL have especially dismal outcomes with conventional treatment. CD19-targeting chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable success in the treatment of R/R childhood B-ALL, though the majority of reports have been in non-infant patients. Barriers to the successful implementation of CAR T-cell therapy in infant B-ALL include challenges related to apheresis, product manufacturing and disease-specific considerations such as lineage switch. We describe our experience utilizing two experimental CD19-CAR T-cell products, SCRI-CAR19 or SCRI-CAR19x22, for 19 patients with R/R infant B-ALL enrolled on three clinical trials. CAR T-cell products were successfully manufactured in 18/19 (94.7%) patients, with a median age of 22.5 months at enrollment (range, 14.5-40.1 months). Sixteen of 17 (94.1%) treated patients achieved a complete remission without detectable minimal residual disease. The 1-year leukemia free survival was 75% and 1-year overall survival was 76.5%, with a median follow up time of 35.8 months (range, 1.7-83.6 months). Cytokine release syndrome (CRS) occurred in 14/17 (82.4%) patients, with only 1 patient experiencing Grade 3 CRS. Neurotoxicity occurred in 2/17 (11.8%) patients with all events ≤ Grade 2. With the successful early clinical experience of CAR T-cell therapy in this population, more systematic evaluation specific to infant ALL is warranted.

Multiple Roles of Anions on the Degradation Efficiency and Mineralization Pathway of Recalcitrant Acetaldehyde by Vacuum Ultraviolet (185 nm) Oxidation.

Vacuum-UV (185 nm, VUV) is widely applied to polish reverse osmosis permeate (ROP), such as the production of electronics-grade ultrapure water. In this study, the VUV oxidation of acetaldehyde, a common carbonyl in ROP, was found to be influenced by anions even at low concentrations. Interestingly, the influencing extent and mechanism varied depending on the anions. Bicarbonate minimally affected the VUV-photon absorption and •OH consumption, but at 5000 µg-C·L-1, it decreased the degradation of acetaldehyde by 58.7% possibly by scavenging organic radicals or other radical chain reactions. Nitrate strongly competed for VUV-photon absorption and •OH scavenging through the formation of nitrite, and at 500 µg-N·L-1, it decreased the removal rate of acetaldehyde degradation by 71.2% and the mineralization rate of dissolved organic carbon by 53.4%. Chloride competed for VUV-photon absorption and also generated reactive chlorine species, which did not affect acetaldehyde degradation but influenced the formation of organic byproducts. The radical chain reactions or activation of anions under VUV irradiation could compensate for the decrease in oxidation performance and need further investigation. In real ROPs, the VUV oxidation of acetaldehyde remained efficient, but mineralization was hindered due to nitrate and chloride anions. This study deepens the understanding of the photochemistry and feasibility of VUV in water with low concentrations of anions.

Th1/Th2 Imbalance in Peripheral Blood Echoes Microglia State Dynamics in CNS During TLE Progression.

Central and systemic inflammation play pivotal roles in epileptogenesis and proepileptogenesis in temporal lobe epilepsy (TLE). The interplay between peripheral CD4+ T cells and central microglia orchestrates the "systemic-central" immune response in TLE. However, the precise molecular mechanisms linking central and systemic inflammation in TLE remain unknown. This preliminary findings revealed an imbalance in Th1/Th2 subsets in the periphery，accompanied by related cytokines release in TLE patients. they proposed that this peripheral Th1/Th2 imbalance may influence central inflammation by mediating microglial state dynamics within epileptic foci and distant brain regions. In Li-pilocarpine-induced TLE rats, a peripheral Th1/Th2 imbalance and observed corresponding central and systemic responses is confirmed. Notably, CD4+ T cells infiltrated through the compromised blood-brain barrierand are spatially close to microglia around epileptic foci. Intravenous depletion and reinfusion of CD4+ T cells modulated microglia state dynamics and altered neuroinflammatory cytokines secretion. Moreover, mRNA sequencing of the human hippocampus identified Notch1 as a key regulator of Th1/Th2 differentiation, CD4+ T cell recruitment to brain infiltration sites, and the regulation of microglial responses, seizure frequency, and cognition. This study underscores the significance of Th1/Th2 imbalance in modulating the "systemic-central" response in TLE, highlighting Notch1 as a potential therapeutic target.

Epigenetics of Skeletal Muscle Atrophy.

Skeletal muscle atrophy, characterized by diminished muscle strength and mass, arises from various causes, including malnutrition, aging, nerve damage, and disease-related secondary atrophy. Aging markedly escalates the prevalence of sarcopenia. Concurrently, the incidence of muscle atrophy significantly rises among patients with chronic ailments such as heart failure, diabetes, and chronic obstructive pulmonary disease (COPD). Epigenetics plays a pivotal role in skeletal muscle atrophy. Aging elevates methylation levels in the promoter regions of specific genes within muscle tissues. This aberrant methylation is similarly observed in conditions like diabetes, neurological disorders, and cardiovascular diseases. This study aims to explore the relationship between epigenetics and skeletal muscle atrophy, thereby enhancing the understanding of its pathogenesis and uncovering novel therapeutic strategies.

Lignin nanoparticles formation by multiscale structure control to regulate morphology and their adsorption, nucleation, and growth on chitin nanofibers.

The lignin nanoparticles (LNPs) synthesis relies on lignin polymers with heterogeneous molecules and properties, which impose significant limitations on the preparation and property regulation. The multiscale structure of lignin from monomers to oligomers, provides a potential pathway for precise regulation of its physical and chemical properties. The study addresses this challenge by employing coniferyl alcohol and sinapyl alcohol as monomers and separately utilizing the Zulaufverfaren (ZL) and Zutropfverfaren (ZT) methods to synthesize different types of lignin dehydrogenation polymers (DHPs) including guaiacyl (G)-ZL-DHP, G-ZT-DHP, syringyl (S)-ZL-DHP, and S-ZT-DHP. The investigation highlights the chemical bonds as essential components of lignin primary structure. Additionally, the secondary structure is influenced by branched and linear molecular structures. G unit provides some branching points, which are utilized and amplified in the ZL process of DHPs synthesis. The branched DHPs aggregate at the edge and form rod-like LNPs. While linear DHPs aggregate around the center, presenting polygonal LNPs. The study identifies that the branched LNPs, characterized by more surface charges and lower steric hindrance, can form a stable complex with chitin nanofibers. Emulsions with varying oil-to-water ratios were subsequently prepared, opening a new window for the application of LNPs in fields such as food and cosmetics.

Tumor Cell-Derived Exosomal Hybrid Nanosystems Loaded with Rhubarbic Acid and Tanshinone IIA for Sepsis Treatment.

Background: Sepsis continues to exert a significant impact on morbidity and mortality in clinical settings, with immunosuppression, multi-organ failure, and disruptions in gut microbiota being key features. Although rheinic acid and tanshinone IIA show promise in mitigating macrophage apoptosis in sepsis treatment, their precise targeting of macrophages remains limited. Additionally, the evaluation of intestinal flora changes following treatment, which plays a significant role in subsequent cytokine storms, has been overlooked. Leveraging the innate inflammation chemotaxis of tumor cell-derived exosomes allows for their rapid recognition and uptake by activated macrophages, facilitating phenotypic changes and harnessing anti-inflammatory effects. Methods: We extracted exosomes from H1299 cells using a precipitation method. Then we developed a tumor cell-derived exosomal hybrid nanosystem loaded with rhubarbic acid and tanshinone IIA (R+T/Lipo/EXO) for sepsis treatment. In vitro studies, we verify the anti-inflammatory effect and the mechanism of inhibiting cell apoptosis of nano drug delivery system. The anti-inflammatory effects, safety, and modulation of intestinal microbiota by the nanoformulations were further validated in the in vivo study. Results: Nanoformulation demonstrated enhanced macrophage internalization, reduced TNF-α expression, inhibited apoptosis, modulated intestinal flora, and alleviated immunosuppression. Conclusion: R+T/Lipo/EXO presents a promising approach using exosomal hybrid nanosystems for treating sepsis.

Protein-extending ACTN2 frameshift variants cause variable myopathy phenotypes by protein aggregation.

OBJECTIVE: The objective of the study is to characterize the pathomechanisms underlying actininopathies. Distal myopathies are a group of rare, inherited muscular disorders characterized by progressive loss of muscle fibers that begin in the distal parts of arms and legs. Recently, variants in a new disease gene, ACTN2, have been shown to cause distal myopathy. ACTN2, a gene previously only associated with cardiomyopathies, encodes alpha-actinin-2, a protein expressed in both cardiac and skeletal sarcomeres. The primary function of alpha-actinin-2 is to link actin and titin to the sarcomere Z-disk. New ACTN2 variants are continuously discovered; however, the clinical significance of many variants remains unknown. Thus, lack of clear genotype-phenotype correlations in ACTN2-related diseases, actininopathies, persists. METHODS: Functional characterization in C2C12 cell model of several ACTN2 variants is conducted, including frameshift and missense variants associated with dominant and recessive actininopathies. We assess the genotype-phenotype correlations of actininopathies using clinical data from several patients carrying these variants. RESULTS: The results show that the missense variants associated with a recessive form of actininopathy do not cause detectable alpha-actinin-2 aggregates in the cell model. Conversely, dominant frameshift variants causing a protein extension do form alpha-actinin-2 aggregates. INTERPRETATION: The results suggest that alpha-actinin-2 aggregation is the disease mechanism underlying some dominant actininopathies, and thus, we recommend that protein-extending frameshift variants in ACTN2 should be classified as pathogenic. However, this mechanism is likely elicited by only a limited number of variants. Alternative functional characterization methods should be explored to further investigate other molecular mechanisms underlying actininopathies.

A novel approach to treating post-stroke depression: administration of Botulinum Toxin A via local facial injection.

Background: Post-stroke depression (PSD) is a frequent complication following a stroke, characterized by prolonged feelings of sadness and loss of interest, which can significantly impede stroke rehabilitation, increase disability, and raise mortality rates. Traditional antidepressants often have significant side effects and poor patient adherence, necessitating the exploration of more suitable treatments for PSD. Previous researchers and our research team have discovered that Botulinum Toxin A (BoNT-A) exhibits antidepressant effects. Therefore, our objective was to assess the efficacy and side effects of BoNT-A treatment in patients with PSD. Methods: A total of 71 stroke patients meeting the inclusion criteria were allocated to the two group. 2 cases were excluded due to severe neurological dysfunction that prevented cooperation and 4 cases were lost follow-up. Ultimately, number of participants in the BoNT-A group (n = 32) and Sertraline group (n = 33). Treatment efficacy was evaluated 1, 2, 4, 8 and 12 weeks post-treatment. Results: There were no significant differences in baseline characteristics between the two groups (p > 0.05). Both groups exhibited comparable treatment efficacy, with fewer side effects observed in the BoNT-A group compared to the Sertraline group. BoNT-A therapy demonstrated significant effects as early as the first week (p < 0.05), and by the 12th week, there was a notable decrease in neuropsychological scores, significantly lower than the baseline level. The analysis revealed significant differences in measurements of the Hamilton Depression Scale (HAMD) (F(770) = 12.547, p = 0.000), Hamilton Anxiety Scale (HAMA) (F(951) = 10.422, p = 0.000), Self-Rating Depression Scale (SDS) (F(1385) = 10.607, p = 0.000), and Self-Rating Anxiety Scale (SAS) (F(1482) = 11.491, p = 0.000). Conclusion: BoNT-A treatment effectively reduces depression symptoms in patients with PSD on a continuous basis.

Nano-Se exhibits limited protective effect against heat stress induced poor breast muscle meat quality of broilers compared with other selenium sources.

BACKGROUND: At present, heat stress (HS) has become a key factor that impairs broiler breeding industry, which causes growth restriction and poor meat quality of broilers. Selenium (Se) is an excellent antioxidant and plays a unique role in meat quality improvement. Recent years, nano-selenium (NanoSe) has received tremendous attention in livestock production, due to its characteristic and good antibacterial performance in vitro. Here, we developed the heat stressed-broiler model to investigate the protective effects of NanoSe on growth performance and meat quality of broilers and compare whether there are differences with that of other Se sources (Sodium selenite, SS; Selenoyeast, SeY; Selenomethionine, SeMet). RESULTS: HS jeopardized the growth performance and caused poor meat quality of breast muscle in broilers, which were accompanied by lowered antioxidant capacity, increased glycolysis, increased anaerobic metabolism of pyruvate, mitochondrial stress and abnormal mitochondrial tricarboxylic acid (TCA) cycle. All Se sources supplementation exhibited protective effects, which increased the Se concentration and promoted the expression of selenoproteins, improved the mitochondrial homeostasis and the antioxidant capacity, and promoted the TCA cycle and the aerobic metabolism of pyruvate, thus improved the breast muscle meat quality of broilers exposed to HS. However, unlike the other three Se sources, the protective effect of NanoSe on meat quality of heat stressed-broilers was not ideal, which exhibited limited impact on the pH value, drip loss and cooking loss of the breast muscle. Compared with the other Se sources, broilers received NanoSe showed the lowest levels of slow MyHC, the highest levels of fast MyHC and glycogen, the highest mRNA levels of glycolysis-related genes (PFKM and PKM), the highest protein expression of HSP60 and CLPP, and the lowest enzyme activities of GSH-Px, citroyl synthetase (CS) and isocitrate dehydrogenase (ICD) in breast muscle. Consistent with the SS, the Se deposition in breast muscle of broilers received NanoSe was lower than that of broilers received SeY or SeMet. Besides, the regulatory efficiency of NanoSe on the expression of key selenoproteins (such as SELENOS) in breast muscle of heat stressed-broilers was also worse than that of other Se sources. CONCLUSION: Through comparing the meat quality, Se deposition, muscle fiber type conversion, glycolysis, mitochondrial homeostasis, and mitochondrial TCA cycle-related indicators of breast muscle in heat stressed broilers, we found that the protective effects of organic Se (SeY and SeMet) are better than that of inorganic Se (SS) and NanoSe. As a new Se source, though NanoSe showed some protective effect on breast muscle meat quality of heat stressed broilers, the protective effect of NanoSe is not ideal, compared with other Se sources.