The effectiveness and safety of centralized early rehabilitation care for critically ill children with severe acquired brain injury: A retrospective cohort and implementation study.

BACKGROUND: Most children with neurocritical illness are at risk of physical, neurocognitive, and psychosocial sequelae and need centralized early rehabilitation care. OBJECTIVE: To identify the effectiveness and safety of centralized early rehabilitation care for children with severe acquired brain injury. METHODS: This is a mixed methods study-an implementation study and single-center retrospective cohort study with historical control. All children with severe acquired brain injury hospitalized in a specialized rehabilitation center in a comprehensive tertiary pediatric hospital between September 2016 and August 2020 were included. Patients treated in the centralized early rehabilitation unit were compared to historical controls dispersed in the normal inpatient rehabilitation ward. The effectiveness outcomes were measured by the Pediatric Cerebral Performance Category (PCPC) scale and the incidence of newly onset comorbidities. The safety outcomes were indicated by the mortality rate and the incidence of unexpected referrals. RESULTS: One hundred seventy-five patients were included. The delta PCPC scores of the first 4 weeks of inpatient rehabilitation in the intervention group were significantly lower than the control group (Z = -2.395, p = 0.017). The PCPC scores at 1 year in the intervention group were significantly reduced as compared to the control group (Z = -3.337, p = 0.001). The incidence of newly onset pneumonia/bronchitis was also decreased in the intervention group (χ2 = 4.517, p = 0.034). No death of patients was recorded, and there was no significant difference in unexpected referral rate between the two groups (χ2 = 0.374, p = 0.541). CONCLUSIONS: The centralized pediatrics early rehabilitation unit is effective and safe for children with severe acquired brain injury. Further multicenter prospective implementation studies on effectiveness, safety, and economic evaluation are needed.

Molecular insights into linkages among free-floating macrophyte-derived organic matter, the fate of antibiotic residues, and antibiotic resistance genes.

Macrophyte rhizospheric dissolved organic matter (ROM) served as widespread abiotic components in aquatic ecosystems, and its effects on antibiotic residues and antibiotic resistance genes (ARGs) could not be ignored. However, specific influencing mechanisms for ROM on the fate of antibiotic residues and expression of ARGs still remained unclear. Herein, laboratory hydroponic experiments for water lettuce (Pistia stratiotes) were carried out to explore mutual interactions among ROM, sulfamethoxazole (SMX), bacterial community, and ARGs expression. Results showed ROM directly affect SMX concentrations through the binding process, while CO and N-H groups were main binding sites for ROM. Dynamic changes of ROM molecular composition diversified the DOM pool due to microbe-mediated oxidoreduction, with enrichment of heteroatoms (N, S, P) and decreased aromaticity. Microbial community analysis showed SMX pressure significantly stimulated the succession of bacterial structure in both bulk water and rhizospheric biofilms. Furthermore, network analysis further confirmed ROM bio-labile compositions as energy sources and electron shuttles directly influenced microbial structure, thereby facilitating proliferation of antibiotic resistant bacteria (Methylotenera, Sphingobium, Az spirillum) and ARGs (sul1, sul2, intl1). This investigation will provide scientific supports for the control of antibiotic residues and corresponding ARGs in aquatic ecosystems.

Single-cell transcriptome profiling reveals cell type-specific variation and development in HLA expression of human skin.

Skin, the largest organ of body, is a highly immunogenic tissue with a diverse collection of immune cells. Highly polymorphic human leukocyte antigen (HLA) molecules have a central role in coordinating immune responses as recognition molecules. Nevertheless, HLA gene expression patterns among diverse cell types within a specific organ, like the skin, have yet to be thoroughly investigated, with stromal cells attracting much less attention than immune cells. To illustrate HLA expression profiles across different cell types in the skin, we performed single-cell RNA sequencing (scRNA-seq) analyses on skin datasets, covering adult and fetal skin, and hair follicles as the skin appendages. We revealed the variation in HLA expression between different skin populations by examining normal adult skin datasets. Moreover, we evaluated the potential immunogenicity of multiple skin populations based on the expression of classical HLA class I genes, which were well represented in all cell types. Furthermore, we generated scRNA-seq data of developing skin from fetuses of 15 post conception weeks (PCW), 17 PCW, and 22 PCW, delineating the dynamic expression of HLA genes with cell type-dependent variation among various cell types during development. Notably, the pseudotime trajectory analysis unraveled the significant variance in HLA genes during the evolution of vascular endothelial cells. Moreover, we uncovered the immune-privileged properties of hair follicles at single-cell resolution. Our study presents a comprehensive single-cell transcriptomic landscape of HLA genes in the skin, which provides new insights into variation in HLA molecules and offers a clue for allogeneic skin transplantation.

Exosomes derived from mesenchymal stem cells in diabetes and diabetic complications.

Diabetes, a group of metabolic disorders, constitutes an important global health problem. Diabetes and its complications place a heavy financial strain on both patients and the global healthcare establishment. The lack of effective treatments contributes to this pessimistic situation and negative outlook. Exosomes released from mesenchymal stromal cells (MSCs) have emerged as the most likely new breakthrough and advancement in treating of diabetes and diabetes-associated complication due to its capacity of intercellular communication, modulating the local microenvironment, and regulating cellular processes. In the present review, we briefly outlined the properties of MSCs-derived exosomes, provided a thorough summary of their biological functions and potential uses in diabetes and its related complications.

Association of the Neutrophil-to-Lymphocyte Ratio with 90-Day Functional Outcomes in Patients with Acute Ischemic Stroke.

The neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, plays an important role in the inflammatory mechanisms of the pathophysiology and progression of acute ischemic stroke (AIS). The aim of this study was to identify the potential factors associated with functional prognosis in AIS. A total of 303 AIS patients were enrolled in this study; baseline information of each participant, including demographic characteristics, medical history, laboratory data, and 90-day functional outcome, was collected. Multivariate logistic regression analysis revealed that NLR, systolic blood pressure (SBP) and National Institutes of Health Stroke Scale (NIHSS) score were found to be independent factors for poor functional outcomes. Receiver operating characteristic (ROC) curve analysis was performed to estimate the predictive value of the NLR for 90-day functional outcome, with the best predictive cutoff value being 3.06. In the multivariate logistic regression analysis, three models were constructed: Model 1, adjusted for age, sex, SBP, and TOAST classification (AUC = 0.694); Model 2, further adjusted for the NIHSS score at admission (AUC = 0.826); and Model 3, additionally adjusted for the NLR (AUC = 0.829). The NLR at admission was an independent predictor of 90-day prognosis in patients with AIS. The risk factors related to poor 90-day functional outcomes were higher SBP, higher NLR, and a greater NIHSS score.

Improved adaptive regularization for simulated annealing inversion of transient electromagnetic.

Geophysical inversion usually involves ill-posed problem. Regularization is the most commonly used method to mitigate this problem. There are many regularization parameter selection methods, among which the adaptive regularization method can automatically update parameters during iteration, reducing the difficulty of parameter selection. Therefore, it is widely used in linear inversion. However, there are very few studies on the use of adaptive regularization methods in stochastic optimization algorithms. The biggest difficulty is that in stochastic optimization algorithms, the search direction of any iteration is completely random. Data fitting term and stabilizing term vary in a wide range, making it difficult for traditional methods to work. In this paper, we consider the contributions of the data fitting term and the stabilizing term in the objective function and give an improved adaptive regularization method for very fast simulated annealing (VFSA) inversion for transient electromagnetic (TEM) data. The optimized method adjusts the two terms dynamically to make them in balance. We have designed several numerical experiments, and the experimental results demonstrate that the method in this paper not only accelerates the convergence, but also the inversion results are very little affected by the initial regularization parameter. Finally, we apply this method to field data, and the inversion results show very good agreements with nearby borehole data.

Identification of ferroptosis-related subtypes, characteristics of TME infiltration and development of prognostic models in gastric cancer.

BACKGROUND: Ferroptosis is a distinct form of cell death characterized by unique morphology, biochemistry, and genetics, playing a crucial role in the initiation, progression, prognosis, and therapeutic strategies of tumors. However, the impact of ferroptosis-related genes (FRGs) on the tumor microenvironment (TME) remains unclear. This study may advance the existing knowledge of FRGs in gastric cancer, and push ahead with more effective prognostic assessment and the development of more effective immunotherapy approaches. METHODS: FRGs were acquired from the FerrDb database and a consensus clustering technique was adopted to categorize patients with GC into groups in line with the expression profiles of 44 FRGs in order to further investigate the expression properties of these proteins. Assessment of the immune status, microsatellite instability (MSI) and cancer stem cell (CSC) index between the high- and low- risk groups to assess the proportion of TIICs in the TME, ssGSVA was adopted to detect the abundance of infiltrating immune cells from the low-risk and high-risk groups. Expression levels of eight ferroptosis-related genes of prognostic signature in GC tissues and adjacent normal tissues was detected by RT-PCR. RESULTS: In the GC cohort, TP53 has the highest mutation frequency (44 %), and was shown to be highly linked with the expression levels of 11 FRGs. In accordance with the Kaplan-Meier curve, the overall survival time of patients with subtype A (Low FRG-score) discernibly exceeded that of patients with subtype B (High FRG-score).In addition, there is a significant difference in the infiltration of most immune cells between subtype A and subtype B, and some important immune checkpoints (CTLA4, PDCD1, CD274, LAG3, PDCD1LG2, and HAVCR2) have higher expression in cluster A. Finally, low FRG-scores were significantly associated with MSI-H status, while high FRG-scores were significantly associated with microsatellite stable status (MSS). FRG-score is negatively related to the cancer stem cell (CSC). CONCLUSION: Low FRG-score, due to its high microsatellite instability (MSI-H), high mutational load and immune activation, indicates the possible advantage of OS. In addition, the FRG-score was closely related to the cancer stem cell (CSC) index and the sensitive degree of chemotherapeutic drug.

Microplastics induced the differential responses of microbial-driven soil carbon and nitrogen cycles under warming.

The input of microplastics (MPs) and warming interfere with soil carbon (C) or nitrogen (N) cycles. Although the effects of warming and/or MPs on the cycles have been well studied, the biological coupling of microbial-driven cycles was neglected. Here, the synergistic changes of the cycles were investigated using batch incubation experiments. As results, the influences of MPs were not significant at 15, 20, and 25 °C, and yet, high temperature (i.e., 30 °C) reduced the respiration of high-concentration MPs-amended soil by 9.80%, and increased dissolved organic carbon (DOC) by 14.74%. In contrast, high temperature did not change the effect of MPs on N. The decrease of microbial biomass carbon (MBC) and the constant of microbial biomass nitrogen (MBN) indicated that microbial N utilization was enhanced, which might be attributed to the enrichments of adapted populations, such as Conexibacter, Acidothermus, and Acidibacter. These observations revealed that high temperature and MPs drove the differential response of soil C and N cycles. Additionally, the transcriptomic provided genomic evidence of the response. In summary, the high temperature was a prerequisite for the MPs-driven response, which underscored new ecological risks of MPs under global warming and emphasized the need for carbon emission reduction and better plastic product regulation.

A novel tool for tracing water sources of streamflow in a mixed land-use catchment.

Tracing water sources of streamflow in a mixed land-use catchment is critical for predicting pollutant emissions from various human activities to streams but remains a major challenge. A rain event based field monitoring study was conducted in the Jieliu catchment located in the hilly area of central Sichuan Province, southwest China. The ratio of the maximum fluorescence intensities (Fmax) of the two humic-like dissolved organic matter (DOM) components at excitation/emission wavelengths of 255 (315)/415 nm (component 1; C1) and 260 (375)/480 nm (component 2; C2) was proposed as a tracer for quantifying streamflow water sources. Satisfactory performance of using the Fmax(C1)/Fmax(C2) ratio in hydrograph separation of streamflow at the outlet of a forest sub-catchment was verified by through comparison with the hydrograph separation results based on δ18O data. The Fmax(C1)/Fmax(C2) ratio was then applied to estimate the contributions of rainwater and pre-event water sources under different land use types to the streamflow in an agro-forest sub-catchment and the entire catchment. The hydrograph separation results using the Fmax(C1)/Fmax(C2) ratio can be used to support the optimization of water resource management and the quantification of pollutant loadings from major water sources to streams at the catchment scale.

Insights into Dietary Different Co-Forms of Lysine and Glutamate on Growth Performance, Muscle Development, Antioxidation and Related Gene Expressions in Juvenile Grass Carp (Ctenopharyngodon idellus).

The study aimed to compare the effects of crystalline L-lysine and L-glutamate (CAA), Lys-Glu dipeptide (KE) on the growth and muscle development of grass carp (Ctenopharyngodon idellus), and related molecular mechanisms. Five experimental diets (CR, 0.5% CAA, 1.5% CAA, 0.5% KE, 1.5% KE) containing Lys and Glu as free (Lys and Glu, CAA) dipeptide (Lys-Glu, KE) forms were prepared, respectively. A total of 450 juvenile grass carp with an initial weight of 10.69 ± 0.07 g were randomly assigned to 15 cages, and 5 treatments with 3 replicates of 30 fish each for 61 days of feeding. The results showed that the group of 0.5% KE exhibited the best growth performances according to the indicator's weight gain rate (WGR) and specific growth rate (SGR), although no statistically significant occurred among all groups; diet supplemented with 0.5% CAA significantly elevated the condition factor (CF) and viscerasomatic index (VSI) of juvenile grass carp. Diet supplemented with different Lys and Glu co-forms at different levels promoted the muscle amino acid content compared with those of CR group. Comparing with the CR group and other groups, the hardness of 0.5% CAA group significantly increased, and the springiness of 0.5% KE group excelled. Both the muscle fiber diameter and density of 0.5% KE group showed significant difference with those of the CR group, and a negative correlation between them was also observed. To uncover the related molecular mechanism of the differences caused by the different co-forms of Lys and Glu, the effect of different diets on the expressions of protein absorption, muscle quality, and antioxidation-related genes was analyzed. The results suggested that comparing with those of CR group, the dipeptide KE inhibited the expressions of genes associated with protein metabolism, such as AKT, S6K1, and FoxO1a but promoted PCNA expression, while the free style of CAA would improve the FoxO1a expression. Additionally, the muscle development-related genes (MyoD, MyOG, and Myf5) were significantly boosted in CAA co-form groups, and the expressions of fMYHCs were blocked but fMYHCs30 significantly promoted in 0.5% KE group. Finally, the effect of different co-forms of Lys and Glu on muscle antioxidant was examined. The 0.5% CAA diet was verified to increase GPX1a but obstruct Keap1 and GSTP1 expressions, resulting in enhanced SOD activity and reduced MDA levels in plasma. Collectively, the different co-forms of Lys and Glu influenced the growth of juvenile grass carp, and also the muscle development and quality through their different regulation on the protein metabolism, muscle development- and antioxidative-related genes.

From Conversion to Resection for Unresectable Hepatocellular Carcinoma: A Review of the Latest Strategies.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China, accounting for the majority of primary liver cancer cases. Liver resection is the preferred curative method for early-stage HCC. However, up to 80-85% of patients have already missed the opportunity of radical surgery due to tumor advances at the time of consultation. Conversion therapies are a series of medications and treatments for initially inoperable patients. For early-stage unresectable HCC (uHCC) patients, conversion therapies are designed to meet surgical requirements by increasing the volume of the residual liver. Meanwhile, for advanced cases, conversion therapies strive for tumor shrinkage and down-staging, creating the opportunity for liver resection or liver transplantation. This review summarizes the latest advances in conversion therapies and highlights their potential for improving the survival benefit of patients with uHCC.

[Characteristics of Antibiotic Resistance Genes Distribution in Different Types of Agricultural Land Soils in Highly Cultivated Hilly Areas].

To characterize the distribution of antibiotic resistance genes(ARGs) in different types of agricultural soil in highly cultivated hilly areas, the abundance and diversity of ARGs in vegetable, orchard, and arable soils were analyzed in this study. The results showed that 70 ARGs and four mobile genetic elements(MGEs) were detected in all soil samples, with ß-lactam cphA-01 being the most abundant genes in the agricultural soils. In vegetable and orchard soils, the main ARG subtypes were cphA-01 and cmx(A) genes, whereas the mexF and aacC genes were predominant in cropland soils. The relative abundance and diversity of soil ARGs showed that cropland

[Effect of Manure Application on the Adsorption of Antibiotics to Soil].

Sulfonamide antibiotics and florfenicol(FFC) are commonly used antibiotics in Zhejiang Province. They have weak adsorption on soil and are easy to migrate, with high environmental risks. In recent years, most of the studies on the potential risk of fecal-derived antibiotics to farmland soil were conducted by adding manure under laboratory conditions; therefore, it is impossible to assess the risk of antibiotic pollution under natural fertilization. Therefore, batch balance experiments were conducted to explore the effects of different soil types and manure types on the adsorption of antibiotics in the soil, in which five types of dryland farmland soils[Lin'an(LA), Jiashan(JS), Longyou(LY), Kaihua(KH), and Jinhua(JH)]in Zhejiang Province that have been used with different fertilizers(chicken manure, pig manure, and chemical fertilizer) for a long time were chosen, and four types of commonly used antibiotics[sulfadiazine(SD), sulfamethazine(SMT), sulfamethoxazole(SMZ), and FFC]were selected. The results showed that the adsorption of the four antibiotics in the experimental soil was weak, and the adsorption capacity decreased in the order of:SMT(1.44-13.23 mg1-(1/n)·L1/n·kg-1)>SMZ(0.73-6.05 mg1-(1/n)·L1/n·kg-1)>SD(0.16-5.57 mg1-(1/n)·L1/n·kg-1)>FFC(0.27-3.81 mg1-(1/n)·L1/n·kg-1). The Freundlich model was superior to the linear model in fitting the isotherm adsorption of SD, SMT, and FFC, in which SD and FFC belonged to "S" type adsorption, and SMT belonged to "L" type adsorption. For SMZ, the fitting effect of the linear model was better than that of the Freundlich model. The contents of total organic carbon(TOC) and dissolved organic carbon(DOC) could better predict the adsorption capacity of the four antibiotics(r=0.548-0.808), and the values of cation exchange capacity(CEC) and electrical conductivity(EC) could better predict the adsorption capacity of SMT and FFC(r=0.758-0.841). Compared with the application of chemical fertilizer, manure application increased the values of TOC, DOC, CEC, and EC in acidic and neutral soils, which was conducive to the adsorption of antibiotics on the soil. Meanwhile, manure application also increased pH in acidic and neutral soils, which was not conducive to the adsorption of antibiotics on the soil. In addition, manure application reduced the values of TOC, DOC, CEC, EC, and pH in alkaline soils. The lower pH was conducive to antibiotic adsorption on the soil, whereas the lower content of the other four was not conducive to antibiotic adsorption on the soil. For the acidic soil with low fertility, the application of manure increased soil fertility and thus increased the adsorption of antibiotics on the soil, such as the LA soil with chicken manure, the LY(1) soil with pig manure, and the JH soil with chicken manure and pig manure. However, for the acidic and neutral soils with high fertility, the application of manure had significantly increased soil pH and thus reduced the adsorption of antibiotics on the soil, such as the JS soil with chicken manure and pig manure and the LY(2) soil with chicken manure. For calcareous soil with high fertility and pH(such as KH soil), the adsorption profiles of the four types of antibiotics on the soil showed diversity after the application of manure:the adsorption capacity of SD increased significantly after the application of chicken manure and pig manure, whereas the adsorption capacity of SMT and SMZ decreased significantly, and the adsorption capacity of FFC declined significantly after the application of chicken manure. Therefore, manure application according to soil fertility could effectively control the environmental risk of fecal antibiotics.

Axial length shortening in myopic children with Stickler syndrome after repeated low-level red-light therapy.

AIM: To report the myopia-controlling effect of repeated low-level red-light (RLRL) therapy in patients with Stickler syndrome (STL), an inherited collagenic disease typically presenting with early onset myopia. METHODS: Three STL children, aged 3, 7, and 11y, received RLRL therapy throughout the follow-up period of 17, 3, and 6mo, respectively after exclusion of fundus anomalies. Data on best-corrected visual acuity (BCVA), intraocular pressure, cycloplegic subjective refraction, ocular biometrics, scanning laser ophthalmoscope, optical coherence tomography, genetic testing, systemic disease history, and family history were recorded. RESULTS: At the initiation of the RLRL therapy, the spherical equivalent (SE) of 6 eyes from 3 patients ranged from -3.75 to -20.38 D, axial length (AL) were from 23.88 to 30.68 mm, and BCVA were from 0.4 to 1.0 (decimal notation). Myopia progression of all six eyes slowed down after RLRL therapy. AL in five out of the six eyes shortened -0.07 to -0.63 mm. No side effects were observed. CONCLUSION: Three cases of STL whose progression of myopic shift and AL elongation are successfully reduced and even reversed after RLRL therapy.

Fine particulate matter promotes airway inflammation and mucin production by activating endoplasmic reticulum stress and the IRE1α/NOD1/NF­κB pathway.

Fine particulate matter (PM2.5) is a type of small particle that is <2.5 µm in diameter that may cause airway inflammation. Thus, the present study aimed to explore the effects of PM2.5 on endoplasmic reticulum (ER) stress and airway inflammation in human airway epithelial cells. For this purpose, HBE135­E6E7 airway epithelial cells were cultured and exposed to specific concentrations of PM2.5 for various periods of time, and cell viability was determined using a Cell Counting Kit­8 assay. The results of the present study demonstrated that exposure to PM2.5 increased the mRNA and protein expression levels of interleukin (IL)­6, tumor necrosis factor (TNF)­α and mucin 5AC (MUC5AC). Moreover, the expression levels of ER stress­related proteins, such as glucose­regulated protein 78, CCAAT­enhancer binding protein homologous protein, activating transcription factor 6, protein kinase R­like ER kinase (PERK), phosphorylated (p­)PERK, inositol­requiring enzyme 1α (IRE1α) and p­IRE1α, and nucleotide­binding oligomerization domain 1 (NOD1) expression levels were increased following exposure to PM2.5. Transfection with IRE1α small interfering RNA (siRNA) led to the increased production of IL­6, TNF­α and MUC5AC. Moreover, the expression of NOD1 and the translocation of NF­κB p65 were inhibited following transfection with IRE1α siRNA. In addition, the results of the present study demonstrated that transfection with NOD1 siRNA decreased the production of IL­6, TNF­α and MUC5AC, and decreased the translocation of NF­κB p65. The expression levels of IL­6, TNF­α and MUC5AC were increased in the HBE135­E6E7 cells following treatment with C12­iE­DAP, a NOD1 agonist. Moreover, treatment with C12­iE­DAP led to the activation of NF­κB p65. Collectively, the results of the present study suggest that PM2.5 promotes airway inflammation and mucin production by activating ER stress in HBE135­E6E7 airway epithelial cells, and that the IRE1α/NOD1/NF­κB pathway may be involved in this process.

[Neuroprotective effect and mechanism of cPLA2 inhibitor increases autophagic flux on spinal cord injury].

OBJECTIVE: To investigate the mechanism of cytosolic phospholipase A2(cPLA2) inhibitor to improve neurological function after spinal cord injury (SCI). METHODS: Thirty-six 3 months old female SD rats, with body mass (280±20) g, were divided into three groups (n=12):sham group, SCI group, and SCI+ arachidonyl trifluoromethyl ketone(AACOCF3) group. Balloon compression SCI model was established in all three groups. In the sham model group, the spinal cord compression model was created after the balloon was placed without pressure treatment, and the remaining two groups were pressurized with the balloon for 48 h. After successful modeling, rats in the SCI+AACOCF3 group were injected intraperitoneally with AACOCF3, a specific inhibitor of cPLA2. The remaining two groups of rats were injected intraperitoneally with saline. The animals were sacrificed in batches on 7 and 14 days after modeling, respectively. And the damaged spinal cord tissues were sampled for pathomorphological observation, to detect the expression of cPLA2 and various autophagic fluxPrelated molecules and test the recovery of motor function. RESULTS: Spinal cord histomorphometry examination showed that the spinal cord tissue in the sham group was structurally intact, with normal numbers and morphology of neurons and glial cells. In the SCI group, spinal cord tissue fractures with large and prominent spinal cord cavities were seen. In the SCI+AACOCF3 group, the spinal cord tissue was more intact than in the SCI group, with more fused spinal cord cavities, more surviving neurons, and less glial cell hyperplasia. Western blot showed that the sham group had the lowest protein expression of LC3-Ⅱ, Beclin 1, p62, and cPLA2 compared with the SCI and SCI+AACOCF3 groups (P<0.05) and the highest protein expression of LC3-Ⅰ (P<0.05). P62 and cPLA2 expression in the SCI group were higher than in the SCI+AACOCF3 group (P<0.05). Behavioral observations showed that the time corresponding to BBB exercise scores was significantly lower in both the SCI and SCI+AACOCF3 groups than in the sham group (P<0.05). Scores at 3, 7, and 14 days after pressurization were higher in the SCI+AACOCF3 group than in the SCI group (P<0.05). CONCLUSION: cPLA2 inhibitors can reduce neuronal damage secondary to SCI, promote neurological recovery and improve motor function by improving lysosomal membrane permeability and regulating autophagic flux.

PIEZO1 is downregulated in glenohumeral chondrocytes in early cuff tear arthropathy following a massive rotator cuff tear in a mouse model.

Introduction: A massive rotator cuff tear (RCT) leads to glenohumeral joint destabilization and characteristic degenerative changes, termed cuff tear arthropathy (CTA). Understanding the response of articular cartilage to a massive RCT will elucidate opportunities to promote homeostasis following restoration of joint biomechanics with rotator cuff repair. Mechanically activated calcium-permeating channels, in part, modulate the response of distal femoral chondrocytes in the knee against injurious loading and inflammation. The objective of this study was to investigate PIEZO1-mediated mechanotransduction of glenohumeral articular chondrocytes in the altered biomechanical environment following RCT to ultimately identify potential therapeutic targets to attenuate cartilage degeneration after rotator cuff repair. Methods: First, we quantified mechanical susceptibility of chondrocytes in mouse humeral head cartilage ex vivo with treatments of specific chemical agonists targeting PIEZO1 and TRPV4 channels. Second, using a massive RCT mouse model, chondrocytes were assessed for mechano-vulnerability, PIEZO1 expression, and calcium signaling activity 14-week post-injury, an early stage of CTA. Results: In native humeral head chondrocytes, chemical activation of PIEZO1 (Yoda1) significantly increased chondrocyte mechanical susceptibility against impact loads, while TRPV4 activation (GSK101) significantly decreased impact-induced chondrocyte death. A massive RCT caused morphologic and histologic changes to the glenohumeral joint with decreased sphericity and characteristic bone bruising of the posterior superior quadrant of the humeral head. At early CTA, chondrocytes in RCT limbs exhibit a significantly decreased functional expression of PIEZO1 compared with uninjured or sham controls. Discussion: In contrast to the hypothesis, PIEZO1 expression and activity is not increased, but rather downregulated, after massive RCT at the early stage of cuff tear arthropathy. These results may be secondary to the decreased axial loading after glenohumeral joint decoupling in RCT limbs.

The recurrent WASF1 nonsense variant identified in two unaffected Chinese families with neurodevelopmental disorder: case report and review of the literatures.

BACKGROUND: Neurodevelopmental disorder with absent language and variable seizures (NEDALVS, # 618707) are characterized by delayed speech and motor development, ocular abnormalities, and seizures. NEDAVLS is an autosomal dominant disorder caused by de novo mutations in the wasp protein family member 1 (WASF1) gene. CASE PRESENTATION: We identified a de novo nonsense variant c.1516 C > T (p.Arg506*) of WASF1 gene (NM_003931.3) in two pediatric female patients with delayed motor and language development. CONCLUSION: This case demonstrates the effective role of WES in the diagnosis of NEDALVS. To the best of our knowledge, this variant has not been reported in the Chinese population. This contributes to our further understanding of the disease and to research related to the genetic and clinical heterogeneity, the treatment and prognosis of the disease.

HDAC-an important target for improving tumor radiotherapy resistance.

Radiotherapy is an important means of tumor treatment, but radiotherapy resistance has been a difficult problem in the comprehensive treatment of clinical tumors. The mechanisms of radiotherapy resistance include the repair of sublethal damage and potentially lethal damage of tumor cells, cell repopulation, cell cycle redistribution, and reoxygenation. These processes are closely related to the regulation of epigenetic modifications. Histone deacetylases (HDACs), as important regulators of the epigenetic structure of cancer, are widely involved in the formation of tumor radiotherapy resistance by participating in DNA damage repair, cell cycle regulation, cell apoptosis, and other mechanisms. Although the important role of HDACs and their related inhibitors in tumor therapy has been reviewed, the relationship between HDACs and radiotherapy has not been systematically studied. This article systematically expounds for the first time the specific mechanism by which HDACs promote tumor radiotherapy resistance in vivo and in vitro and the clinical application prospects of HDAC inhibitors, aiming to provide a reference for HDAC-related drug development and guide the future research direction of HDAC inhibitors that improve tumor radiotherapy resistance.