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BackgroundProtein Energy Wasting (PEW) has high incidence in adult hemodialysis patients and refers to a state of decreased protein and energy substance. It has been demonstrated that PEW highly affects the quality of survival and increases the risk of death. Nevertheless, its diagnostic criteria are complex in clinic. To simplify the diagnosis method of PEW in adult hemodialysis patients, we previously established a novel clinical prediction model that was well-validated internally using bootstrapping. In this multicenter cross-sectional study, we aimed to externally validate this nomogram in a new cohort of adult hemodialysis patients.MethodsThe novel prediction model was built by combining four independent variables with part of the International Society of Renal Nutrition and Metabolism (ISRNM) diagnostic criteria including albumin, total cholesterol, and body mass index (BMI). We evaluated the performance of the new model using discrimination (Concordance Index), calibration plots, and Clinical Impact Curve to assess its predictive utility.ResultsFrom September 1st, 2022 to August 31st, 2023, 1,158 patients were screened in five medical centers in Shanghai. 622 (53.7%) hemodialysis patients were included for analysis. The PEW predictive model was acceptable discrimination with the area under the curve of 0.777 (95% CI 0.741–0.814). Additionally, the model revealed well-fitted calibration curves. The McNemar test showed the novel model had similar diagnostic efficacy with the gold standard diagnostic method (p > 0.05).ConclusionOur results from this cross-sectional external validation study further demonstrate that the novel model is a valid tool to identify PEW in adult hemodialysis patients effectively.

Purpose: Pathological fibrosis of the myodural bridge (MDB) affects cerebrospinal fluid circulation. However, no optimal drug treatments are available. We aimed to explore the antifibrotic effect of resveratrol on bleomycin-induced pathological fibrosis of the MDB and its underlying mechanisms. Methods: Genes common to the potential targets of resveratrol were determined using network pharmacology, genes related to muscle and tendon fibrosis were acquired from the GeneCards database, and genes related to MDB development were determined using Venny. These genes were considered potential resveratrol treatment targets in bleomycin-induced pathological fibrosis of the MDB and were annotated using bioinformatics methods. We validated the intersected genes using quantitative real-time polymerase chain reaction (qRT-PCR) and performed molecular docking analysis to calculate the binding activity between the target gene and resveratrol. Hematoxylin and eosin and Masson staining were used to detect the morphological changes in bleomycin-induced fibrosis of the MDB following resveratrol treatment. We used qRT-PCR and immunohistochemistry to evaluate the expression of the sirtuin 3 (SIRT3)/transforming growth factor-β1 (TGF-β1)/Smad pathway and the profibrotic markers α-smooth muscle actin (α-SMA) and Collagen Ⅰ. Results: Through network pharmacology and bioinformatics analyses, we identified four core intersected genes, and SIRT3 expression was validated using qRT-PCR. Molecular docking analysis revealed that resveratrol had good binding affinity for SIRT3. Resveratrol ameliorated morphological abnormalities in bleomycin-induced pathological fibrosis of the MDB by inhibiting fibroblast activation and excessive collagen fiber deposition. Resveratrol exerted its antifibrotic effect by regulating the SIRT3/TGF-β1/Smad pathway. Conclusion: Resveratrol has an antifibrotic effect in bleomycin-induced pathological fibrosis of the MDB in vivo and may be considered a novel therapeutic strategy.

BackgroundPoint-of-care Testing (POCT) glycosylated hemoglobin (HbA1c) is a convenient, cheap, effective and accessible screening method for type 2 diabetes in rural areas and community settings that is widely used in the European region and Japan, but not yet widespread in China. The study is the first to evaluate the cost-effectiveness of POCT HbA1c, fasting capillary glucose (FCG), and venous blood HbA1c to screen for type 2 diabetes in urban and rural areas of China, and to identify the best socio-economically beneficial screening strategy.MethodsBased on urban and rural areas in China, economic models for type 2 diabetes screening were constructed from a social perspective. The subjects of this study were adults aged 18–80 years with undiagnosed type 2 diabetes. Three screening strategies were established for venous blood HbA1c, FCG and POCT HbA1c, and cost-effectiveness analysis was performed by Markov models. One-way sensitivity analysis and probabilistic sensitivity analysis were performed on all parameters of the model to verify the stability of the results.ResultsCompared with FCG, POCT HbA1c was cost-effective with an incremental cost-utility ratio (ICUR) of $500.06/quality-adjusted life year (QALY) in urban areas and an ICUR of $185.10/QALY in rural areas, within the willingness-to-pay threshold (WTP = $37,653). POCT HbA1c was cost-effective with lower cost and higher utility compared with venous blood HbA1c in both urban and rural areas. In the comparison of venous blood HbA1c and FCG, venous blood HbA1c was cost-effective (ICUR = $20,833/QALY) in urban areas but not in rural areas (ICUR = $41,858/QALY). Sensitivity analyses showed that the results of the study were stable and credible.ConclusionsPOCT HbA1c was cost-effective for type 2 diabetes screening in both urban and rural areas of China, which could be considered for future clinical practice in China. Factors such as geographic location, local financial situation and resident compliance needed to be considered when making the choice of venous blood HbA1c or FCG.

Polypropylene (PP) is considered to be a rather promising material for HVDC cable insulation. Grafting modi-fication has proved to be an effective method on the electrical property improvements of PP. This paper reports on the highly-enhanced electrical properties of styrene-grafted polypropylene (PP-g-St) and their related mechanism. The influence of grafting styrene on crystallization structures, thermal properties and electrical properties of PP-g-St are characterized and analyzed. These results show that PP-g-St exhibits remarkably enhanced DC volume resistivity, suppressed space charge accumulation and improved DC breakdown strengths as compared to PP. Crystallization observation shows PP-g-St has small, imperfect spherulites with indistinct boundaries, which is strongly correlated to enhanced electrical properties. This study provides an effective grafting strategy to design high-performance HVDC cable insulation materials for bulk power transmission systems.

Abstract Background Lung cancer is a highly prevalent malignancy and has the highest mortality rate among all tumors due to lymph node metastasis. Bone marrow and umbilical cord-derived mesenchymal stem cells (MSCs) have demonstrated tumor-suppressive effects on lung cancer. This study investigated the effects of DPSC lysate on proliferation, apoptosis, migration and invasion of cancer cells were studied in vivo and in vitro. Methods The proliferation, apoptosis, and migration/metastasis were evaluated by cell counting kit-8 assay, Annexin-V and propidium iodide staining, and the transwell assay, respectively. The expression levels of apoptosis-, cell cycle-, migration-, and adhesion-related mRNA and proteins were measured by qRT-PCR and western blot. The level and mRNA expression of tumor markers carcino embryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) were measured by Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR. Finally, a tumor-bearing mouse model was constructed to observe the tumor-suppressive effect of DPSC lysate after intraperitoneal injection. Results DPSC lysate decreased the viability of A549 cells and induced apoptosis in lung cancer cells. Western blot confirmed that levels of Caspase-3, Bax, and Bad were increased, and Bcl-2 protein levels were decreased in A549 cells treated with DPSC lysate. In addition, DPSC lysate inhibited the migration and invasion of A549 cells; downregulated key genes of the cell cycle, migration, and adhesion; and significantly suppressed tumor markers. Xenograft results showed that DPSC lysate inhibited tumor growth and reduced tumor weight. Conclusions DPSC lysate inhibited proliferation, invasion, and metastasis; promoted apoptosis in lung cancer cells; and suppressed tumor growth- potentially providing a cell-based alternative therapy for lung cancer treatment. Graphical Abstract

AbstractContext Salvia miltiorrhizae Bunge (Lamiaceae) is a traditional Chinese medicine (TCM) for the treatment of ‘thoracic obstruction’. Transient receptor potential canonical channel 1 (TRPC1) is a important target for myocardial injury treatment.Objective This work screens the active component acting on TRPC1 from Salvia miltiorrhizae.Materials and methods TCM Systems Pharmacology Database and Analysis Platform (TCMSP) was used to retrieve Salvia miltiorrhiza compounds for preliminary screening by referring to Lipinski’s rule of five. Then, the compound group was comprehensively scored by AutoDock Vina based on TRPC1 protein. Surface plasmon resonance (SPR) was used to determine the affinity of the optimal compound to TRPC1 protein. Western blot assay was carried out to observe the effect of the optimal compound on TRPC1 protein expression in HL-1 cells, and Fura-2/AM detection was carried out to observe the effect of the optimal compound on calcium influx in HEK293 cells.Results Twenty compounds with relatively good characteristic parameters were determined from 202 compounds of Salvia miltiorrhiza. Rosmarinic acid (RosA) was obtained based on the molecular docking scoring function. RosA had a high binding affinity to TRPC1 protein (KD value = 1.27 µM). RosA (50 μM) could reduce the protein levels (417.1%) of TRPC1 after oxygen-glucose deprivation/reperfusion (OGD/R) in HL-1 cells and it could inhibit TRPC1-mediated Ca2+ influx injury (0.07 ΔRatio340/380) in HEK293 cells.Discussion and conclusions We obtained the potential active component RosA acting on TRPC1 from Salvia miltiorrhizae, and we speculate that RosA may be a promising clinical candidate for myocardial injury therapy.

BackgroundTislelizumab, a humanized IgG4 anti-PD-1 monoclonal antibody has been approved in China and Europe. According to the published clinical research, tislelizumab shows satisfactory safety profile. No severe hepatotoxicity or acute kidney injury were reported.Case presentationWe presented a case study of a 74-year-old man who developed acute kidney injury (grade 3) and acute liver injury (grade 4) after being administered tislelizumab for the treatment of esophageal squamous cell carcinoma. We reviewed the patient’s history, physical examination, and laboratory findings and provided comprehensive differentials of the possible causes of the toxicities. Immune Checkpoint Inhibitors (ICI) hepatotoxicity and nephrotoxicity were confirmed clinically. We also discussed the management of toxicities associated with ICIs and the need for a multidisciplinary approach to care.ConclusionsThe case highlights the importance of close monitoring and prompt management of toxicities associated with ICIs and the need for further research to better understand the risk factors for these toxicities and to identify effective treatments for them.

Thyroid-associated ophthalmopathy(TAO)is an autoimmune inflammatory disease involving multiple orbital tissues with a variety of clinical manifestations, which has serious effects on the life quality of patients.Interventions of TAO mainly include medical treatment to stabilize thyroid function, reduce inflammation and regulate immune function, as well as surgical treatment to relieve ocular symptoms. Botulinum toxin type A can paralyze muscles by blocking nerve impulse conduction at the neuromuscular junction, which is of certain therapeutic value for restrictive strabismus due to extraocular muscle involvement and upper eyelid retraction due to involvements of levator palpebrae superioris and Müller's muscle in TAO patients, especially when they have surgical contraindications, lack surgical opportunity, or refuse surgery. This paper reviews the application of botulinum toxin type A in the treatment of TAO, focusing on its pharmacological mechanism, dosage, effectiveness, and possible complications when treating restrictive strabismus and upper eyelid retraction, and discussing potential therapeutic values of botulinum toxin type A for intraocular pressure elevation, glabellar frown lines and dry eye caused by extraocular muscle compression in TAO patients, in order to provide a reference for clinical intervention.

Dioscorea alata, commonly known as “greater yam”, is a vital crop in tropical and subtropical regions of the world, yet it faces significant threats from anthracnose disease, mainly caused by Colletotrichum gloeosporioides. However, exploring disease resistance genes in this species has been challenging due to the difficulty of genetic mapping resulting from the loss of the flowering trait in many varieties. The receptor-like kinase (RLK) gene family represents essential immune receptors in plants. In this study, genomic analysis revealed 467 RLK genes in D. alata. The identified RLKs were distributed unevenly across chromosomes, likely due to tandem duplication events. However, a considerable number of ancient whole-genome or segmental duplications dating back over 100 million years contributed to the diversity of RLK genes. Phylogenetic analysis unveiled at least 356 ancient RLK lineages in the common ancestor of Dioscoreaceae, which differentially inherited and expanded to form the current RLK profiles of D. alata and its relatives. The analysis of cis-regulatory elements indicated the involvement of RLK genes in diverse stress responses. Transcriptome analysis identified RLKs that were up-regulated in response to C. gloeosporioides infection, suggesting their potential role in resisting anthracnose disease. These findings provide novel insights into the evolution of RLK genes in D. alata and their potential contribution to disease resistance.

Abstract The production of plastic and the amount of waste plastic that enters the ecosystem increases every year. Synthetic plastics gradually break down into particles on the micro- and nano-scale in the environment. The micro- and nano-plastics pose a significant ecological threat by transporting toxic chemicals and causing inflammation and cellular damage when ingested; however, removal of those particles from water is challenging using conventional separation methods. Deep eutectic solvents (DES), a new class of solvents composed of hydrogen bond donors and acceptors, have been proposed as a cheaper alternative to ionic liquids. Hydrophobic DES derived from natural compounds (NADES) show promise as extractants in liquid–liquid extractions. This study investigated the extraction efficiency of micro- and nano-plastics including polyethylene terephthalate, polystyrene, and a bioplastic polylactic acid from fresh water and saltwater using three hydrophobic NADES. The extraction efficiencies fall in a range of 50–93% (maximum % extraction) while the extraction rates fall between 0.2 and 1.3 h (as indicated by the time to extract half the theoretical maximum). Molecular simulations show a correlation between the extraction efficiency and the association between the plastics and NADES molecules. This study demonstrates the potential of hydrophobic NADES as extractants for removal of different micro- and nano-plastic particles from aqueous solutions.

AbstractPurpose Due to the poor and unpredictable prognosis of breast cancer (BC) patients with bone metastasis, it is necessary to find convenient and available prognostic predictors. This study aimed to recognize the clinical and prognostic factors related to clinical laboratory examination and to construct a prognostic nomogram for BC bone metastasis.Methods We retrospectively analyzed 32 candidate indicators from clinical features and laboratory examination data of 276 BC patients with bone metastasis. Univariate and multivariate regression analyses were performed to identify significant prognostic factors related to BC with bone metastasis. Nomogram was constructed and estimated by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis.Results Patients were randomly grouped into training (n = 197) and validation cohorts (n = 79). In training cohort, the multivariate regression analysis revealed that age, other organ metastasis sites, serum level of lactate dehydrogenase, globulin, white blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, and monocyte ratio were independent prognostic factors for BC with bone metastasis. The prognostic nomogram in training cohort exhibited areas under the ROC curve (AUCs) of 0.797, 0.782, and 0.794, respectively, for predicting 1-, 3-, and 5-year overall survival. In validation cohort, the nomogram still showed acceptable discrimination ability (AUCs: 0.723, 0.742, and 0.704) and calibration.Conclusion This study constructed a novel prognostic nomogram for BC patients with bone metastasis. It could serve as a potential tool of survival assessment to help individual treatment decision-making for clinicians.

Metastasis of lung adenocarcinoma (LUAD) is a major cause of death in patients. Aryl hydrocarbon receptor (AHR), an important transcription factor, is involved in the initiation and progression of lung cancer. Polo-like kinase 1 (PLK1), a serine/threonine kinase, acts as an oncogene promoting the malignancy of multiple cancer types. However, the interaction between these two factors and their significance in lung cancer remain to be determined. In this study, we demonstrate that PLK1 phosphorylates AHR at S489 in LUAD, leading to epithelial-mesenchymal transition (EMT) and metastatic events. RNA-seq analyses reveal that type 2 deiodinase (DIO2) is responsible for EMT and enhanced metastatic potential. DIO2 converts tetraiodothyronine (T4) to triiodothyronine (T3), activating thyroid hormone (TH) signaling. In vitro and in vivo experiments demonstrate that treatment with T3 or T4 promotes the metastasis of LUAD, whereas depletion of DIO2 or a deiodinase inhibitor disrupts this property. Taking together, our results identify the AHR phosphorylation by PLK1 and subsequent activation of DIO2-TH signaling as mechanisms leading to LUAD metastasis. These findings can inform possible therapeutic interventions for this event.

In this study, the influence of repair welding on microstructure evolution, mechanical properties, and corrosion resistance of SUS304-Q345B dissimilar metal active gas arc (MAG) welding plates was investigated via optical microscopy (OM), scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), hardness, tensile, fatigue, intergranular corrosion, and electrochemical tests, in which the zero (R0), primary (R1), and secondary repair welding (R2) were performed by MAG welding. The results showed that, after repair welding, the δ-ferrite morphology in the weld evolved from a continuous dendritic shape to a dispersed worm-like structure and the bar ferrite in the heat-affected zone of SUS304 (HAZSUS304) evolved into short bar ferrite. The grain size of the weld was reduced due to the remelting caused by repair welding. The hardness of the weld increased first and then decreased which was related to the decrease of δ-ferrite morphology and grain size of weld. In the tensile test, all specimens were fractured at Q345B base material (BMQ345B), which revealed that repair welding had little effect on the tensile properties. The fatigue limit strength of R1 didn't reduce significantly, while the fracture position of R2 transferred from the SUS304 base material (BMSUS304) to the fusion line of SUS304 (FLSUS304). The corrosion resistance of R1 weld possessed the best corrosion resistance owing to the finer grain size and better δ-ferrite morphology. The results indicated that repair welding was feasible for the repair and reuse of welded joints, and it was of great importance in engineering applications of welded plates.

Similar to Si3N4 ceramics, β→α phase transformation in SiC ceramics plays a key role in tailoring the microstructures thus optimizing related properties. SiC microstructures are dominated with the core–rim structures by AlN-solution, and by EBSD analysis, α-lamellae were revealed as stacking-faults (SF) and twin-boundaries (TB) in β-grains, co-existing with the core–rim structures as α/β→α’/β’ transformation by sintering. The structural transformation can proceed much further by gas-pressure-sintering than hot-pressing with only RE2O3 agents, while the latter retain a high-density of SF/TB in the metastable β-SiC grains. By high-angle secondary-electron imaging, nanoscale transition-layer (TL) was observed as an inter-phase to fully separate the core and rim, which is created by a transitory equilibrium in the solution–reprecipitation process. The enrichment of AlN or RE in TL demonstrates their segregation to core surface until reaching the super-saturation and before the growth of rims. With higher AlN or RE solution and after sintering, a shear stress can develop from TL contour to drive the expansion of SF/TB in Martensitic transition, especially under an external isotropic pressure. The combinations of β→α transformation, core–rim structures and viscous liquid-phase enable the comprehensive assessment of sintering–microstructure–property–performance relationship of SiC ceramics, as demonstrated for their creep behaviors and fracture toughness.

Solid oxide electrolysis cell (SOEC) industrialization has been developing for many years. Commercial materials such as 8 mol% Y2O3-stabilized zirconia (YSZ), Gd0.1Ce0.9O1.95 (GDC), La0.6Sr0.4Co0.2Fe0.8O3−δ (LSCF), La0.6Sr0.4CoO3−δ (LSC), etc., have been used for many years, but the problem of mismatched thermal expansion coefficients of various materials between cells has not been fundamentally solved, which affects the lifetime of SOECs and restricts their industry development. Currently, various solutions have been reported, such as element doping, manufacturing defects, and introducing negative thermal expansion coefficient materials. To promote the development of the SOEC industry, a direct treatment method for commercial materials—quenching and doping—is reported to achieve the controllable preparation of the thermal expansion coefficient of commercial materials. The quenching process only involves the micro-treatment of raw materials and does not have any negative impact on preparation processes such as powder slurry and sintering. It is a simple, low-cost, and universal research strategy to achieve the controllable preparation of the thermal expansion coefficient of the commercial material La0.6Sr0.4Co0.2Fe0.8O3−δ (LSCF) through a quenching process by doping elements and increasing oxygen vacancies in the material. Commercial LSCF materials are heated to 800 °C in a muffle furnace, quickly removed, and cooled and quenched in 3.4 mol/L of prepared Y(NO3)3. The thermal expansion coefficient of the treated material can be reduced to 13.6 × 10−6 K−1, and the blank sample is 14.1 × 10−6 K−1. In the future, it may be possible to use the quenching process to select appropriate doping elements in order to achieve similar thermal expansion coefficients in SOECs.

Sodium- (Na+) and potassium- (K+) ion batteries are cost-effective alternatives to lithium-ion (Li+) batteries due to the abundant sodium and potassium resources. Solid polymer electrolytes (SPEs) are essential for safer and more efficient Na+ and K+ batteries because they often exhibit low ionic conductivity at room temperature. While zwitterionic (ZW) materials enhance Li+ battery conductivity, their potential for Na+ and K+ transport in batteries remains unexplored. In this study, we investigated the effect of three ZW molecules (ChoPO4, i.e., 2-methacryloyloxyethyl phosphorylcholine, ImSO3, i.e., sulfobetaine ethylimidazole, and ImCO2, i.e., carboxybetaine ethylimidazole) on the dissociation of Na+ and K+ coordination with ethylene oxide (EO) chains in EO-based electrolytes through molecular dynamics simulations. Our results showed that ChoPO4 possessed the highest cation–EO10 dissociation ability, while ImSO3 exhibited the lowest. Such dissociation ability correlated with the cation–ZW molecule coordination strength: ChoPO4 and ImSO3 showed the strongest and the weakest coordination with cations. However, the cation–ZW molecule coordination could slow the cationic diffusion. The competition of these effects resulted in accelerating or decelerating cationic diffusion. Our simulated results showed that ImCO2 enhanced Na+ diffusion by 20%, while ChoPO4 and ImSO3 led to a 10% reduction. For K+, ChoPO4 reduced its diffusion by 40%, while ImCO2 and ImSO3 caused a similar decrease of 15%. These findings suggest that the ZW structure and the cationic size play an important role in the ionic dissociation effect of ZW materials.

Abstract Background Anatomic repair of anterior talofibular ligament (ATFL) is used to manage chronic lateral ankle instability (CLAI). However, the optimal suture configuration used to repair the ATFL is not yet determined. It remains unclear whether suture configuration affects clinical outcomes in such patients. Purpose To compare the functional outcomes of all-inside arthroscopic ATFL repair using either a loop suture and or a free-edge suture configuration in CLAI patients. Study Design Cohort study; Level of evidence, 3. Methods This retrospective cohort study included 71 patients with CLAI who had undergone an all-inside arthroscopic ATFL repair procedure with either loop suture (n = 36) or free-edge suture (n = 35) from February 2016 to July 2018. Comparable pre-operatively, the Visual analogy score (VAS), American Orthopedic Foot and Ankle Society scoring system (AOFAS), Karlsson Ankle Functional Score (KAFS) scoring system, Anterior Talar Translation (ATT) and Active Joint Position Sense (AJPS) were used to evaluate postoperative ankle function. Results There were no postoperative wound complications, implant reactions, or neurological or vascular injuries. Postoperative hospitalization, VAS, AOFAS, KAFS, AJPS and the time of return to sport were similar between the loop suture group and free-edge suture group. Requiring a longer procedure time, patients with loop suture configuration achieved better ATT. Conclusion All-inside arthroscopic ATFL repair procedure for CLAI treatment provides better ATT and comparable functional outcomes when a loop suture configuration is used instead of a free-edge suture configuration. A statistical difference in ATT was observed. Given the relatively short follow-up, it is questionable whether this will have any clinical relevance.

Abstract Although oral probiotics can improve breast microecology and alleviate the inflammatory response, there are no data regarding cases with existing abscesses. We aimed to investigate the effect of Lactobacillus fermentum CECT5716 during needle aspiration in patients with lactational breast abscesses. Patients (aged 20–41 years) with lactational single-cavity breast abscesses (diameter 3–6 cm) from 12 hospitals were randomly assigned to the experimental (n = 51) and control groups (n = 50). Outcome measures included the abscess cure rate on treatment day-5, delactation rate, relieving pain rate, and number of needle aspirations until day-28. The experimental group’s 5-day cure rate (43.1%) was significantly higher (p

Purpose To explore the current research about the role of optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) in dysthyroid optic neuropathy (DON).Methods Studies in the literature that focused on OCT, OCTA and DON were retrieved by searching PubMed, EMBASE, Cochrane databases and Clinical Trial before 20 June 2023. The methodological quality was assessed using the Newcastle-Ottawa scale. The quantitative calculation was performed using Review Manager V.5.3.Results Twelve studies met the eligibility criteria and were included. DON group presented lower macular ganglion cell complex in the overall, superior and inferior hemifields compared with the non-DON group. Furthermore, the ganglion cell layer and inner plexiform layer in DON group was thinner in contrast to the non-DON group. The optic nerve head vessel density was lower in the DON group than that in the non-DON group. A reduction of radial peripapillary capillary vessel density could be seen in the DON group than the non-DON group in overall, inside disc, peripapillary, superior-hemifield, temporal and nasal. Besides, the macular superficial retinal capillary layer of non-DON and DON is lower than the healthy control group.Conclusions This study supported the potential value of OCT and OCTA metrics as novel biomarkers of DON. Ophthalmologists should comprehensively consider the retinal structure and microvasculature in dealing with DON.Ethics and dissemination This systematic review included data from published literature and was exempt from ethics approval. Results would be disseminated through peer-reviewed publication and presented at academic conferences engaging clinicians.PROSPERO registration number CRD42023414907.

PurposeThe present study aimed to identify clinicopathological characteristics of breast cancer liver metastasis (BCLM) as well as to characterize the risk and prognostic factors for the liver metastasis (LM) of breast cancer patients with de novo and relapsed distant metastasis in a Chinese population.Materials and methodsPatients with metastatic breast cancer (MBC) who were hospitalized in the Breast Cancer Center at Chongqing University between January 2011 and December 2019 were included in the present study. Logistic regression analyses were conducted to identify risk factors for the presence of BCLM. Cox proportional hazard regression models were performed to determine the prognostic factors for the survival of BCLM patients. The correlation between LM and overall survival was assessed by the Kaplan–Meier method.ResultsIn total, 1,228 eligible MBC patients, including 325 cases (26.5%) with de novo metastasis (cohort A) and 903 cases (73.5%) with relapsed metastasis (cohort B), were enrolled in the present study. In cohort A and cohort B, 81 (24.9%) and 226 (25.0%) patients had BCLM, respectively. Patients in these two cohorts had different clinicopathological features. Logistic regression analysis identified that the human epidermal growth factor receptor 2 (HER2) status in cohort A as well as the HER2 status and invasive ductal carcinoma histology in cohort B were risk factors for BCLM. The median OS of patients with LM was inferior to that of non-LM patients (17.1 vs. 37.7 months, P = 0.0004 and 47.6 vs. 84.0 months, P < 0.0001, respectively). Cox analysis identified that the primary T stage, Ki67 level, and breast surgery history were independent prognostic factors for cohorts A and B, respectively.ConclusionsDe novo and relapsed MBC patients have different risk and prognostic factors for LM. Patients with BCLM have an unfavorable prognosis.

Epidermal keratinocytes are enriched with at least nine connexins that are key regulators of epidermal homeostasis. The role of Cx30.3 in keratinocytes and epidermal health became evident when fourteen autosomal dominant mutations in the Cx30.3-encoding GJB4 gene were linked to a rare and incurable skin disorder called erythrokeratodermia variabilis et progressiva (EKVP). While these variants are linked to EKVP, they remain largely uncharacterized hindering therapeutic options. In this study, we characterize the expression and functional status of three EKVP-linked Cx30.3 mutants (G12D, T85P, and F189Y) in tissue-relevant and differentiation-competent rat epidermal keratinocytes. We found that GFP-tagged Cx30.3 mutants were non-functional likely due to their impaired trafficking and primary entrapment within the endoplasmic reticulum (ER). However, all mutants failed to increase BiP/GRP78 levels suggesting they were not inducing an unfolded protein response. FLAG-tagged Cx30.3 mutants were also trafficking impaired yet occasionally exhibited some capacity to assemble into gap junctions. The pathological impact of these mutants may extend beyond their trafficking deficiencies as keratinocytes expressing FLAG-tagged Cx30.3 mutants exhibited increased propidium iodide uptake in the absence of divalent cations. Attempts to rescue the delivery of trafficking impaired GFP-tagged Cx30.3 mutants into gap junctions by chemical chaperone treatment were ineffective. However, co-expression of wild type Cx30.3 greatly enhanced the assembly of Cx30.3 mutants into gap junctions, although endogenous levels of Cx30.3 do not appear to prevent the skin pathology found in patients harboring these autosomal dominant mutations. In addition, a spectrum of connexin isoforms (Cx26, Cx30, and Cx43) exhibited the differential ability to trans-dominantly rescue the assembly of GFP-tagged Cx30.3 mutants into gap junctions suggesting a broad range of connexins found in keratinocytes may favourably interact with Cx30.3 mutants. We conclude that selective upregulation of compatible wild type connexins in keratinocytes may have potential therapeutic value in rescuing epidermal defects invoked by Cx30.3 EKVP-linked mutants.

Arbuscular mycorrhizal symbiosis (AMS) is an ancient plant-fungus relationship that is widely distributed in terrestrial plants. The formation of symbiotic structures and bidirectional nutrient exchange requires the regulation of numerous genes. However, the landscape of RNAome during plant AMS involving different types of regulatory RNA is poorly understood. In this study, a combinatorial strategy utilizing multiple sequencing approaches was used to decipher the landscape of RNAome in tomato, an emerging AMS model. The annotation of the tomato genome was improved by a multiple-platform sequencing strategy. A total of 3,174 protein-coding genes were upregulated during AMS, 42% of which were alternatively spliced. Comparative-transcriptome analysis revealed that genes from 24 orthogroups were consistently induced by AMS in eight phylogenetically distant angiosperms. Seven additional orthogroups were specifically induced by AMS in all surveyed dicot AMS host plants. However, these orthogroups were absent or not induced in monocots and/or non-AMS hosts, suggesting a continuously evolving AMS-responsive network in addition to a conserved core regulatory module. Additionally, we detected 587 lncRNAs, ten miRNAs, and 146 circRNAs that responded to AMS, which were incorporated to establish a tomato AMS-responsive, competing RNA-responsive endogenous RNA (ceRNA) network. Finally, a tomato symbiotic transcriptome database (TSTD, https://efg.nju.edu.cn/TSTD) was constructed to serve as a resource for deep deciphering of the AMS regulatory network. These results help elucidate the reconfiguration of the tomato RNAome during AMS and suggest a sophisticated and evolving RNA layer responsive network during AMS processes.

Primary porcine tracheal epithelial cells (PTECs) are an appropriate model for studying the molecular mechanism of various porcine respiratory diseases, including swine-origin mycoplasmas, which are isolated from respiratory tract of pigs and mainly found on the mucosal surface surrounding swine trachea. However, the short proliferation ability of primary PTECs greatly limits their lifespan. In this study, primary PTECs were carefully isolated and cultured, and immortal PTECs were constructed by transfecting primary PTECs with the recombinant constructed plasmid pEGFP-hTERT containing human telomerase reverse transcriptase (hTERT). Immortal PTECs (hTERT-PTECs) maintained both the morphological and functional characteristics of primary PTECs, as indicated by the expression of cytokeratin 18, cell-cycle analysis, proliferation assay, Western blotting, telomerase activity assay, karyotype analysis and quantitative RT-PCR. Compared to primary PTECs, hTERT-PTECs had an extended replicative lifespan, higher telomerase activity, and enhanced proliferative activity. In addition, this cell line resulted in a lack of transformed and grown tumors in nude mice, suggesting that it could be safely applied in further studies. Moreover, hTERT-PTECs were vulnerable to all swine-origin mycoplasmas through quantitative analysis as indicated by 50% color changing unit (CCU50) calculation, and no significant differences of adhesion ability between primary and immortal PTECs were observed. For the representative swine mycoplasma Mycoplasma hyopneumoniae (Mhp), except for DNA copies quantitative real-time PCR assay, indirect immunofluorescence assay and Western blotting analysis also depicted that hTERT-PTECs was able to adhere to different Mhp strains of different virulence. In summary, like primary PTECs, hTERT-PTECs could be widely used as an adhesion cell model for swine-origin mycoplasmas and in infection studies of various porcine respiratory pathogens.

Abstract Maternally inherited diabetes and deafness is a rare genetic disease mainly caused by a point mutation in mitochondrial deoxyribonucleic acid. Lipoprotein lipase gene mutations are associated with familial dyslipidemias, which are difficult to manage. We reported for the first time a case that had both maternally inherited diabetes and severe hyperlipidemia caused by lipoprotein lipase gene mutation (C.347(exon3)G>C) that was resistant to fenofibrate and atorvastatin. We were able to manage the patient’s hyperlipidemia with bezafibrate, and her diabetes was well controlled with insulin. In conclusion, genetic testing is helpful in identifying rare and interesting cases when clinicians suspect inheritable diseases. Additionally, when one fibrate drug is ineffective in treating hyperlipidemia, it might be worthwhile trying another fibrate.

Numerous studies have characterized the critical role of circular RNAs (circRNAs) as regulatory factors in the progression of multiple cancers. However, the biological functions of circRNAs and their underlying molecular mechanisms in the progression of uveal melanoma (UM) remain enigmatic. In this study, we identified a novel circRNA, circ_0053943, through re-analysis of UM microarray data and quantitative RT-PCR. Circ_0053943 was found to be upregulated in UM and to promote the proliferation and metastatic ability of UM cells in both in vitro and in vivo settings. Mechanistically, circ_0053943 was observed to bind to the KH1 and KH2 domains of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), thereby enhancing the function of IGF2BP3 by stabilizing its target mRNA. RNA sequencing assays identified epidermal growth factor receptor (EGFR) as a target gene of circ_0053943 and IGF2BP3 at the transcriptional level. Rescue assays demonstrated that circ_0053943 exerts its biological function by stabilizing EGFR mRNA and regulating the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. Collectively, circ_0053943 may promote UM progression by stabilizing EGFR mRNA and activating the MAPK/ERK signaling pathway through the formation of a circ_0053943/IGF2BP3/EGFR RNA-protein ternary complex, thus providing a potential biomarker and therapeutic target for UM. [ABSTRACT FROM AUTHOR]

Abstract Background Time in range (TIR) is advocated as key metric of glycemic control and is reported to be associated with microvascular complications of diabetes. Sudomotor dysfunction is among the earliest detectable diabetic peripheral neuropathy (DPN). We set about to research the relationship between TIR including overnight TIR and sudomotor function detected by SUDOSCAN with the intention of exploring the correlation of TIR including overnight TIR and early DPN in type 1 diabetes (T1D). Methods 95 patients with T1D were enrolled. TIR including nocturnal TIR of 3.9–10.0 mmol/L was evaluated with CGM. SUDOSCAN measured feet electrochemical skin conductance (FESC) and sudomotor dysfunction was defined as average FESC

Summary: Regulatory T cells (Tregs) can inhibit the occurrence of autoimmune diseases and increase the activation threshold of the immune response. Here, we present schemes for the isolation and culture of natural human regulatory T cells (nTregs) and in vitro-induced Tregs (iTregs). Appropriate concentrations of TGF-β, IL-2, retinoic acid (atRA), and rapamycin were used to promote proliferation to meet sample needs in basic research, especially in technologies such as sequencing.For complete details on the use and execution of this protocol, please refer to Lu et al. (2014a) and Gu et al. (2022). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Objective: Myeloma bone disease (MBD) is the most common complication of multiple myeloma (MM). Our previous study showed that the serum levels of C3/C4 in MM patients were significantly positively correlated with the severity of bone disease. However, the mechanism of C3a/C4a in osteoclasts MM patients remains unclear. Methods: The formation and function of osteoclasts were analyzed after adding C3a/C4a in vitro. RNA-seq analysis was used to screen the potential pathways affecting osteoclasts, and the results were verified by Western blot, qRT-PCR, and pathway inhibitors. Results: The osteoclast area per view induced by 1 μg/mL (mean ± SD: 50.828 ± 12.984%) and 10 μg/mL (53.663 ± 12.685%) of C3a was significantly increased compared to the control group (0 μg/mL) (34.635 ± 8.916%) (P < 0.001 and P < 0.001, respectively). The relative mRNA expressions of genes, OSCAR/TRAP/RANKL/cathepsin K, induced by 1 μg/mL (median: 5.041, 3.726, 1.638, and 4.752, respectively) and 10 μg/mL (median: 5.140, 3.702, 2.250, and 5.172, respectively) of C3a was significantly increased compared to the control group (median: 3.137, 2.004, 0.573, and 2.257, respectively) (1 μg/mL P = 0.001, P = 0.003, P < 0.001, and P = 0.008, respectively; 10 μg/mL: P < 0.001, P = 0.019, P < 0.001, and P = 0.002, respectively). The absorption areas of the osteoclast resorption pits per view induced by 1 μg/mL (mean ± SD: 51.464 ± 11.983%) and 10 μg/mL (50.219 ± 12.067%) of C3a was also significantly increased (33.845 ± 8.331%) (P < 0.001 and P < 0.001, respectively) compared to the control. There was no difference between the C4a and control groups. RNA-seq analysis showed that C3a promoted the proliferation of osteoclasts using the phosphoinositide 3-kinase (PI3K) signaling pathway. The relative expressions of PIK3CA/phosphoinositide dependent kinase-1 (PDK1)/serum and glucocorticoid inducible protein kinases (SGK3) genes and PI3K/PDK1/p-SGK3 protein in the C3a group were significantly higher than in the control group. The activation role of C3a in osteoclasts of MM patients was reduced by the SGK inhibitor (EMD638683). Conclusions: C3a activated osteoclasts by regulating the PI3K/PDK1/SGK3 pathways in MM patients, which was reduced using a SGK inhibitor. Overall, our results identified potential therapeutic targets and strategies for MBD patients.

BackgroundProgrammed cell death-1 (PD-1) immune checkpoint inhibitors are not effective in treating all patients with hepatocellular carcinoma (HCC), and regulatory T cells (Tregs) may determine the resistance to anti-PD-1 therapy.MethodsPatients were divided into two groups based on the clinical efficacy of anti-PD-1 therapy. Flow cytometry was used to determine the phenotype of CD4+, CD8+, and Tregs in peripheral blood mononuclear cells (PBMCs). CD4+CD45RA+T cells were sorted to analyze Treg differentiation and function.ResultsNo significant differences were found between resistant and sensitive patients in the percentage of CD4+ T cells and Tregs in PBMCs or the differentiation and function of induced Tregs (iTregs). However, iTregs from resistant patients presented higher monocarboxylate transporter (MCT) expression. Lactate induced more iTregs and improved OXPHOS levels in the resistant group. MCT1 and MCT2 were highly expressed in tumor-infiltrating Tregs, and patients with higher MCT1 expression had worse clinical outcomes. Combinatorial therapy with MCT antibody and anti-PD-1 therapy effectively inhibited tumor growth.ConclusionMCT and its downstream lactate signal in Tregs can confer anti-PD-1 resistance and may be a marker of poor prognosis in HCC.

Abstract Accumulating evidence has suggested that long noncoding RNAs (lncRNAs) exert crucial modulation roles in the biological behaviors of multiple malignancies. Nonetheless, the specific function of lncRNA LINC00284 in papillary thyroid cancer (PTC) remains not fully understood. The objective of this research was to explore the influence of LINC00284 in PTC and elucidate its potential mechanism. The Cancer Genome Atlas (TCGA), gene expression omnibus (GEO) datasets were used to analyze LINC00284 expression differences in thyroid cancer and normal samples, followed by the verification of qRT-PCR in our own PTC and adjacent non-tumor tissues. The impacts of LINC00284 on PTC cell growth were detected in vitro via CCK-8, colony formation, EdU assays, and in vivo via a xenograft tumor model. Bioinformatics analyses and biological experiments were conducted to illuminate the molecular mechanism. We found that LINC00284 expression was remarkably increased in PTC tissues and its overexpression was closely correlated with larger tumor size. In addition, silencing LINC00284 could effectively attenuate PTC cell proliferation, induce apoptosis and G1 arrest in vitro, as well as suppress tumorigenesis in mouse xenografts. Mechanistic investigations showed that LINC00284 acted as a competing endogenous RNA (ceRNA) for miR-3127-5p, thus resulting in the disinhibition of its endogenous target E2F7. In short, our findings indicated that LINC00284–miR-3127-5p–E2F7 axis exerted oncogenic properties in PTC and may offer a new promising target for the diagnosis and therapy of PTC.

Objective: To explore the repair effect of the prepared drug-loaded AM1241 poly(ethylene glycol)–dithiothreitol (PEG-DTT) hydrogel on cranial bone defects in SD rats.Methods: The PEG-DTT hydrogel under borax catalysis was quickly prepared, and the characterization of the material was observed by a scanning electron microscope. The effect of AM1241 on cell activity and bone tissue differentiation was tested. The SD rat model of cranial bone defect was established, and the defect was repaired by injecting the prepared hydrogel into the defect. The defect was divided into four groups, namely, sham group, blank group, PEG-DTT group, and PEG-DTT + AM1241 group. The rats were euthanized, and whole cranial bone was taken out for micro-CT and histological observation.Results: The prepared hydrogel is porous; it is liquid when heated to 80°C and a hydrogel when cooled to 25°C. 5–10 μM AM1241 increased osteoblast activity. A moderate amount of AM1241 can promote osteogenic differentiation. Both the PEG-DTT group and PEG-DTT + AM1241 group showed obvious new bone tissue formation, but the PEG-DTT + AM1241 group had a better effect. In addition, the new bone tissue in the PEG-DTT + AM1241 group was significantly more than that in the other groups.Conclusion: The prepared AM1241-loaded PEG-DTT hydrogel showed a good repair effect on SD rats with cranial bone defects. It can be used as materials for cranial bone repair in SD rats with cranial bone defects, but the repair effect is weaker than that of normal bone. These results provide a theoretical and practical basis for its further clinical application.

Context Rosmarinic acid (RosA), a natural poly-phenolic compound isolated from a variety of Labiatae herbs, has been reported to have a range of biological effects. Objective To investigate the cardioprotective effects of RosA against myocardial ischaemia/reperfusion (I/R) injury. Materials and methods Male C57BL/6J mice were given RosA (100 mg/kg) via intragastric administration. After 1 week of administration, the mice were subjected to 30 min/24 h myocardial I/R injury. The mice were randomly subdivided into 4 groups: Vehicle, RosA, Vehicle + I/R, and RosA + I/R. Infarct size (IS), cardiac function (including EF, FS), histopathology, serum enzyme activities, ROS changes, cis aconitase (ACO) activity, and specific mRNA and protein levels were assessed in vivo. HL-1 cells were pre-treated with or without RosA (50 μM), followed by stimulation with 9 h/6 h of oxygen and glucose deprivation/re-oxygenation (OGD/R). The cells were randomly subdivided into 4 groups: Vehicle, RosA, Vehicle + OGD/R, and RosA + OGD/R. Lactate dehydrogenase (LDH) levels, ACO activity, ROS changes and protein levels were measured in vitro. Results Treatment with RosA reduced the following indicators in vivo (p

Frasier syndrome (FS) is a rare inherited disorder characterized by gonadal dysgenesis and progressive nephropathy, resulting from mutations in the intron 9 splice donor site of the Wilms tumor 1 (WT1) gene. It is associated with male gonadal dysgenesis (female external genitalia with a 46 XY karyotype), and a high risk of gonadoblastoma during adolescence. Patients with FS present early in childhood with proteinuria that progressively worsens with a high likelihood of end-stage renal disease (ESRD). Herein, we report a 15-year-old female (karyotype 46, XY) patient characterized by delayed puberty and steroid-resistant nephrotic syndrome, in whom whole genome sequencing showed a mutation in intron 9 of the WT1 gene, c.1447 + 4 C>T. This is the first case of FS with delayed puberty as the first complaint with no previous renal symptoms. We consider delayed puberty as an important manifestation of FS and summarize the diagnostic process of delayed puberty in the female phenotype. For clinicians, delayed puberty is a common disorder in pediatrics but requires vigilance for some rare causes. Etiological screening and chromosome karyotype analysis are important for the early diagnosis of FS in patients with delayed puberty.

Streptococcus suis serotype 2 (S. suis 2) is an important swine pathogen and also an emerging zoonotic agent. HtpsA has been reported as an immunogenic cell surface protein on the bacterium. In the present study, we constructed an isogenic mutant strain of htpsA, namely ΔhtpsA, to study its role in the development and virulence of S. suis 2. Our results showed that the mutant strain lost its typical encapsulated structure with decreased concentrations of sialic acid. Furthermore, the survival rate in whole blood, the anti-phagocytosis by RAW264.7 murine macrophage, and the adherence ability to HEp-2 cells were all significantly affected in the ΔhtpsA. In addition, the deletion of htpsA sharply attenuated the virulence of S. suis 2 in an infection model of mouse. RNA-seq analysis revealed that 126 genes were differentially expressed between the ΔhtpsA and the wild-type strains, including 28 upregulated and 98 downregulated genes. Among the downregulated genes, many were involved in carbohydrate metabolism and synthesis of virulence-associated factors. Taken together, htpsA was demonstrated to play a role in the morphological development and pathogenesis of the highly virulent S. suis 2 05ZYH33 strain.

Retinoblastoma (RB) is the most common childhood malignant intraocular tumor. The clinical efficacy of vincristine (VCR) in the treatment of RB is severely limited by drug resistance. Here, we found that CD24, a GPI‐anchored protein, was overexpressed in human RB tissues and RB cell lines, and was associated with the sensitivity of RB cells in response to VCR therapy. We demonstrated that CD24 plays a critical role in impairing RB sensitivity to VCR via regulating autophagy. Mechanistically, CD24 recruits PTEN to the lipid raft domain and regulates the PTEN/AKT/mTORC1 pathway to activate autophagy. Lipid raft localization was essential for CD24 recruitment function. Collectively, our findings revealed a novel role of CD24 in regulating RB sensitivity to VCR and showed that CD24 is a potential target for improving chemotherapeutic sensitivity and RB patient outcomes.

Retinoblastoma (RB) is the most common intraocular malignancy of childhood caused by inactivation of the Rb genes. The prognosis of RB is better with an earlier diagnosis. Many diagnostic approaches and appropriate clinical treatments have been developed to improve clinical outcomes. However, limitations exist when utilizing current methods. Recently, many studies have identified identify new RB biomarkers which can be used in diagnosis, as prognostic indicators and may contribute to understanding the pathogenesis of RB and help determine specific treatment strategies. This review focuses on recent advances in the discovery of RB biomarkers and discusses their clinical utility and challenges from areas such as epigenetics, proteomics and radiogenomics.

Context Traditionally, Clematis tangutica Korsh. (Ranunculaceae) is used as a Tibetan herb for treating indigestion and blood stasis in China. Recently, a flavonoid glycoside, apigenin-7-O-β-d-(6″-p-coumaroyl)-glucopyranoside (APG), was isolated from the whole plant of C. tangutica. Objective To investigate the cardioprotective effects of APG against myocardial ischaemia/reperfusion injury (MI/RI) and the possible mechanism. Materials and methods Animals were subjected to 30 min/3 h MI/RI model. At the end of reperfusion, infarct size (IS), histopathology, serum levels CK-MB, LDH, TNF-α, IL-6 and MPO activities were detected. Phospho-IκB-α, ICAM-1 and NF-κB were assessed in vivo. Neonatal rat cardiomyocytes were pre-treated with or without APG, followed by stimulation with 8 h/2 h oxygen and glucose deprived/reoxygenation (OGD/R) model. Cell viability, LDH and cardiomyocyte apoptosis were assessed. The expression levels of phospho-IκB-α and NF-κB were measured in vitro. Results Treatment with APG significantly reduced the following indicators in vivo (p

Chimeric antigen receptor T (CAR-T) cells show good efficacy in the treatment of relapsed and refractory B-cell tumors, such as acute B-cell leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). The main toxicities of CAR-T include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, cytopenia, and severe infection. It is still very difficult for CAR-T to kill tumor cells to the maximum extent and avoid damaging normal organs. Here, we report a case of DLBCL with persistent grade 4 thrombocytopenia and severe platelet transfusion dependence treated with CD19 CAR-T cells. We used sirolimus to inhibit the sustained activation of CAR-T cells and restore normal bone marrow hematopoiesis and peripheral blood cells. Moreover, sirolimus treatment did not affect the short-term efficacy of CAR-T cells, and DLBCL was in complete remission at the end of follow-up. In conclusion, sirolimus can represent a new strategy for the management of CAR-T cell therapy-related toxicity, including but not limited to hematotoxicity. However, further controlled clinical studies are required to confirm these findings.

Plants have evolved sophisticated systems to cope with the environmental stresses, with the heat shock factor (HSF) family proteins composing an integral part of the transcriptional regulation system. Understanding the evolutionary history and functional diversity of HSFs will facilitate improving tolerance of crops to adverse environmental conditions. In this study, genome-wide analysis of Secale cereale identified 31 HSF genes. The total number of HSF genes in S. cereale is larger than that in barley and the three subgenomes of wheat, suggesting it is a valuable resource for mining functional HSFs. Chromosome analysis revealed an uneven distribution of HSF genes among the 7 S. cereale chromosomes, with no HSF gene was detected on chromosome 4. Further interspecies synteny analysis revealed that chromosome reorganization during species-speciation may lead to the escape of HSF genes from the S. cereale chromosome 4. Phylogenetic analysis revealed that S. cereale experienced more HSF gene duplications than barley and the three wheat subgenomes. Expression analysis demonstrated that S. cereale HSF genes showed diverse expression patterns across plant developmental stages and upon drought and freezing treatment, suggesting functional diversity of the gene family. Notably, we detected distinct expression patterns for a recently duplicated HSF gene pair, indicating functional divergence may have occurred between the two genes. The study presents the genome organization, evolutionary features and expression patterns of the S. cereale HSF genes. These results provide new insights into the evolution of HSF genes in Triticeae and may serve as a resource for Triticeae molecular breeding.

Liver fibrosis is a progression stage of chronic liver disease, while current therapies cannot cure or attune cirrhosis effectively. Human amniotic mesenchymal stromal cell (hAMSC) presented immunoregulatory and tissue repairability of multiple illnesses. Regulatory T cells (Treg) had been proved to be functional in reducing immune cell activity. We showed that co-infusion of hAMSC and Treg prevented mild liver fibrosis comparing with hAMSC or Treg alone group. In vitro study indicated that the addition of Treg or the supernatant of Treg improved the hepatocyte growth factor (HGF) secreting and cell differentiation ability of hAMSC. Reduction of TGF-β significantly decreased the HGF secreting and differentiation of hAMSC. Multiple signal neutralizers were added to the culture to understand further the mechanism, which showed that 1-MT, the suppressor of Indoleamine 2,3-dioxygenase (IDO), was involved in the effect of TGF-β in regulating hAMSC. Depletion of TGF-β or IDO signaling successfully abolished the effect of Treg in improving hAMSC’s function both in vitro and vivo. Finally, our result indicated that Treg improved the function of hAMSC by regulating the TGF-β-IDO signaling and co-infusion of hAMSC and Treg provided a promising approach for treating liver cirrhosis.

Treatment of ocular infection involves pharmacotherapy with steroids and antibiotic drops, such as moxifloxacin hydrochloride (MFH) and dexamethasone sodium phosphate (DSP). To characterize the pharmacokinetics of these two compounds, we performed and validated a liquid chromatography-mass spectrometry (LC-MS/MS) method to quantify them in rabbit ocular tissues and plasma. We used protein precipitation to extract the compounds. The analyte and internal standard (IS) were separated using a Shim-pack Scepter C18 column. The mobile phase was composed of 0.1% formic acid water (A) and methanol (B). MFH and DSP were detected using positive ion electrostatic ionization (ESI) in multiple reaction monitoring mode (MRM). The calibration curves for both compounds showed good linearity over concentrations ranging from 0.5 to 200 ng/mL in rabbit ocular tissues and plasma. The lower limit of quantification for both MFH and DSP was 0.5 ng/mL. We validated this method for selectivity, linearity (r2 > 0.99), precision, accuracy, matrix effects, and stability. Thus, we used this method to assess the pharmacokinetic (PK) characteristics of MFH and DSP in rabbit ocular tissues and plasma after single doses. Our results indicate that this method can be used for the simultaneous analysis of moxifloxacin hydrochloride and dexamethasone sodium phosphate in clinical samples.