The value of CT radiomics combined with deep transfer learning in predicting the nature of gallbladder polypoid lesions.

BACKGROUND: Computed tomography (CT) radiomics combined with deep transfer learning was used to identify cholesterol and adenomatous gallbladder polyps that have not been well evaluated before surgery. PURPOSE: To investigate the potential of various machine learning models, incorporating radiomics and deep transfer learning, in predicting the nature of cholesterol and adenomatous gallbladder polyps. MATERIAL AND METHODS: A retrospective analysis was conducted on clinical and imaging data from 100 patients with cholesterol or adenomatous polyps confirmed by surgery and pathology at our hospital between September 2015 and February 2023. Preoperative contrast-enhanced CT radiomics combined with deep learning features were utilized, and t-tests and least absolute shrinkage and selection operator (LASSO) cross-validation were employed for feature selection. Subsequently, 11 machine learning algorithms were utilized to construct prediction models, and the area under the ROC curve (AUC), accuracy, and F1 measure were used to assess model performance, which was validated in a validation group. RESULTS: The Logistic algorithm demonstrated the most effective prediction in identifying polyp properties based on 10 radiomics combined with deep learning features, achieving the highest AUC (0.85 in the validation group, 95% confidence interval = 0.68-1.0). In addition, the accuracy (0.83 in the validation group) and F1 measure (0.76 in the validation group) also indicated strong performance. CONCLUSION: The machine learning radiomics combined with deep learning model based on enhanced CT proves valuable in predicting the characteristics of cholesterol and adenomatous gallbladder polyps. This approach provides a more reliable basis for preoperative diagnosis and treatment of these conditions.

Interleukin-4 protects retinal ganglion cells and promotes axon regeneration.

BACKGROUND: The preservation of retinal ganglion cells (RGCs) and the facilitation of axon regeneration are crucial considerations in the management of various vision-threatening disorders. Therefore, we investigate the efficacy of interleukin-4 (IL-4), a potential therapeutic agent, in promoting neuroprotection and axon regeneration of retinal ganglion cells (RGCs) as identified through whole transcriptome sequencing in an in vitro axon growth model. METHODS: A low concentration of staurosporine (STS) was employed to induce in vitro axon growth. Whole transcriptome sequencing was utilized to identify key target factors involved in the molecular mechanism underlying axon growth. The efficacy of recombinant IL-4 protein on promoting RGC axon growth was validated through in vitro experiments. The protective effect of recombinant IL-4 protein on somas of RGCs was assessed using RBPMS-specific immunofluorescent staining in mouse models with optic nerve crush (ONC) and N-methyl-D-aspartic acid (NMDA) injury. The protective effect on RGC axons was evaluated by anterograde labeling of cholera toxin subunit B (CTB), while the promotion of RGC axon regeneration was assessed through both anterograde labeling of CTB and immunofluorescent staining for growth associated protein-43 (GAP43). RESULTS: Whole-transcriptome sequencing of staurosporine-treated 661 W cells revealed a significant upregulation in intracellular IL-4 transcription levels during the process of axon regeneration. In vitro experiments demonstrated that recombinant IL-4 protein effectively stimulated axon outgrowth. Subsequent immunostaining with RBPMS revealed a significantly higher survival rate of RGCs in the rIL-4 group compared to the vehicle group in both NMDA and ONC injury models. Axonal tracing with CTB confirmed that recombinant IL-4 protein preserved long-distance projection of RGC axons, and there was a notably higher number of surviving axons in the rIL-4 group compared to the vehicle group following NMDA-induced injury. Moreover, intravitreal delivery of recombinant IL-4 protein substantially facilitated RGC axon regeneration after ONC injury. CONCLUSION: The recombinant IL-4 protein exhibits the potential to enhance the survival rate of RGCs, protect RGC axons against NMDA-induced injury, and facilitate axon regeneration following ONC. This study provides an experimental foundation for further investigation and development of therapeutic agents aimed at protecting the optic nerve and promoting axon regeneration.

Enhancing the Efficiency and Stability of Tin-Lead Perovskite Solar Cells via Sodium Hydroxide Dedoping of PEDOT:PSS.

Tin-lead (Sn-Pb) perovskite solar cells (PSCs) have gained interest as candidates for the bottom cell of all-perovskite tandem solar cells due to their broad absorption of the solar spectrum. A notable challenge arises from the prevalent use of the hole transport layer, PEDOT:PSS, known for its inherently high doping level. This high doping level can lead to interfacial recombination, imposing a significant limitation on efficiency. Herein, NaOH is used to dedope PEDOT:PSS, with the aim of enhancing the efficiency of Sn-Pb PSCs. Secondary ion mass spectrometer profiles indicate that sodium ions diffuse into the perovskite layer, improving its crystallinity and enlarging its grains. Comprehensive evaluations, including photoluminescence and nanosecond transient absorption spectroscopy, confirm that dedoping significantly reduces interfacial recombination, resulting in an open-circuit voltage as high as 0.90 V. Additionally, dedoping PEDOT:PSS leads to increased shunt resistance and high fill factor up to 0.81. As a result of these improvements, the power conversion efficiency is enhanced from 19.7% to 22.6%. Utilizing NaOH to dedope PEDOT:PSS also transitions its nature from acidic to basic, enhancing stability and exhibiting less than a 7% power conversion efficiency loss after 1176 h of storage in N2 atmosphere.

Generation of SARS-CoV-2 spike receptor binding domain mutants and functional screening for immune evaders using a novel lentivirus-based system.

The emergence of rapid and continuous mutations of severe acute respiratory syndrome 2 (SARS-CoV-2) spike glycoprotein that increased with the Omicron variant points out the necessity to anticipate such mutations for conceiving specific and adaptable therapies to avoid another pandemic. The crucial target for the antibody treatment and vaccine design is the receptor binding domain (RBD) of the SARS-CoV-2 spike. It is also the site where the virus has shown its high ability to mutate and consequently escape immune response. We developed a robust and simple method for generating a large number of functional SARS-CoV-2 spike RBD mutants by error-prone PCR and a novel nonreplicative lentivirus-based system. We prepared anti-RBD wild type (WT) polyclonal antibodies and used them to screen and select for mutant libraries that escape inhibition of virion entry into recipient cells expressing human angiotensin-converting enzyme 2 and transmembrane serine protease 2. We isolated, cloned, and sequenced six mutants totally bearing nine mutation sites. Eight mutations were found in successive WT variants, including Omicron and other recombinants, whereas one is novel. These results, together with the detailed functional analyses of two mutants provided the proof of concept for our approach.

Decreased hepatic enzymes reflect the decreased vitamin B6 levels in Parkinson's disease patients.

The study aims to investigate the vitamin B6 levels in Parkinson's disease (PD) patients and their association with liver enzymes and evaluate how much dysregulation is associated with levodopa dose. Furthermore, to evaluate the effect of Opicapone, a catechol-o-methyl-transferase inhibitor, on vitamin B6 levels by monitoring the AST and ALT levels in patients treated with Levodopa-Carbidopa Intestinal Gel Infusion (LCIG). For these aims, serum vitamin B6 levels were measured (PD, n = 72 and controls, n = 31). The vitamin B6 level was compared with the total levodopa dose, clinical parameters, and blood homocysteine, albumin, and hemoglobin levels in PD patients. Correlations between vitamin B6 levels and AST and ALT levels, as well as the ratio ALT/AST, were analyzed. Changes in the AST and ALT levels and ALT/AST were analyzed in the patients treated with LCIG before and after the therapy (n = 24) and in the patients treated with LCIG + Opicapone before and after Opicapone treatment (n = 12). We found vitamin B6 levels were significantly lower in PD patients. Total levodopa dose and albumin levels were independently associated with vitamin B6 levels. Decreased vitamin B6 levels appeared as lower AST and ALT levels and ALT/AS. Treatment with LCIG decreased the AST and ALT levels and ALT/AST. Adjunctive therapy with Opicapone to LCIG ameliorated the decreased ALT and ALT/AST. We conclude that the ALT and ALT/AST can be useful parameters for monitoring vitamin B6 levels and Opicapone can ameliorate the dysregulated vitamin B6 in PD patients.

Lysophagy protects against propagation of α-synuclein aggregation through ruptured lysosomal vesicles.

The neuron-to-neuron propagation of misfolded α-synuclein (αSyn) aggregates is thought to be key to the pathogenesis of synucleinopathies. Recent studies have shown that extracellular αSyn aggregates taken up by the endosomal-lysosomal system can rupture the lysosomal vesicular membrane; however, it remains unclear whether lysosomal rupture leads to the transmission of αSyn aggregation. Here, we applied cell-based αSyn propagation models to show that ruptured lysosomes are the pathway through which exogenous αSyn aggregates transmit aggregation, and furthermore, this process was prevented by lysophagy, i.e., selective autophagy of damaged lysosomes. αSyn aggregates accumulated predominantly in lysosomes, causing their rupture, and seeded the aggregation of endogenous αSyn, initially around damaged lysosomes. Exogenous αSyn aggregates induced the accumulation of LC3 on lysosomes. This LC3 accumulation was not observed in cells in which a key regulator of autophagy, RB1CC1/FIP200, was knocked out and was confirmed as lysophagy by transmission electron microscopy. Importantly, RB1CC1/FIP200-deficient cells treated with αSyn aggregates had increased numbers of ruptured lysosomes and enhanced propagation of αSyn aggregation. Furthermore, various types of lysosomal damage induced using lysosomotropic reagents, depletion of lysosomal enzymes, or more toxic species of αSyn fibrils also exacerbated the propagation of αSyn aggregation, and impaired lysophagy and lysosomal membrane damage synergistically enhanced propagation. These results indicate that lysophagy prevents exogenous αSyn aggregates from escaping the endosomal-lysosomal system and transmitting aggregation to endogenous cytosolic αSyn via ruptured lysosomal vesicles. Our findings suggest that the progression and severity of synucleinopathies are associated with damage to lysosomal membranes and impaired lysophagy.

Involvement of Mitochondria in Parkinson's Disease.

Mitochondrial dysregulation, such as mitochondrial complex I deficiency, increased oxidative stress, perturbation of mitochondrial dynamics and mitophagy, has long been implicated in the pathogenesis of PD. Initiating from the observation that mitochondrial toxins cause PD-like symptoms and mitochondrial DNA mutations are associated with increased risk of PD, many mutated genes linked to familial forms of PD, including PRKN, PINK1, DJ-1 and SNCA, have also been found to affect the mitochondrial features. Recent research has uncovered a much more complex involvement of mitochondria in PD. Disruption of mitochondrial quality control coupled with abnormal secretion of mitochondrial contents to dispose damaged organelles may play a role in the pathogenesis of PD. Furthermore, due to its bacterial ancestry, circulating mitochondrial DNAs can function as damage-associated molecular patterns eliciting inflammatory response. In this review, we summarize and discuss the connection between mitochondrial dysfunction and PD, highlighting the molecular triggers of the disease process, the intra- and extracellular roles of mitochondria in PD as well as the therapeutic potential of mitochondrial transplantation.

An improved method for the synthesis and formation mechanism of M2B10H14 based on the reactions of B10H14 with MNH2BH3 (M = Na, K).

An efficient method for the synthesis of M2B10H14 (M = Na and K) has been developed. The two possible formation mechanisms of the B10H142- anion are proposed, in which the NH2BH3- anion acts as a proton abstractor and a hydride donor. Furthermore, the B10H13- and B10H15- intermediates were detected.

Value of ultrasound guided biopsy combined with Xpert Mycobacterium tuberculosis/resistance to rifampin assay in the diagnosis of chest wall tuberculosis.

BACKGROUND: The thoracic wall lesions, particularly chest wall tuberculosis, and chest wall tumors and other pyogenic wall and actinomycetes infections, almost always present as a diagnostic challenge. AIM: To explore the value of ultrasound-guided biopsy combined with the Xpert Mycobacterium tuberculosis/resistance to rifampin (MTB/RIF) assay to diagnose chest wall tuberculosis. METHODS: We performed a retrospective study of patients with chest wall lesions from March 2018 to March 2021. All patients received the ultrasound-guided biopsy for pathology examination, acid-fast Bacillus staining, mycobacterial culture, and Xpert MTB/RIF analysis. The sensitivity, specificity, and area under the curve (AUC) were calculated for these diagnostic tests, either individually or combined. Rifampicin resistance results were compared between the mycobacterial culture and the Xpert MTB/RIF assay. RESULTS: In 31 patients with the chest wall lesion biopsy, 22 patients were diagnosed with chest wall tuberculosis. Of them, 3, 6, and 21 patients tested positive for mycobacterial culture, acid-fast stain, and Xpert MTB/RIF assay, respectively. The rifampicin resistance results of the 3 culture-positive patients were consistent with their Xpert MTB/RIF assay results. When considering the sensitivity, specificity, and AUC value, the Xpert MTB/RIF assay (95.5%, 88.9%, and 0.92, respectively) was a better choice than the acid-fast Bacillus stain (27.3%, 100.0%, and 0.64, respectively) and mycobacterial culture (13.6%, 100.0%, 0.57, respectively). No complications were reported during the procedure. CONCLUSION: Ultrasound guided biopsy combined with Xpert MTB/RIF has high value in the diagnosis of chest wall tuberculosis, and can also detect rifampicin resistance.

Lower geriatric nutritional risk index is associated with a higher risk of all-cause mortality in patients with chronic obstructive pulmonary disease: a cohort study from the National Health and Nutrition Examination Survey 2013-2018.

OBJECT: Malnutrition negatively affects patients with chronic obstructive pulmonary disease (COPD). This study aimed to explore the potential association between malnutrition, as defined by the Geriatric Nutritional Risk Index (GNRI), and all-cause mortality in patients with COPD using the National Health and Nutrition Examination Survey (NHANES). METHOD: The data of 579 adults with COPD during NHANES 2013-2018 were analysed. Each patient was assigned to one of the two groups according to GNRI values: normal nutritional status (GNRI>98) and malnutrition status (GNRI≤98). Survival curves and Cox regressions were applied to evaluate the association between nutritional status and mortality. RESULTS: Overall, the mean age was 63.4±0.5 years, and 53.9% of the patients were women. The prevalence of malnutrition was 6.6%, and the Kaplan-Meier curves for all-cause mortality according to nutritional status showed that malnutrition was associated with a higher incidence of all-cause mortality. The Cox regression analysis found that in the unadjusted model, the HR was 2.30 (95% CI 1.24 to 4.27, p=0.01). In the fully adjusted model, the adjusted HR was 2.47 (95% CI 1.36 to 4.5, p=0.003). Furthermore, subgroup analysis revealed that the risk of death due to malnutrition increased more than threefold in the low education and cancer subgroups. CONCLUSION: A low GNRI was an independent risk factor for all-cause mortality in patients with COPD.

Promotion of axon regeneration and protection on injured retinal ganglion cells by rCXCL2.

BACKGROUND: In addition to rescuing injured retinal ganglion cells (RGCs) by stimulating the intrinsic growth ability of damaged RGCs in various retinal/optic neuropathies, increasing evidence has shown that the external microenvironmental factors also play a crucial role in restoring the survival of RGCs by promoting the regrowth of RGC axons, especially inflammatory factors. In this study, we aimed to screen out the underlying inflammatory factor involved in the signaling of staurosporine (STS)-induced axon regeneration and verify its role in the protection of RGCs and the promotion of axon regrowth. METHODS: We performed transcriptome RNA sequencing for STS induction models in vitro and analyzed the differentially expressed genes. After targeting the key gene, we verified the role of the candidate factor in RGC protection and promotion of axon regeneration in vivo with two RGC-injured animal models (optic nerve crush, ONC; retinal N-methyl-D-aspartate, NMDA damage) by using cholera toxin subunit B anterograde axon tracing and specific immunostaining of RGCs. RESULTS: We found that a series of inflammatory genes expressed upregulated in the signaling of STS-induced axon regrowth and we targeted the candidate CXCL2 gene since the level of the chemokine CXCL2 gene elevated significantly among the top upregulated genes. We further demonstrated that intravitreal injection of rCXCL2 robustly promoted axon regeneration and significantly improved RGC survival in ONC-injured mice in vivo. However, different from its role in ONC model, the intravitreal injection of rCXCL2 was able to simply protect RGCs against NMDA-induced excitotoxicity in mouse retina and maintain the long-distance projection of RGC axons, yet failed to promote significant axon regeneration. CONCLUSIONS: We provide the first in vivo evidence that CXCL2, as an inflammatory factor, is a key regulator in the axon regeneration and neuroprotection of RGCs. Our comparative study may facilitate deciphering the exact molecular mechanisms of RGC axon regeneration and developing high-potency targeted drugs.

Phosphatidylinositol-3,4,5-trisphosphate interacts with alpha-synuclein and initiates its aggregation and formation of Parkinson's disease-related fibril polymorphism.

Lipid interaction with α-synuclein (αSyn) has been long implicated in the pathogenesis of Parkinson's disease (PD). However, it has not been fully determined which lipids are involved in the initiation of αSyn aggregation in PD. Here exploiting genetic understanding associating the loss-of-function mutation in Synaptojanin 1 (SYNJ1), a phosphoinositide phosphatase, with familial PD and analysis of postmortem PD brains, we identified a novel lipid molecule involved in the toxic conversion of αSyn and its relation to PD. We first established a SYNJ1 knockout cell model and found SYNJ1 depletion increases the accumulation of pathological αSyn. Lipidomic analysis revealed SYNJ1 depletion elevates the level of its substrate phosphatidylinositol-3,4,5-trisphosphate (PIP3). We then employed Caenorhabditis elegans model to examine the effect of SYNJ1 defect on the neurotoxicity of αSyn. Mutations in SYNJ1 accelerated the accumulation of αSyn aggregation and induced locomotory defects in the nematodes. These results indicate that functional loss of SYNJ1 promotes the pathological aggregation of αSyn via the dysregulation of its substrate PIP3, leading to the aggravation of αSyn-mediated neurodegeneration. Treatment of cultured cell line and primary neurons with PIP3 itself or with PIP3 phosphatase inhibitor resulted in intracellular formation of αSyn inclusions. Indeed, in vitro protein-lipid overlay assay validated that phosphoinositides, especially PIP3, strongly interact with αSyn. Furthermore, the aggregation assay revealed that PIP3 not only accelerates the fibrillation of αSyn, but also induces the formation of fibrils sharing conformational and biochemical characteristics similar to the fibrils amplified from the brains of PD patients. Notably, the immunohistochemical and lipidomic analyses on postmortem brain of patients with sporadic PD showed increased PIP3 level and its colocalization with αSyn. Taken together, PIP3 dysregulation promotes the pathological aggregation of αSyn and increases the risk of developing PD, and PIP3 represents a potent target for intervention in PD.

The specific signs of lung ultrasound to diagnose pulmonary hemorrhage of the newborns: Evidence from a multicenter retrospective case-control study.

Objectives: Pulmonary hemorrhage (PH) is one kind of critical lung diseases in newborn infants, which is the most difficult one to be diagnosed by ultrasound. This study was to investigate the specific ultrasonic signs of PH in order to better diagnose neonatal PH by using lung ultrasound (LUS). Methods: A total 168 newborn infants were enrolled in this study, which included PH, pneumonia, meconium aspiration syndrome, and newborns without lung diseases, there were 42 cases in each group. In a quiet state, infants were placed in the supine, lateral or prone position for the examination. Each lung was divided into the anterior, lateral and posterior regions, then each region of both lungs was scanned with the probe perpendicular to the ribs or parallel to the Intercostal spaces. Results: The major results showed that: (1) the common LUS manifestation of PH includes lung consolidation, air bronchograms, fluid bronchograms, pleural effusion, shred signs, pleural line abnormality and B-lines, while fibrin deposition sign is a rare sign of PH. (2) Co-existing of lung consolidation with fluid bronchograms and pleural effusion is the specific sign of PH with a sensitivity of 81.0%, specificity of 98.4% and the positive predictive value (PPV) was 94.4%. (3) Fibrin deposition sign is an uncommon specific LUS sign of PH with a sensitivity 28.6%, specificity of 100% and the PPV was 100%. (4) Nine patients (21.4%) were diagnosed with PH based on ultrasound findings before oronasal bleeding. (5) The survival rate of infants with PH was 100% in this study. Conclusion: LUS is helpful for the early diagnosis of neonatal PH and may therefore improve the prognosis. The lung consolidation with fluid bronchograms and pleural effusion as well as fibrin deposition sign are specific to diagnose PH by using LUS.

Oral vs. parenteral antibiotic therapy in adult patients with community-acquired pneumonia: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Antibiotic therapy is widely used for patients with community-acquired pneumonia (CAP), and yet whether the efficacy of antibiotics differs based on the treatment mode remains unclear. This study aimed to summarize the evidence regarding the efficacy and safety of oral vs. parenteral administration of antibiotic therapy for the treatment of patients with CAP. METHODS: The databases of PubMed, EmBase, and the Cochrane Central Register of Controlled Trials were systematically searched for eligible randomized controlled trials (RCTs) from inception until 11 December 2021. The effectiveness of oral vs. parenteral administration of antibiotic therapy was estimated using a random-effects model. Additional sensitivity, subgroup, and publication bias analyses were performed. RESULTS: Of 912 identified articles, 12 RCTs involving 2158 patients with CAP were included in our pooled analysis. This mostly included trials with low certainty and some concerns regarding risk of bias, including lack of allocation concealment and blinding of participants and personnel. Overall, oral antibiotic therapy did not affect the incidence of clinical success at the end of treatment (relative risk [RR], 1.01; 95% confidence interval [CI], 0.98-1.05; P = 0.417), clinical success at follow-up (RR, 1.02; 95% CI, 0.98-1.06; P = 0.301), or adverse events (RR, 0.87; 95% CI, 0.56-1.35; P = 0.527). Moreover, oral antibiotic therapy had a beneficial effect on the risk of all-cause mortality (RR, 0.58; 95% CI, 0.35-0.96; P = 0.034). CONCLUSIONS: Oral administration of antibiotics is associated with a reduced risk of all-cause mortality compared with parenteral therapy based on RCTs with low to moderate quality. This finding should be verified in further large-scale RCTs.

Mesenchymal Stem Cells Promote Intestinal Mucosal Repair by Positively Regulating the Nrf2/Keap1/ARE Signaling Pathway in Acute Experimental Colitis.

BACKGROUND/AIMS: Mesenchymal stem cells (MSCs) are a type of adult pluripotent stem cell that has anti-inflammatory and immunomodulatory effects, and whose conditioned medium (CM) has also been found to be effective. We used MSC and CM enemas to investigate their ameliorative effects in a mouse model of colitis. METHODS: We employed MSCs, CM, and MSCs + ML385 (an inhibitor of Nrf2) in dextran sodium sulfate (DSS)-induced colitis. Mice were sacrificed on day 8, and the effects of MSC or CM treatment on the levels of inflammation and oxidative stress in colonic epithelial cells were evaluated by histological analyses. RESULTS: MSCs inhibited inflammatory cell infiltration and proinflammatory cytokine expression in the colon. In addition, MSCs reduced extracellular matrix deposition and maintained the mechanical barrier and permeability of colonic epithelial cells. Mechanistically, MSCs activated Nrf2, which then increased HO-1 and NQO-1 levels and downregulated the expression of Keap1 to suppress reactive oxygen species production and MDA generation, accompanied by increases in components of the enzymatic antioxidant system, including SOD, CAT, GSH-Px, and T-AOC. However, after administering an Nrf2 inhibitor (ML385) to block the Nrf2/Keap1/ARE pathway, we failed to observe protective effects of MSCs in mice with colitis. CM alone also produced some of the therapeutic benefits of MSCs but was not as effective as MSCs. CONCLUSIONS: Our data confirmed that MSCs and CM can effectively improve intestinal mucosal repair in experimental colitis and that MSCs can improve this condition by activating the Nrf2/Keap1/ARE pathway.

Conditioned medium of mesenchymal stem cells pretreated with H2O2 promotes intestinal mucosal repair in acute experimental colitis.

Mesenchymal stem cells (MSCs) are a new therapeutic strategy for inflammatory bowel disease (IBD), and their efficacy has been widely recognized. However, there are still some challenges in cell therapy, including stable cell passage, laboratory conditions for cell culture, high-cost burden, and poor transplantation. The conditioned medium (CM) of MSCs is considered be an excellent alternative to cell transplantation, but the paracrine group in MSC-CM is limited in variety and low in concentration, which cannot meet the therapeutic needs of injured tissues and needs to be optimized. Pretreatment with low concentration of hydrogen peroxide (H2O2) can not only protect cells from oxidative damage, but also play a role similar to growth factors and regulate the physiological function of stem cells, to obtain an improved conditioned medium. To determine the optimal protocol for pretreatment of MSCs with H2O2, and to study the efficacy and potential mechanism of MSC-CM pretreated with H2O2 on Dextran Sulfate Sodium (DSS)-induced acute experimental colitis. MSCs were exposed to different concentrations of H2O2, and the optimal H2O2 pretreatment conditions were determined by evaluating their critical cell functional properties. H2O2-pretreated MSC-CM was transplanted into experimental mouse colitis by enema at 2, 4, and 6 days in modeling, and the changes of colonic tissue structure, the levels of inflammation and oxidative stress, the molecular changes of Nrf2/Keap1/ARE axis, and the related indicators of apoptosis in colonic epithelial cells were observed in each group. In vitro, Pretreated MSCs with 25 µM H2O2 significantly enhanced cell proliferation, migration, and survival, but had no effect on apoptosis. In vivo, MSC-CM treatment decreased apoptosis and extracellular matrix deposition, and maintained the mechanical barrier and permeability of colonic epithelial cells in experimental mouse colitis. Mechanistically, H2O2-pretreated MSC-CM against reactive oxygen species (ROS) production and MDA generation, accompanied by increases in components of the enzymatic antioxidant system includes SOD, CAT, GSH-PX, and T-AOC, which is through the up-regulation of the Nrf2, HO-1, and NQO-1 antioxidant genes. Our data confirmed that 25 µM H2O2 pretreated MSC-CM treatment could effectively improve intestinal mucosal repair in experimental colitis, which may be achieved by activating Nrf2/Keap1/ARE pathway.

Management of stent-related tracheoesophageal fistula in complex post-tuberculosis tracheobronchial stenosis: A case report.

Background: The covered self-expandable metallic stents (SEMS) have been used to manage benign tracheobronchial stenosis, especially the complex post-tuberculosis (TB) tracheobronchial stenosis (PTTS) with cartilage destruction or malacia. This procedure could lead to stent-related tracheoesophageal fistula (TEF). Case presentation: A 21-year-old woman, who had one covered Y-shaped SEMS inserted to manage complex PTTS 2 years ago, presented with dyspnea and frequent coughing on drinking water. The bronchoscopy confirmed extensive granulation tissue hyperplasia and a TEF on the upper edge of the covered SEMS. The covered SEMS was removed in three steps, and another fully covered Y-shape SEMS (Microtech Co., Ltd., Nanjing, China) was inserted to restore patency in the tracheobronchial tree and occlude the TEF orifice. Recombinant bovine basic fibroblast growth factor (rbFGF) (6,000 IU/time) was sprayed into and around the fistula through the V-System single-use cannula via the flexible bronchoscope every other week. The patient showed sustained clinical and radiographic improvement, and the TEF healed. Conclusion: We presented a three-step bronchoscopic approach to managing a stent-related TEF in a patient with complex PTTS. Subsequently, regular bronchoscopic debridement of granulation tissue developing on the upper edge of SEMS is necessary to maintain the stent patency and reduce the risk of recurrent stent-related TEF. A fully covered SEMS associated with the local administration of rbFGF seems to offer an alternative simplified one-stage procedure for the temporary management of TEF combined with complex PTTS in non-surgical candidates.

Considerations for the Use of Photobiomodulation in the Treatment of Retinal Diseases.

Photobiomodulation (PBM) refers to the beneficial effect produced from low-energy light irradiation on target cells or tissues. Increasing evidence in the literature suggests that PBM plays a positive role in the treatment of retinal diseases. However, there is great variation in the light sources and illumination parameters used in different studies, resulting in significantly different conclusions regarding PBM's therapeutic effects. In addition, the mechanism by which PBM improves retinal function has not been fully elucidated. In this study, we conducted a narrative review of the published literature on PBM for treating retinal diseases and summarized the key illumination parameters used in PBM. Furthermore, we explored the potential molecular mechanisms of PBM at the retinal cellular level with the goal of providing evidence for the improved utilization of PBM in the treatment of retinal diseases.

Yeast U6 snRNA made by RNA polymerase II is less stable but functional.

U6 small nuclear (sn)RNA is the shortest and most conserved snRNA in the spliceosome and forms a substantial portion of its active site. Unlike the other four spliceosomal snRNAs, which are synthesized by RNA polymerase (RNAP) II, U6 is made by RNAP III. To determine if some aspect of U6 function is incompatible with synthesis by RNAP II, we created a U6 snRNA gene with RNAP II promoter and terminator sequences. This "U6-II" gene is functional as the sole source of U6 snRNA in yeast, but its transcript is much less stable than U6 snRNA made by RNAP III. Addition of the U4 snRNA Sm protein binding site to U6-II increased its stability and led to formation of U6-II•Sm complexes. We conclude that synthesis of U6 snRNA by RNAP III is not required for its function and that U6 snRNPs containing the Sm complex can form in vivo. The ability to synthesize U6 snRNA with RNAP II relaxes sequence restraints imposed by intragenic RNAP III promoter and terminator elements and allows facile control of U6 levels via regulators of RNAP II transcription.