Search

Background: SZ-685C, an anthracycline compound derived from the mangrove endophytic fungus Halorosellinia sp. (No. 1403) collected from the South China Sea, has shown strong anticancer activities. Non-functioning pituitary adenomas (NFPAs) are a type of tumor that can be challenging to manage clinically and have a significant unmet medical need. Our research has found that SZ-685C showed an inhibitory effect on the viability, migration ability, and proliferation ability of a human non-functioning pituitary tumor-derived folliculostellate (PDFS) cell line. Methods: SZ-685C was prepared and purified from the mangrove endophytic fungus No. 1403. PDFS cells were exposed to SZ-685C, and the effect of SZ-685C on PDFS cells was evaluated. RNA sequencing was used to analyze the miRNA expression profile in PDFS cells of the control group and SZ-685C-treated group. Quantitative polymerase chain reaction (qPCR) was performed to verify the expression of selected miR-340-3p. The effects of SZ-685C on PDFS cells after overexpression of miR-340-3p were evaluated. Dual-luciferase reporter assays showed PPP1CB is a direct target of miR-340-3p. Finally, the action pathway of the selected miR-340-3p was predicted and evaluated through bioinformatics analysis. Results: SZ-685C reduced cell viability in PDFS cells, accompanied by inhibition of migration ability and proliferation ability. The IC50 value for 24 h is 9.144 ± 0.991 μM, and for 48 h is 4.635 ± 0.551 μM. SZ-685C increased the protein levels of Beclin 1, the ratio of LC3-II to LC3-I, and LAMP-1, and down-regulated p62. MiRNA sequencing and further validation showed that miR-340-3p significantly decreased in PDFS cells treated with SZ-685C. After overexpression of miR-340-3p, the inhibition of viability, migration ability, proliferation ability, and autophagy-promoting effect of SZ-685C on PDFS cells were weakened. SZ-685C caused a decrease in PPP1CB expression and activation of the ERK pathway in PDFS cells, and this trend was reversed after overexpression of miR-340-3p. Conclusions: SZ-685C downregulates the expression of miR-340-3p in PDFS cells, thereby reducing the expression of PPP1CB and activating the ERK pathway to promote autophagic cell death, leading to inhibition of PDFS cell growth.

Background: Allergic rhinitis (AR) has a high burden of disease in the Asia-Pacific region (APAC). Although guidelines provide recommendations regarding the diagnosis and treatment of AR, it is increasingly being recognised that there are gaps in their implementation. Patient-centred care involves accounting for the specific needs and desires of patients as well as including the patient in the decision-making process, and this may provide a means to reduce these gaps and consequently the burden of AR. Methods: A group of 11 experts in immunology and otorhinolaryngology from APAC provided information regarding their practices and experiences in the management of AR through an online survey. The group then discussed the barriers and solutions for the implementation of patient-centred care across the patient journey in a face-to-face meeting. Results: Key barriers to the implementation of patient-centred care for AR in APAC included a lack of patient awareness of the condition and treatment options, low adherence to treatments, financial constraints for patients, and time constraints for physicians. The solutions proposed include improving the knowledge of the patients about their conditions, the use of shared decision-making, the consideration of patient characteristics when choosing treatments, and the use of outcome measures to aid the optimisation of patient care. We provide specific recommendations for clinical practice. Conclusion: A greater focus on patient-centred approaches has the potential to improve the management of AR in APAC. More emphasis should be placed on each patient's specific health needs and desired outcomes.

Abstract The bioactivity of interferon-γ (IFN-γ) in cancer cells in the tumor microenvironment (TME) is not well understood in the current immunotherapy era. We found that IFN-γ has an immunosuppressive effect on colorectal cancer (CRC) cells. The tumor volume in immunocompetent mice was significantly increased after subcutaneous implantation of murine CRC cells followed by IFN-γ stimulation, and RNA sequencing showed high expression of B7 homologous protein 4 (B7H4) in these tumors. B7H4 promotes CRC cell growth by inhibiting the release of granzyme B (GzmB) from CD8+ T cells and accelerating apoptosis in CD8+ T cells. Furthermore, interferon regulatory factor 1 (IRF1), which binds to the B7H4 promoter, is positively associated with IFN-γ stimulation-induced expression of B7H4. The clinical outcome of patients with CRC was negatively related to the high expression of B7H4 in cancer cells or low expression of CD8 in the microenvironment. Therefore, B7H4 is a biomarker of poor prognosis in CRC patients, and interference with the IFN-γ/IRF1/B7H4 axis might be a novel immunotherapeutic method to restore the cytotoxic killing of CRC cells.

Abstract Background Pneumocystis pneumonia (PCP) is a life-threatening opportunistic fungal infection with a high mortality rate in immunocompromised patients, ranging from 20 to 80%. However, current understanding of the variation in host immune response against Pneumocystis across different timepoints is limited. Methods In this study, we conducted a time-resolved single-cell RNA sequencing analysis of CD45+ cells sorted from lung tissues of mice infected with Pneumocystis. The dynamically changes of the number, transcriptome and interaction of multiply immune cell subsets in the process of Pneumocystis pneumonia were identified according to bioinformatic analysis. Then, the accumulation of Trem2hi interstitial macrophages after Pneumocystis infection was verified by flow cytometry and immunofluorescence. We also investigate the role of Trem2 in resolving the Pneumocystis infection by depletion of Trem2 in mouse models. Results Our results characterized the CD45+ cell composition of lung in mice infected with Pneumocystis from 0 to 5 weeks, which revealed a dramatic reconstitution of myeloid compartments and an emergence of PCP-associated macrophage (PAM) following Pneumocystis infection. PAM was marked by the high expression of Trem2. We also predicted that PAMs were differentiated from Ly6C+ monocytes and interacted with effector CD4+ T cell subsets via multiple ligand and receptor pairs. Furthermore, we determine the surface markers of PAMs and validated the presence and expansion of Trem2hi interstitial macrophages in PCP by flow cytometry. PAMs secreted abundant pro-inflammation cytokines, including IL-6, TNF-α, GM-CSF, and IP-10. Moreover, PAMs inhibited the proliferation of T cells, and depletion of Trem2 in mouse lead to reduced fungal burden and decreased lung injury in PCP. Conclusion Our study delineated the dynamic transcriptional changes in immune cells and suggests a role for PAMs in PCP, providing a framework for further investigation into PCP’s cellular and molecular basis, which could provide a resource for further discovery of novel therapeutic targets.

Hypoxia has become a common phenomenon in aquatic environments. Golden pompano (Trachinotus blochii) are sensitive to fluctuations in dissolved oxygen concentration and are seriously affected by hypoxic stress. When facing hypoxia in aquaculture areas, it may be effective to alleviate the adverse effects of low oxygen by increasing dissolved oxygen through physical and chemical means. However, it is not known whether different reoxygenation rates have different physiological consequences. In this study, we utilized RNA-seq and miRNA-seq to investigate the effects of various hypoxia and reoxygenation treatments: normoxia, hypoxia, rapid reoxygenation (RRG; dissolved oxygen [DO] recovery within 10 mins), and gradual reoxygenation (GRG; DO recovery within 3 h). Under hypoxic conditions, the miR-130b-5p∼IDH3 pair was involved in the regulation of the TCA cycle and activation of HIF-1α expression in response to insufficient oxygen levels. Additionally, in RRG, under the regulation of the miR-132–5p∼PGAM, miR-8485∼LIPA, and miR-212–5p∼GAPDHS pairs, the energy supply came to increase relative to hypoxia. In GRG, the miR-130b-5p∼IDH3 pair regulated metabolism, which returned to the normal level. These findings provide new data for clarifying the metabolic regulatory pathways of golden pompano during hypoxia and reoxygenation processes.

Urban street space is a significant component of urban public spaces and an important aspect of people’s perceptions of a city. Jinan Old City exemplifies the balance between the supply of and demand for green spaces in urban streets. The sense of comfort and the demand level of street spaces are measured via the space demand index. Open platform data, such as those from Baidu Maps and Amap, are evaluated using methods including ArcGIS network analysis and Segnet semantic segmentation. The results obtained from such evaluations indicate that, in terms of the green space supply, the overall level for Shangxin Street in Jinan is not high. Only 24% of the selected sites have an adequate green space supply. The level on Wenhua West Road is higher than that on Shangxin Street. The block on the western side of Shangxin Street has the highest green space demand, with a decreasing trend from west to east. There are several higher selection points in the middle section of Shangxin Street. The demand is lowest in the middle of Wenhua East Road. Shangxin Street’s demand is higher than that of Wenhua West Road. The supply and demand are highly matched on Wenhua West Road and poorly matched on Shangxin Street, with 44.12% of the area in the “low supply, high demand” quadrant. This study proposes targeted optimization strategies based on supply and demand, thereby providing research ideas and methods for urban renewal.

IntroductionSystematic evaluation of long-term outcomes in survivors of H1N1 is still lacking. This study aimed to characterize long-term outcomes of severe H1N1-induced pneumonia and acute respiratory distress syndrome (ARDS).MethodThis was a single-center, prospective, cohort study. Survivors were followed up for four times after discharge from intensive care unit (ICU) by lung high-resolution computed tomography (HRCT), pulmonary function assessment, 6-minute walk test (6MWT), and SF-36 instrument.ResultA total of 60 survivors of H1N1-induced pneumonia and ARDS were followed up for four times. The carbon monoxide at single breath (DLCO) of predicted values and the 6MWT results didn’t continue improving after 3 months. Health-related quality of life didn’t change during the 12 months after ICU discharge. Reticulation or interlobular septal thickening on HRCT did not begin to improve significantly until the 12-month follow-up. The DLCO of predicted values showed negative correlation with the severity degree of primary disease and reticulation or interlobular septal thickening, and a positive correlation with physical functioning. The DLCO of predicted values and reticulation or interlobular septal thickening both correlated with the highest tidal volume during mechanical ventilation. Levels of fibrogenic cytokines had a positive correlation with reticulation or interlobular septal thickening.ConclusionThe improvements in pulmonary function and exercise capacity, imaging, and health-related quality of life had different time phase and impact on each other during 12 months of follow-up. Long-term outcomes of pulmonary fibrosis might be related to the lung injury and excessive lung fibroproliferation at the early stage during ICU admission.

The objective of the study is to investigate the mechanism by which summer pruning enhances the growth of pepper plants, as indicated by growth and fruit appearance indicators, photosynthetic rate and gas exchange parameters, rapid light response and induction kinetics curves and the related chlorophyll fluorescence parameters. The results indicated that the leaf growth rate, the individual pepper fruit weight, and the fruit longitudinal and cross diameters of the pruned group were significantly higher than those of the control. The stomatal conductance (Gs), intercellular CO2 concentration (Ci) and transpiration rate (Tr) of the pruned group were significantly higher than those of the control. The initial slope of the rapid light response curve, which represents light energy utilisation efficiency (α), the maximum electron transfer rate (Jmax) and saturated light intensity (PARsat) were all higher in the summer pruning group than in the control group. The F0 of the pruned group decreased by 16.83%, Fv/F0 increased by 23.69%, PIabs increased by 58.33%, and DIo/RC decreased by 22.09% compared to the control group. In summary, summer pruning significantly improves the leaf growth rate and fruit appearance quality of pepper, effectively promotes the photosynthesis of functional leaves, and reduces the degree of stress under adverse environmental conditions.

BackgroundSilicosis shows an increasing trend with the development of new industries. However, the potential biomarkers for predicting the disease severity are lacking. A novel inflammatory marker, the systemic immune-inflammation Index (SII), has not been studied in silicosis.MethodsIn this retrospective study, we used data from a big database platform of a tertiary general hospital in Beijing, which was established based on the electronic medical records of the hospital. The clinical data of adult patients diagnosed with silicosis at the Department of Occupational Medicine and Toxicology from 2013 to 2022 were collected. The data extracted from the database were in de-identified form. Only patients with a first diagnosis of silicosis and without conditions that might affect the parameters of routine blood tests were included in the analysis. Analyses were performed to assess the relationship between SII and the advanced stage of silicosis.ResultsA total of 246 participants were included in the study. Most of the patients were exposed to silica particles during excavation and digging (n = 149, 60.6%). SII level was significantly higher in patients with advanced stages of silicosis. A multivariate logistic regression analysis revealed that a higher SII level was associated with the advanced stage of silicosis [odds ratio (OR) = 1.002; 95% confidence interval (CI): 1.000–1.003, p

Abstract Objectives To examine the characteristics of blood lymphocyte subsets in dermatomyositis-interstitial lung disease (DM-ILD) inflicted patients with positive anti-melanoma differentiation-associated gene 5 (anti-MDA5), as well as its prognosis value in this set of patients. Methods Data were retrospectively collected from 253 DM-ILD patients from three hospitals in China between January 2016 to January 2021. Patients were grouped into anti-MDA5 antibody positive group (MDA5+ DM-ILD) and anti-MDA5 antibody negative group (MDA5− DM-ILD) based on myositis-specific autoantibody test results. Demographic characteristics, lymphocyte subsets patterns and other clinical features were compared between the two groups. The association of lymphocyte subsets with 180-day mortality was investigated using survival analysis in MDA5+ DM-ILD. Results Out of 253 eligible patients with DM-ILD, 59 patients were anti-MDA5+ and 194 were anti-MDA5−. Peripheral blood lymphocyte count, CD3+ count, percentage of CD3+, CD3+CD4+ count, and CD3+CD8+ count was lower in MDA5+ DM-ILD than in MDA5− DM-ILD− (all P

Abstract Polymer dielectrics with excellent thermal resistance and superior energy storage behaviour are extensively demanded with the increasing development of film capacitors applied in hostile environments. In this study, novel diamine with sulfonyl‐containing side chain was designed and synthesised. The corresponding polyimide (PI) dielectrics derived from the sulfonyl‐containing diamine were prepared, so were the polyimides possessing the same backbone but without side chains. Consequently, superior thermal resistance of glass transition temperature ranged from 162–208°C was obtained. Moreover, the polyimides presented permittivity of 3.34–5.89 at 1 kHz, Weibull breakdown strength of 377–538 MV/m and discharged energy density of 3.82–5.85 J/cm3. In particular, sulfonyl‐containing polyimide of SPI‐2 with flexible backbone and sulfonyl side chain indicates the highest discharged energy density and charge‐discharge efficiency simultaneously. The introduction of the strong polar sulfonyl group in the side chain enhances dielectric and energy storage properties effectively. In addition, it is found that the dipolar moment density (μ/Vvdw) calculated from molecular simulation is closely correlated to permittivity measured from experiments. The combined method of molecular simulation and experiments would offer an effective approach to assist in molecular design of high‐performance polymer dielectrics.

Abstract Introduction Psittacosis can cause severe community-acquired pneumonia (CAP). The clinical manifestations of psittacosis range from subclinical to fulminant psittacosis with multi-organ failure. It is essential to summarize the clinical characteristic of patients with severe psittacosis accompanied by acute hypoxic respiratory failure (AHRF). Methods This retrospective study included patients with severe psittacosis caused CAP accompanied by AHRF from 19 tertiary hospitals of China. We recorded the clinical data, antimicrobial therapy, respiratory support, complications, and outcomes. Chlamydia psittaci was detected on the basis of metagenomic next-generation sequencing performed on bronchoalveolar lavage fluid samples. Patient outcomes were compared between the treatment methods. Results This study included 45 patients with severe CAP and AHRF caused by psittacosis from April 2018 to May 2021. The highest incidence of these infections was between September and April. There was a history of poultry contact in 64.4% of the patients. The median PaO2/FiO2 of the patients was 119.8 (interquartile range, 73.2 to 183.6) mmHg. Four of 45 patients (8.9%) died in the ICU, and the median ICU duration was 12 days (interquartile range, 8 to 21) days. There were no significant differences between patients treated with fluoroquinolone initially and continued after the diagnosis, fluoroquinolone initially followed by tetracycline, and fluoroquinolone combined with tetracycline. Conclusion Psittacosis caused severe CAP seems not rare, especially in the patients with the history of exposure to poultry or birds. Empirical treatment that covers atypical pathogens may benefit such patients, which fluoroquinolones might be considered as an alternative.

Abstract Vehicle emission is a major source of atmospheric secondary organic aerosols (SOA). Driving condition is a critical influencing factor for vehicular SOA production, but few studies have revealed the dependence on rapid-changing real-world driving conditions. Here, a fast-response oxidation flow reactor system is developed and deployed to quantify the SOA formation potential under transient driving conditions. Results show that the SOA production factor varies by orders of magnitude, e.g., 20–1500 mg kg-fuel−1 and 12–155 mg kg-fuel−1 for China V and China VI vehicles, respectively. High speed, acceleration, and deceleration are found to considerably promote SOA production due to higher organic gaseous emissions caused by unburned fuel emission or incomplete combustion. In addition, China VI vehicles significantly reduce SOA formation potential, yield, and acceleration and deceleration peaks. Our study provides experimental insight and parameterization into vehicular SOA formation under transient driving conditions, which would benefit high time-resolved SOA simulations in the urban atmosphere.

Introduction: Historical-cultural landscapes and urbanscapes integrate regional culture, collective memory, urban patterns, living habits, and other related historical and spatial information, and are important places for expressing the values of urban space. This study analyzes cultural landscapes and urbanscapes from the perspective of spatial values, taking the Baihuazhou historic and cultural district in Jinan as an example to analyze the spatial identification of public cultural space. The significance of this research lies in examining the urban regeneration of public cultural space using multi-scale geospatial data from both an objective and subjective perspective. This methdology is based on a large body of previous literature in relation to cultural heritage, and draws on a comprehensive understanding of the field.Methods: This study applies spatial syntax, visual graph, and survey analyses, focusing on urban spatial patterns, spatial culture, and spatial memory as heritage values.Results: The analysis results reveal that historic districts generally do not have good accessibility, predominantly because of the disorganized texture of the buildings and absence of spatial consistency.Discussion: There should be improved dynamic spatial identification and accessibility in older urban environments and enhancement of local spatial identification memory by increasing sightline accessibility. Based on consideration of values, corresponding suggestions are made from the three perspectives of urban space, cultural landscapes, and local collective memories to provide a reference for the protection of the Baihuazhou historic district and promote the preservation and development of similar heritage spaces.

CDGSH iron sulfur domain 2 can inhibit ferroptosis, which has been associated with cerebral ischemia/reperfusion, in individuals with head and neck cancer. Therefore, CDGSH iron sulfur domain 2 may be implicated in cerebral ischemia/reperfusion injury. To validate this hypothesis in the present study, we established mouse models of occlusion of the middle cerebral artery and HT22 cell models of oxygen-glucose deprivation and reoxygenation to mimic cerebral ischemia/reperfusion injury in vivo and in vitro, respectively. We found remarkably decreased CDGSH iron sulfur domain 2 expression in the mouse brain tissue and HT22 cells. When we used adeno-associated virus and plasmid to up-regulate CDGSH iron sulfur domain 2 expression in the brain tissue and HT22 cell models separately, mouse neurological dysfunction was greatly improved; the cerebral infarct volume was reduced; the survival rate of HT22 cells was increased; HT22 cell injury was alleviated; the expression of ferroptosis-related glutathione peroxidase 4, cystine-glutamate antiporter, and glutathione was increased; the levels of malondialdehyde, iron ions, and the expression of transferrin receptor 1 were decreased; and the expression of nuclear-factor E2-related factor 2/heme oxygenase 1 was increased. Inhibition of CDGSH iron sulfur domain 2 upregulation via the nuclear-factor E2-related factor 2 inhibitor ML385 in oxygen-glucose deprived and reoxygenated HT22 cells blocked the neuroprotective effects of CDGSH iron sulfur domain 2 up-regulation and the activation of the nuclear-factor E2-related factor 2/heme oxygenase 1 pathway. Our data indicate that the up-regulation of CDGSH iron sulfur domain 2 can attenuate cerebral ischemia/reperfusion injury, thus providing theoretical support from the perspectives of cytology and experimental zoology for the use of this protein as a therapeutic target in patients with cerebral ischemia/reperfusion injury.

Abstract Background Critically ill patients in intensive care units (ICUs) are at high risk of venous thromboembolism (VTE). This study aimed to explore the prophylaxis effect under a guideline-based thromboprophylaxis protocol among critically ill patients in a respiratory ICU. Methods For this single-center prospective cohort study, we followed the thromboprophylaxis protocol, which was drawn up based on relevant guidelines and Chinese experts’ advice. Clinical data were entered into an electronic case report form and analyzed. Multivariate logistic regression was conducted to explore independent risk factors of VTE event under this protocol. Results From August 1, 2014, to December 31, 2020, 884 patients underwent thromboprophylaxis according to this protocol; 10.5% of them received mechanical prophylaxis, 43.8% received pharmacological prophylaxis, and 45.7% received pharmacological combined with mechanical prophylaxis. The proportion of VTE events was 14.3% for patients who received the thromboprophylaxis protocol, of which 0.1% had pulmonary thromboembolism (PTE), 2.0% had proximal deep vein thrombosis (DVT), and 12.1% had isolated distal DVT. There was no significant difference between different thromboprophylaxis measures. Cirrhosis (OR 5.789, 95% CI [1.402, 23.894], P = 0.015), acute asthma exacerbation (OR 39.999, 95% CI [4.704, 340.083], P = 0.001), and extracorporeal membrane oxygenation treatment (OR 22.237, 95%CI [4.824, 102.502], P

Background: Long intergenic non-protein coding RNA 1426 (LINC01426) is up-regulated in glioma and functions as a tumor promoter. However, the role of LINC01426 in glioma required further exploration. Therefore, this article mainly studied the role and possible mechanism of LINC01426 in glioma. Methods: The area under the receiver operating characteristic curve was used to determine the diagnostic value of LINC01426. The effect of LINC01426 on tumor growth was analyzed by tumorigenesis assay and immunohistochemical analysis. Bioinformatics analysis, dual-luciferase assay, RNA pull-down, Pearson test, and real-time quantitative PCR (RT-qPCR) were applied to verify the relationship between target genes. The expressions and effects of LINC01426, miR-661 and MDM2 proto-oncogene (Mdm2) in glioma were examined by bioinformatics analysis combined with molecular and functional experiments (RT-qRCR, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide, clone formation, BrdU, flow cytometry). The expressions of proliferation and apoptosis-related proteins were determined by Western blot. Results: LINC01426, which was high-expressed in glioma and was related to poor prognosis, could be used as a diagnostic marker for glioma. SiLINC01426 inhibited the malignant phenotype of glioma cells in vitro and attenuated tumor growth and PCNA expression in vivo, while the effects of LINC01426 were the opposite. LINC01426 targeted and inversely correlated with miR-661, which was low-expressed in glioma. MiR-661 inhibitor evidently overturned the effect of siLINC01426 on biological functions, proliferation, and apoptosis-related proteins of glioma cells. Mdm2 bound to miR-661. Moreover, siMdm2 reversed the effects of miR-661 inhibitor on the biological characteristics and Mdm2/p53/p21 expression of glioma cells. Conclusion: LINC01426 aggravated the malignant progression of glioma through miR-661/Mdm2 axis.

In agricultural production, temperature and moisture are important factors affecting grain yield and quality. Although moderate drought at the grain-filling stage can effectively alleviate the damage caused by high temperature, the specific regulatory mechanism driving the effect of moderate drought at the high temperature on starch synthesis is still unclear. To explore the effects and mechanisms of high temperature and moderate drought on rice starch synthesis at the grain-filling stage, the activities of enzymes and expression levels of the genes involved in starch synthesis under four different treatments involving high temperature and/or water stress (CK, HT, WS, and HT+WS) were investigated in this study. The starch synthesis of a japonica inbred rice was measured under the four treatments during the grain filling. The results show that the effects of high temperature and moderate drought on grain filling mainly occur in the inferior grains of rice. Through the regulation of enzymes involved in starch synthesis and the expression levels of their main genes, the synthesis of rice starch can be affected. Therefore, the high temperature and moderate drought were antagonistic, and moderate drought can alleviate the damage to grain quality at a high temperature by improving the starch synthesis of inferior grains in japonica rice. This study provides a basis for stress-resistance cultivation and breeding strategies of rice with high temperature tolerance.

Stroke is one of the leading causes of death and long-term disability worldwide. More than 80 % of strokes are ischemic, caused by an occlusion of cerebral arteries. Without question, restoration of blood supply as soon as possible is the first therapeutic strategy. Nonetheless paradoxically, reperfusion can further aggravate the injury through a series of reactions known as cerebral ischemia-reperfusion injury (CIRI). Mitochondria play a vital role in promoting nerve survival and neurological function recovery and mitochondrial dysfunction is considered one of the characteristics of CIRI. Neurons often die due to oxidative stress and an imbalance in energy metabolism following CIRI, and there is a strong association with mitochondrial dysfunction. Altered mitochondrial dynamics is the first reaction of mitochondrial stress. Mitochondrial dynamics refers to the maintenance of the integrity, distribution, and size of mitochondria as well as their ability to resist external stimuli through a continuous cycle of mitochondrial fission and fusion. Therefore, improving mitochondrial dynamics is a vital means of treating CIRI. This review discusses the relationship between mitochondria and CIRI and emphasizes improving mitochondrial dynamics as a potential therapeutic approach to improve the prognosis of CIRI.

Abstract Background Repair of peripheral nerve defect presents a considerable challenge for reconstructive surgeons. The aim of this study is to develop a brain-derived neurotrophic factor (BDNF) from poly(D,L-lactide-co-glycolide) (PLGA) microspheres for the treatment of the peripheral nerve defect. Method BDNF microspheres were prepared by using an oil-in-water emulsification-solvent evaporation method. The morphology, particle size, encapsulation efficiency, drug loading and sustained release performance of microspheres was observed and calculated. Adipose mesenchymal stem cells (ADSCs) were isolated and expanded. ADSCs were divided into four groups: control, BDNF, blank microsphere and BDNF microsphere groups. Cell count kit-8 (CCK-8) assays were used to assess cell proliferation. Cell migration was determined by Transwell assays. Twenty-eight male Sprague–Dawley rats underwent transection damage model on the right sciatic nerve. The wet weight ratio of the gastrocnemius muscle was calculated by comparing the weight of the gastrocnemius muscle from the operated side to that of the normal side. Neuroelectrophysiological testing was performed to assess nerve function recovery. Nerve regeneration was evaluated by histological analysis and immunohistochemical staining. Results The microspheres were spherical and had uniform size (46.38 ± 1.00 μm), high encapsulation efficiency and high loading capacity. In vitro release studies showed that BDNF-loaded microspheres had good sustained release characteristics. The duration of BDNF release was extended to more than 50 days. BDNF or BDNF microsphere promote the proliferation and migration of ADSCs than control group (P

Nonfunctioning pituitary adenoma (NFPA) is one of the major subtypes of pituitary adenomas (PA) and its primary treatment is surgical resection. However, normal surgery fails to remove lesions completely and there remains in lack of frontline treatment, so the development of new drugs for NFPA is no doubt urgent. Oridonin (ORI) has been reported to have antitumor effects on a variety of tumors, but whether it could exhibit the same effect on NFPA requires to be further investigated. The effects of ORI on pituitary‐derived folliculostellate cell line (PDFS) cell viability, colony formation, proliferation ability, migration, and invasion were examined by Cell Counting Kit‐8, colony formation assay, 5‑Ethynyl‑2'‑deoxyuridine proliferation assay, wound‐healing assay, and Transwell assay. The differentially expressed genes in the control and ORI‐treated groups were screened by transcriptome sequencing analysis and analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment. Cell cycle analysis was performed to detect changes in cell cycle. Annexin V‐fluorescein isothiocyanate/propidium iodide staining was performed to detect apoptosis in ORI‐treated cells. Western blot assay was performed to detect Bax, Bcl‐2, and cleaved Caspase‐3 protein expression. ORI inhibited PDFS cell viability and significantly suppressed cell proliferation, migration, and invasion. GO and KEGG results showed that ORI was associated with signaling pathways such as cell cycle and apoptosis in PDFS cells. In addition, ORI blocked cells in G2/M phase and induced apoptosis in PDFS cells. ORI can trigger cell cycle disruption and apoptosis collaboratively in PDFS cells, making it a promising and effective agent for NFPA therapy. [ABSTRACT FROM AUTHOR]

Abstract Background The incidence of acute pancreatitis (AP) is increasing over years, which brings enormous economy and health burden. However, the aetiologies of AP and underlying mechanisms are still unclear. Here, we performed a two‐sample Mendelian randomization (MR) analysis to investigate the associations between all reported possible risk factors and AP using publicly available genome‐wide association study summary statistics. Methods A series of quality control steps were taken in our analysis to select eligible instrumental single nucleotide polymorphisms which were strongly associated with exposures. To make the conclusions more robust and reliable, we utilized several analytical methods (inverse‐variance weighting, MR‐PRESSO method, weighted median, MR‐Egger regression) that are based on different assumptions of two‐sample MR analysis. The MR‐Egger intercept test, radial regression and leave‐one‐out sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on each exposure. A two‐step MR method was applied to explore mediators in significant associations. Results Genetic predisposition to cholelithiasis (effect estimate: 17.30, 95% CI: 12.25–22.36, p = 1.95 E‐11), body mass index (0.32, 95% CI: 0.13–0.51, p

Summary: MXene, 2D material, can be synthesized as single flake with 1 nm thickness by using phase change material, polymer and graphene oxide. Meanwhile, the MXene and its composite derivative materials have been applied widely in electro-to-thermal conversion, photo-to-thermal conversion, thermal energy storage, and 3D printing ink aspects. Furthermore, the forward-looking utilization of the MXene nanomaterials in hydrogen energy storage, radio frequency field application, CO2 capture and remediation of environmental pollution, is explored. This article reveals that the efficiencies of the photo-to-thermal and electro-to-thermal energy conversions with the MXene nanomaterials could reach about 80–90%. In parallel, it is demonstrated that the MXene printed ink has the excellent rheological property and high viscosity and stability of liquid, which contribute to arranging the multi-dimensional architectures with functional materials and controlling the flow rate of the MXene ink in the range of 0.03–0.15 mL/min for speedily printing and various printing structures.

Abstract Background Oligoasthenospermia is one of the main causes of male infertility. Researchers usually use chemical drugs to directly damage germ cells to prepare oligoasthenospermia models, which disregards the adhesion and migration between spermatogenic cells and Sertoli cells. TAp73 is a critical regulator of the adhesin of germ cell; thus, we sought to explore a novel oligoasthenospermia model based on TAp73 gene suppression. Methods Mice in the Pifithrin‐α group were injected intraperitoneally with 2.5 mg/kg Pifithrin‐α (TAp73 inhibitor) daily for 30 consecutive days. Reproductive hormone levels and epididymal sperm quality, as well as the network morphology of Sertoli cells were tested. Results Sperm density, motility, and the relative protein and mRNA expression of TAp73 and Nectin 2 were obviously decreased in the Pifithrin‐α group compared with the normal control group. No significant distinction was observed in the relative mRNA and protein expression of ZO‐1. Furthermore, the tight junctions (TJs) and apical ectoplasmic specialization (ES) were destroyed in the Pifithrin‐α group. Conclusion The above results indicate that we successfully established a new oligoasthenospermia mouse model. This study provides a foundation for further exploration of the roles of TAp73 genes during spermatogenesis and provides new research objects for further oligospermia research and future drug discovery.

Abstract Background Hypoxemia frequently occurs during bronchoscopy. High-flow nasal cannula (HFNC) oxygen therapy may be a feasible alternative to prevent the deterioration of gas exchange during bronchoscopy. With the convenience of clinical use in mind, we modified an HFNC using a single cannula. This clinical trial was designed to test the hypothesis that a modified HFNC would decrease the proportion of patients with a single moment of peripheral arterial oxygen saturation (SpO2) 60 ml (OR, 1.034; 95% CI, 1.002–1.067, p = 0.036) were independent risk factors for hypoxemia during bronchoscopy in the modified HFNC group. Conclusions A modified HFNC could decrease the proportion of patients with a single moment of SpO2