Association of the m6 A reader IGF2BP3 with tumor progression and brain-specific metastasis in breast cancer.

BACKGROUND: This study aimed to determine the role of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an N6 -methyladinosine reader, in the progression and distant metastasis of breast cancer. METHODS: IGF2BP3 expression was assessed in 152 pairs of breast cancer and adjacent normal tissue (ANT) by real-time quantitative polymerase chain reaction and in 561 cases of breast cancer and 163 cases of ANT by immunohistochemistry. Survival curves were estimated using the Kaplan-Meier method and then compared statistically using the log-rank test. The prognostic role of IGF2BP3 was determined by Cox regression analysis. RESULTS: Analysis of public gene data sets revealed that IGF2PB3 predicted distant metastasis in breast cancer and was highly correlated with brain metastasis. In the clinical retrospective cohort, the positive rate of IGF2BP3 increased gradually with breast cancer progression. Positive IGF2BP3 expression was related to poor distant metastasis-free survival (DMFS, p = .030) and Cox regression analysis identified IGF2BP3 as an independent risk factor for DMFS (hazard ratio, 1.876; 95% confidence interval, 1.128-3.159; p = .019). Positive IGF2BP3 expression was markedly related to breast cancer brain metastasis (p = .011) but not to lung and bone metastasis. Moreover, patients with IGF2BP3-positive brain metastasis had lower survival than patients with IGF2BP3-negative brain metastasis (p = .041). Gene expression profiling results indicated that high IGF2BP3 expression was associated with the PD-1 checkpoint pathway, HER2-HER3 signaling, and epithelial-mesenchymal transition. CONCLUSIONS: IGF2BP3 may serve as a novel predictive biomarker and a potential therapeutic target for breast cancer brain metastasis, which warrants further investigation. PLAIN LANGUAGE SUMMARY: As an m6 A reader, IGF2BP3 is dysregulated and implicated in various cancers but its role in breast cancer has not been fully clarified. In this study, we found that IGF2BP3 was upregulated in breast cancer and IGF2BP3 expression increased gradually during breast cancer progression. IGF2BP3 expression exerted no effect on the overall survival and breast cancer-specific survival of breast cancer patients; however, IGF2BP3-positive patients were more likely to develop distant metastasis than IGF2BP3-negative patients. In addition, IGF2BP3 was associated with brain-specific metastasis in breast cancer patients. These findings warrant further investigation because they provide a rationale for novel predictive or therapeutic approaches.

Assessment of Human Exposure to Traditional and Novel Organophosphate Esters via Multiple Personal Matrices.

Herein, 16 traditional and 13 novel organophosphate esters (OPEs) in skin wipes, personal PM2.5, sputum, and nails (fingernails and toenails) and 7 OPE metabolites in urine synchronously obtained from 64 college students were analyzed. Similar compositional profiles of the OPEs were found in skin wipes and nails and in personal PM2.5 and induced sputum. Significant correlations were observed between the concentrations of high-lipophilicity low-volatility OPEs in skin wipes and nails and between the concentrations of high-volatility low-lipophilicity OPEs in personal PM2.5 and sputum. These results imply that OPEs in fingernails and toenails may mainly come from external sources rather than internal exposure, and human nails and sputum can be used as indicators of human exposure to OPEs. A comparison between the daily exposure doses of the OPEs in personal PM2.5 and sputum shows that more volatile compounds may have higher inhalation bioavailability, which should be considered to improve the accuracy of inhalation exposure assessments. According to comprehensive external and internal exposure assessment, dermal absorption may be a more dominant pathway than inhalation, and skin wipes may be the best representative environmental matrix of human exposure to OPEs.

Trajectory model to analyse the effect of multi-metal exposures on sperm parameters and sex hormones of the MARHCS cohort in China.

BACKGROUND: At present, several cross-sectional studies have found that exposure to metal/metalloid elements is closely associated with male reproduction. However, the long-term effects of metal exposure on male reproduction have not been explored. METHODS: In 2013, 796 volunteers were recruited, followed by first and second follow-ups in 2014 and 2015. Urine, semen, and blood samples were collected at each stage to examine urinary metal/metalloid levels, sperm parameters, and sex hormones. Initially, the latent class trajectory model (LCTM) was utilized to analyze the trajectories of urinary metals. Subsequently, the effects of urinary metal trajectories on semen parameters and sex hormones were examined using the linear mixed model. Finally, the impact of urinary metal trajectories on the classification of semen quality (normal or abnormal) was evaluated using the generalized linear mixed model. RESULTS: Among the 18 metals/metalloids studied, trajectories were formed by 6 of them (Li, Al, Fe, Zn, As, Rb). Further analysis using the linear mixed model and the generalized linear mixed model revealed that Li was negatively correlated with semen volume, and sperm motility (P<0.05). The maximum-decreasing trajectory group had a detrimental effect on semen quality (OR=1.75, 95%CI: 1.22, 2.53) compared to the minimum-stable trajectory group. Al showed negative associations with sperm concentration, total sperm count, and normal morphology (P<0.05). Rb was positively associated with progressive motility (P<0.05). The high-stable trajectory group exhibited a protective effect on semen quality (OR=0.66, 95%CI: 0.49, 0.90) compared to the low-stable trajectory group. Additionally, Fe was observed to have a negative relationship with follicle-stimulating hormone (FSH) (P<0.05), and Rb exhibited a negative correlation with progesterone (P) (P<0.05). CONCLUSION: Our three-year cohort study provides new evidence that Li and Al have a negative impact on semen quality, whereas Rb is associated with beneficial effects. Additionally, Rb and Fe are endocrine disruptors of sex hormones.

Magnesium malate-modified calcium phosphate bone cement promotes the repair of vertebral bone defects in minipigs via regulating CGRP.

Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability, and ability to fill various shaped bone defects. However, its low osteoinductive capacity limits bone regeneration applications. Effectively integrating osteoinductive magnesium ions with CPC remains a challenge. Herein, we developed magnesium malate-modified CPC (MCPC). Incorporating 5% magnesium malate significantly enhances the compressive strength of CPC to (6.18 ± 0.49) MPa, reduces setting time and improves disintegration resistance. In vitro, MCPC steadily releases magnesium ions, promoting the proliferation of MC3T3-E1 cells without causing significant apoptosis, proving its biocompatibility. Molecularly, magnesium malate prompts macrophages to release prostaglandin E2 (PGE2) and synergistically stimulates dorsal root ganglion (DRG) neurons to synthesize and release calcitonin gene-related peptide (CGRP). The CGRP released by DRG neurons enhances the expression of the key osteogenic transcription factor Runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells, promoting osteogenesis. In vivo experiments using minipig vertebral bone defect model showed MCPC significantly increases the bone volume fraction, bone density, new bone formation, and proportion of mature bone in the defect area compared to CPC. Additionally, MCPC group exhibited significantly higher levels of osteogenesis and angiogenesis markers compared to CPC group, with no inflammation or necrosis observed in the hearts, livers, or kidneys, indicating its good biocompatibility. In conclusion, MCPC participates in the repair of bone defects in the complex post-fracture microenvironment through interactions among macrophages, DRG neurons, and osteoblasts. This demonstrates its significant potential for clinical application in bone defect repair.

Enhanced properties of the mid-infrared superluminescent emitter with a composite waveguide.

This study reports on a composite structure composing tilted taper, and tilted and curved waveguides with the aim of enhancing the spectral width and output power of mid-infrared quantum cascade superluminescent emitters (QC-SLEs). The computational results indicate that a tilt angle of 10° and a curved angle of 20° can avoid the selectivity of a certain wavelength due to interference effects at tilt angles of 6° and 8°, resulting in the minimum reflectivity of 1.3×10-4 and 4.4×10-4 for each wide and narrow cavity surface. Simultaneously, the modes propagating perpendicular to the cavity surface exist the least. The corresponding experimental results show a significant enhancement in the spectral width to 168.5c m -1 and a high power output of 5.1 mW for the device. This study presents what we believe to be a novel concept for the designing of superluminescent emitters with both a broadband and high power output.

Plasma THBS1 as a predictive biomarker for poor prognosis and brain metastasis in patients with HER2-enriched breast cancer.

BACKGROUND: Thrombospondin-1 (THBS1) is a secretory adhesive glycoprotein involved in the progression of multiple malignancies, including breast cancer. However, the clinical significance and prognostic role of plasma THBS1 in breast cancer have yet to be clarified. METHODS: Plasma THBS1 levels in 627 breast cancer patients were analyzed by enzyme-linked immunosorbent assay. Bone marrow blood was drawn from the anterior/posterior superior iliac spine to detect the presence of disseminated tumor cells (DTCs). The effects of plasma THBS1 on the clinicopathological characteristics and survival prediction of breast cancer patients were explored. RESULTS: Plasma THBS1 did not correlate with overall survival, breast cancer-specific survival (BCSS), and distant disease-free survival (DDFS) in the entire breast cancer cohort. Notably, HER2-enriched patients with high-plasma THBS1 levels had significantly shorter BCSS (P = 0.027) and DDFS (P = 0.011) than those with low levels. Multivariate analyses revealed that plasma THBS1 was an independent prognostic marker of BCSS (P = 0.026) and DDFS (P = 0.007) in HER2-enriched patients. THBS1 levels were 24% higher in positive DTC patients than in negative DTC patients (P = 0.031), and high levels were significantly associated with poor BCSS in positive DTC patients (HR 2.08, 95% CI 1.17-3.71; P = 0.019). Moreover, high-plasma THBS1 levels were specifically associated with an increased occurrence of brain metastasis in HER2-enriched patients (P = 0.041). CONCLUSION: These findings suggest that plasma THBS1 may be serving as an unfavorable prognosis predictor for HER2-enriched breast cancer and justifies the need for further research.

Short-term exposure to air pollution on peripheral white blood cells and inflammation biomarkers: a cross-sectional study on rural residents.

Effects of short-term exposure to ambient air pollution on systemic immunological and inflammatory biomarkers in rural population have not been adequately characterized. From May to July 2021, 5816 participants in rural villages of northern Henan Province, China, participated in this cross-sectional study. Blood biomarkers of systemic inflammation were determined including peripheral white blood cells (WBC), eosinophils (EOS), basophils (BAS), monocytes (MON), lymphocytes (LYM), neutrophils (NEU), neutrophil-lymphocyte ratio (NLR), and serum high-sensitivity C-reactive protein (hs-CRP). The concentrations of ambient fine particulate matter (PM2.5), PM10, nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) were assessed up to 7 days prior to the blood draw. A generalized linear model was used to analyze the associations between air pollution exposure and the above-mentioned blood biomarkers. Significantly positive associations were revealed between PM2.5, CO and WBC; CO, O3 and LYM; PM2.5, PM10, SO2, CO and NEU; PM2.5, PM10, SO2, CO and NLR; PM2.5, PM10, SO2, NO2, CO, O3 and hs-CRP. Meanwhile, negative associations were found between SO2 and WBC; PM2.5, PM10, NO2, CO, or O3 and EOS; PM2.5, SO2, or CO and BAS; SO2, NO2 or O3 and MON; PM2.5, PM10, SO2, or NO2 and LYM. Moreover, men, individuals with normal body mass index (BMI), current smokers, and those older than 60 years were found vulnerable to air pollution effects. Taken together, short-term exposure to air pollution was associated with systemic inflammatory responses, providing insight into the potential mechanisms for air pollution-induced detrimental systemic effects in rural residents.

Maternal tobacco exposure during pregnancy and atopic dermatitis in offspring: A systematic review and meta-analysis.

The main purpose of this review was to examine the evidence of the relationship between active smoking or passive smoking during pregnancy and atopic dermatitis in offspring. The protocol was written following the PRISMA Checklist and was registered in the PROSPERO database (registration number CRD42022381136). We implemented a comprehensive search in PubMed, Embase and Web of Science databases to identify all potentially related articles from inception through 1 December 2022. We assessed cohort studies and case-control studies using the Newcastle-Ottawa Scale (NOS), and the Joanna Briggs Institute (JBI) critical appraisal tool to assess the quality of cross-sectional studies. Heterogeneity was investigated by using Cochrane Q tests and I2 statistics. In addition, according to the research design, population source and population size, the reasons for the heterogeneity were analysed. A total of 15 observational studies were included in this analysis. Our meta-analysis suggests that atopic dermatitis in offspring is not associated with active smoking during pregnancy (pooled OR, 0.96 [95% CI 0.86-1.07]); however, it is related to passive smoking (OR, 1.52 [95% CI 1.36-1.70]). Passive smoking during pregnancy is associated with an increased risk of eczema development in offspring. More research is needed to explore the risk of active smoking and eczema development in offspring, especially the association between measurements of pregnancy cotinine levels in maternal body fluids and AD in offspring.

PM2.5 exposure upregulates pro-inflammatory protein expression in human microglial cells via oxidant stress and TLR4/NF-κB pathway.

Exposure to ambient PM2.5 is associated with neurodegenerative disorders, in which microglia activation plays a critical role. Thus far, the underlying mechanisms for PM2.5-induced microglia activation have not been well elucidated. In this study, a human microglial cell line (HMC3) was used as the in vitro model to examine the inflammatory effect (hall marker of microglia activation) of PM2.5 and regulatory pathways. The expression of inflammatory mediators including interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) as well as the brain derived neurotrophic factor (BDNF) were determined by ELISA and/or real-time PCR, respectively. Flow cytometry was used to measure the production of intracellular reactive oxygen species (ROS). Western blot was used to measure protein levels of Toll-like receptor 4 (TLR4), NF-κB inhibitor α (IκBα) and COX-2. It was shown that PM2.5 stimulation increased IL-6 and COX-2 expression but decreased BDNF expression in a dose-dependent manner. Further studies showed that PM2.5 triggered the formation of ROS and pre-treatment with the ROS scavenger acetylcysteine (NAC) significantly suppressed PM2.5-induced IL-6 and COX-2 expression. Moreover, the nuclear factor kappa B (NF-κB) inhibitor BAY11-7085 or the TLR4 neutralizing antibody markedly blocked PM2.5-induced IL-6 and COX-2 expression. However, NAC or BAY11-7085 exhibited minimal effect on PM2.5-induced BDNF down-regulation. In addition, pre-treatment with BAY11-7085 or TLR4 neutralizing antibody reduced ROS production induced by PM2.5, and NAC pre-treatment inhibited TLR4 expression and NF-κB activation induced by PM2.5. Collectively, PM2.5 treatment induced IL-6 and COX-2 but suppressed BDNF expression. PM2.5-induced IL-6 and COX-2 expression was mediated by interactive oxidative stress and TLR4/NF-κB pathway.

Combined transcriptome and microbiome analysis reveals the thyrotoxic effects of PM2.5 in female rats.

Pervasive environmental pollutants, specifically particulate matter (PM2.5), possess the potential to disrupt homeostasis of female thyroid hormone (TH). However, the precise mechanism underlying this effect remains unclear. In this study, we established a model of PM2.5-induced thyroid damage in female rats through intratracheal instillation and employed histopathological and molecular biological methods to observe the toxic effects of PM2.5 on the thyroid gland. Transcriptome gene analysis and 16S rRNA sequencing were utilized to investigate the impact of PM2.5 exposure on the female rat thyroid gland. Furthermore, based on the PM2.5-induced toxic model in female rats, we evaluated its effects on intestinal microbiota, TH levels, and indicators of thyroid function. The findings revealed that PM2.5 exposure induced histopathological damage to thyroid tissue by disrupting thyroid hormone levels (total T3 [TT3], (P < 0.05); total T4 [TT4], (P < 0.05); and thyrotropin hormone [TSH], (P < 0.05)) and functional indices (urine iodine [UI], P > 0.05), thus further inducing histopathological injuries. Transcriptome analysis identified differentially expressed genes (DEGs), primarily concentrated in interleukin 17 (IL-17), forkhead box O (FOXO), and other signaling pathways. Furthermore, exposure to PM2.5 altered the composition and abundance of intestinal microbes. Transcriptome and microbiome analyses demonstrated a correlation between the DEGs within these pathways and the flora present in the intestines. Moreover, 16 S rRNA gene sequencing analysis or DEGs combined with thyroid function analysis revealed that exposure to PM2.5 significantly induced thyroid hormone imbalance. We further identified key DEGs involved in thyroid function-relevant pathways, which were validated using molecular biology methods for clinical applications. In conclusion, the homeostasis of the "gut-thyroid" axis may serve as the underlying mechanism for PM2.5-induced thyrotoxicity in female rats.

Grape seed proanthocyanidin extract alleviates inflammation in experimental colitis mice by inhibiting NF-κB signaling pathway.

Ulcerative colitis (UC) is a complex inflammatory disease of colorectum that induces abnormal immune responses and severely affects the quality of life of the patients. Grape seed proanthocyanidin extract (GSPE) exerts anti-inflammatory and antioxidant functions in many inflammatory diseases. The objective of this study was to investigate the potential therapeutic effects and underlying mechanisms of GSPE in UC using a dextran sodium sulfate (DSS)-induced mouse UC model and a lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage model. In this study, we found that the GSPE markedly prevented DSS-induced weight loss and colon length shortening in UC mice. Further investigations showed that GSPE significantly attenuated the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß, and elevated the expression of anti-inflammatory cytokine IL-10 in the colon tissues and serum of DSS-induced colitis mice by suppressing NF-κB signaling pathway. Furthermore, LPS-induced inflammation in RAW264.7 cells was also reversed by GSPE. Taken together, our results confirm that GSPE can ameliorate inflammatory response in experimental colitis via inhibiting NF-κB signaling pathway. This study advances the research progress on a potentially effective therapeutic strategy for inflammatory bowel diseases.

TAK-242 improves sepsis-associated acute kidney injury in rats by inhibiting the TLR4/NF-κB signaling pathway.

OBJECTIVE: This study was designed to observe the effect of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway activity on sepsis-associated acute kidney injury (SA-AKI), thereby providing new considerations for the prevention and treatment of SA-AKI. METHODS: The rats were divided into Sham, cecal ligation and puncture (CLP), CLP + vehicle, and CLP + TAK-242 groups. Except the Sham group, a model of CLP-induced sepsis was established in other groups. After 24 h, the indicators related to kidney injury in blood samples were detected. The pathological changes in the kidneys were observed by hematoxylin-eosin staining, and tubular damage was scored. Oxidative stress-related factors, mitochondrial dysfunction-related indicators in each group were measured; the levels of inflammatory factors in serum and kidney tissue of rats were examined. Finally, the expression of proteins related to the TLR4/NF-κB signaling pathway was observed by western blot. RESULTS: Compared with the CLP + vehicle and CLP + TAK-242 groups, the CLP + TAK-242 group reduced blood urea nitrogen (BUN), creatinine (Cr), cystatin-C (Cys-C), reactive oxygen species (ROS), malondialdehyde (MDA), and inflammatory factors levels (p < 0.01), as well as increased superoxide dismutase (SOD) activity of CLP rats (p < 0.01). Additionally, TAK-242 treatment improved the condition of CLP rats that had glomerular and tubular injuries and mitochondrial disorders (p < 0.01). Further mechanism research revealed that TAK-242 can inhibit the TLR4/NF-κB signaling pathway activated by CLP (p < 0.01). Above indicators after TAK-242 treatment were close to those of the Sham group. CONCLUSION: TAK-242 can improve oxidative stress, mitochondrial dysfunction, and inflammatory response by inhibiting the activity of TLR4/NF-κB signaling pathway, thereby preventing rats from SA-AKI.

Platelet-derived extracellular vesicles promote endothelial dysfunction in sepsis by enhancing neutrophil extracellular traps.

BACKGROUND: The role of platelet-derived extracellular vesicles (PEVs) in the development of sepsis was investigated in this study. METHODS: After collection of blood samples from sepsis patients and normal volunteers, the extracellular vesicles (EVs) were separated, followed by the isolation of PEVs from the blood of rats. Next, a sepsis rat model was constructed by cecal ligation and puncture (CLP), and rats received tail vein injection of PEVs to explore the role of PEVs in sepsis. Subsequently, nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) were adopted to determine the diameter of EVs and observe the morphology of PEVs, respectively; flow cytometry to detect the percentage of CD41-and CD61-positive EVs in isolated EVs; and ELISA to assess neutrophil extracellular trap (NET) formation, endothelial function injury-related markers in clinical samples or rat blood and serum inflammatory factor level. RESULTS: Compared with normal volunteers, the percentage of CD41- and CD61-positive EVs and the number of EVs were significantly elevated in sepsis patients. Moreover, sepsis patients also presented notably increased histone H3, myeloperoxidase (MPO), angiopoietin-2 and endocan levels in the blood, and such increase was positively correlated with the number of EVs. Also, animal experiments demonstrated that PEVs significantly promoted NET formation, mainly manifested as up-regulation of histone H3, high mobility group protein B1 (HMGB1), and MPO; promoted endothelial dysfunction (up-regulation of angiopoietin-2, endocan, and syndecan-1); and stimulated inflammatory response (up-regulation of interleukin (IL) -1ß, IL-6, tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein (MCP) -1) in the blood of sepsis rats. CONCLUSION: PEVs aggravate endothelial function injury and inflammatory response in sepsis by promoting NET formation.

Air pollution associated acute respiratory inflammation and modification by GSTM1 and GSTT1 gene polymorphisms: a panel study of healthy undergraduates.

Epidemiological evidence has linked air pollution with adverse respiratory outcomes, but the mechanisms underlying susceptibility to air pollution remain unclear. This study aimed to investigate the role of glutathione S-transferase (GST) polymorphism in the association between air pollution and lung function levels. A total of 75 healthy young volunteers aged 18-20 years old were recruited for six follow-up visits and examinations. Spirometry was conducted to obtain lung function parameters such as forced vital capacity (FVC), and forced expiratory volume in 1 s (FEV1). Nasal fluid concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and 8-epi-prostaglandin F2α (8-epi-PGF2a) were measured using ELISA kits. Linear mixed-effect models were used to evaluate the association of air pollutants with respiratory outcomes. Additionally, polymorphisms of glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) were estimated to explore its role in the association between air pollutants and lung function. We found that short-term exposure to atmospheric particulates such as PM2.5 and PM10 can cause an increase in nasal biomarkers of inflammation, oxidative stress, and lung function, while air gaseous pollutant exposure is linked with decreased lung function, except for CO. Stratification analyses showed that an increase in nasal inflammatory cytokines caused by exposure to atmospheric particulates is more obvious in subjects with GSTM1-sufficient (GSTM1+) than GSTM1-null (GSTM1-), while elevated lung function levels due to air particles are more significant in subjects with the genotype of GSTM1- when compared to GSTM1+. As for air gaseous pollutants, decreased lung function levels caused by O3, SO2, and NO2 exposure is more manifest in subjects with the genotype of GSTM1- compared to GSTM1+. Taken together, short-term exposure to air pollutants is associated with alterations in nasal biomarkers and lung function levels in young healthy adults, and susceptible genotypes play an important mediation role in the association between exposure to air pollutants and inflammation, oxidative stress, and lung function levels.

Geldanamycin ameliorates multiple organ dysfunction and microthrombosis in septic mice by inhibiting the formation of the neutrophil extracellular network by activating heat shock factor 1 HSF1.

Sepsis and septic shock are common critical illnesses in the intensive care unit with a high mortality rate. Geldanamycin (GA) has a broad spectrum of antibacterial and antiviral activity and has inhibitory effects on various viruses. However, whether GA affects sepsis due to infections remains unknown. In this study, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen and creatinine in serum; neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 in the urine, cytokines (tumour necrosis factor alpha, interleukin-1ß and interleukin-6) in the bronchoalveolar lavage fluid and myeloperoxidase in the lung tissues were measured using enzyme-linked immunosorbent assay kits. Pathological injury was measured by hematoxylin and eosin staining and neutrophils were measured by flow cytometry analysis; related expressions were analysed by qPCR, western blot and immunofluorescence assay. The results showed that GA significantly ameliorated cecum ligation and puncture (CLP)-triggered liver, kidney and lung injury in septic mice. In addition, we found that GA dose-dependently inhibited microthrombosis and alleviated coagulopathy in septic mice. Further molecular mechanism analysis suggests that GA may act through upregulation of heat shock factor 1 and tissue-type plasminogen activator. In conclusion, our study elucidated the protective effects of GA in a mouse model established using CLP, and the results reveal that GA may be a promising agent for sepsis.

Output characteristics of distributed feedback 3.0 terahertz quantum cascade lasers.

Distributed feedback quantum cascade lasers lased at 3.0 THz were prepared and their output performance was analyzed. The optimized grating parameters were obtained by theoretical analyses. Single-mode emission was obtained and a maximum output power of more than 166 mW at 15 K was achieved. The corresponding threshold current density was 257A/c m 2, and the side-mode suppression ratio was more than 15 dB. By changing the input voltage, the frequency was stable with a variation of less than 3 GHz. A beam with obviously fast and slow axis features was observed. Further improvement and the potential application of distributed feedback quantum cascade lasers are discussed.

The effect of warming ropivacaine on ultrasound-guided subgluteal sciatic nerve block: a randomized controlled trial.

BACKGROUND: There is a long latent period for the sciatic nerve block before a satisfactory block is attained. Changes in the temperature of local anesthetics may influence the characters of the peripheral nerve block. This study was designed to evaluate the effect of warming ropivacaine on the ultrasound-guided subgluteal sciatic nerve block. METHODS: Fifty-four patients for distal lower limbs surgery were randomly allocated into warming group (group W, n = 27) or room tempeture group (group R, n = 27) with the ultrasound-guided subgluteal sciatic nerve block. The group W received 30 ml of ropivacaine 0.5% at 30℃ and the group R received 30 ml of ropivacaine 0.5% at 23℃. The sensory and motor blockade were assessed every 2 min for 30 min after injection. The primary outcome was the onset time of limb sensory blockade. RESULTS: The onset time of sensory blockade was shorter in group W than in group R (16 (16,18) min vs 22 (20,23) min, p < 0.001), and the onset time of motor blockade was also shorter in group W than in group R (22 (20,24) min vs 26 (24,28) min, p < 0.001). The onset time of sensory blockade for each nerve was shorter in group W than in group R (p < 0.001). No obvious differences for the duration of sensory and motor blockade and the patient satisfaction were discovered between both groups. No complications associated with nerve block were observed 2 days after surgery. CONCLUSIONS: Warming ropivacaine 0.5% to 30℃ accelerates the onset time of sensory and motor blockade in the ultrasound-guided subgluteal sciatic nerve block and it has no influence on the duration of sensory and motor blockade. TRIAL REGISTRATION: The trial was registered on October 3, 2022 in the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/bin/project/edit?pid=181104 ), registration number ChiCTR2200064350 (03/10/2022).

Preservation vs. dissection of inferior pulmonary ligament for thoracoscopic upper lobectomy: a prospective randomized controlled trial.

OBJECTIVES: The proper procedure for inferior pulmonary ligament (IPL) during upper lobectomy remains a topic of debate. To address this matter, we carried out a trial comparing the clinical outcomes of IPL preservation versus IPL dissection during thoracoscopic upper lobectomy (TUL). METHODS: Patients undergoing thoracoscopic left/right upper lobectomy (TLUL/TRUL) were assigned to either the dissection group (Group D) or the preservation group (Group P). Our primary objective was to quantify and compare the alterations in postoperative residual bronchial angle and lung volume changes between the two groups. Our secondary objective encompassed the assessment of various other intraoperative and postoperative outcomes. RESULTS: Following adherence to the inclusion and exclusion criteria, we enrolled 100 patients (41 left and 59 right) in Group P and 108 patients (41 left and 67 right) in Group D for the study. Our findings revealed that in TLUL, Group P was able to reduce the degree of postoperative residual bronchial angle change (P < 0.05). Conversely, the situation was distinct for TRUL. We found no notable disparity between the two groups (P > 0.05) with regard to alterations in lung volume or the occurrence of postoperative complications-except for the duration of postoperative hospital stay (P < 0.05). CONCLUSIONS: Our study suggests IPL preservation especially for TLUL when compared to TRUL, which have important implications for the clinical management of patients undergoing upper lobectomy.

Biomechanical study of the stiffness of the femoral locking compression plate of an external fixator for lower tibial fractures.

BACKGROUND: A locking compression plate (LCP) of the distal femur is used as an external fixator for lower tibial fractures. However, in clinical practice, the technique lacks a standardized approach and a strong biomechanical basis for its stability. METHODS: In this paper, internal tibial LCP fixator (Group IT-44), external tibial LCP fixator (Group ET-44), external distal femoral LCP fixator (Group EF-44, group EF-33, group EF-22), and conventional external fixator (Group CEF-22) frames were used to fix unstable fracture models of the lower tibial segment, and anatomical studies were performed to standardize the operation as well as to assess the biomechanical stability and adjustability of the distal femoral LCP external fixator by biomechanical experiments. RESULTS: It was found that the torsional and flexural stiffnesses of group EF-44 and group EF-33 were higher than those of group IT-44 and group ET-44 (p < 0.05); the flexural stiffness of group EF-22 was similar to that of group IT-44 (p > 0.05); and the compressive stiffness of all three EF groups was higher than that of group ET-44 (p < 0.05). In addition, the flexural and compressive stiffnesses of the three EF groups decreased with the decrease in the number of screws (p < 0.05), while the torsional stiffness of the three groups did not differ significantly between the two adjacent groups (p > 0.05). Group CEF-22 showed the highest stiffnesses, while group ET-44 had the lowest stiffnesses (P < 0.05). CONCLUSIONS: The study shows that the distal femoral LCP has good biomechanical stability and adjustability and is superior to the tibial LCP as an external fixator for distal tibial fractures, as long as the technique is used in a standardized manner according to the anatomical studies in this article.

Association between short-term exposure to PM2.5 and nasal microbiota dysbiosis, inflammation and oxidative stress: A panel study of healthy young adults.

Fine particulate matter (PM2.5) is the primary environmental stressor and a significant threat to public health. However, the effect of PM2.5 exposure on human nasal microbiota and its pathophysiological implication remain less understood. This study aimed to explore the associations of PM2.5 exposure with indices of nasal microbiota and biomarkers of nasal inflammation and oxidative stress. We conducted a panel study with 75 students in Xinxiang, Henan Province, China, from September to December 2017. Biomarkers of nasal inflammation and oxidative stress including interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), 8-epi-prostaglandin F2 alpha (8-epi-PGF2α) and indices of nasal microbiota diversity and phenotypes were measured. Linear mixed-effect models and bioinformatic analyses were performed to assess the association of PM2.5 concentrations with the abovementioned biomarkers and indices. It was found that per 1 µg/m3 increase in PM2.5 was associated with increments of 13.15% (95 % CI: 5.53-20.76 %) and 78.98 % (95 % CI: 21.61-136.36 %) in TNF-α on lag2 and lag02. Indices of microbial diversity and phenotypes including equitability, Shannon index, biofilm forming, and oxidative stress tolerant decreased to different extent with the increment in PM2.5. Notably, thirteen differential microbes in Clostridia, Bacilli, and Gammaproteobacteria classes were recognized as keystone taxa and eight of them were associated with TNF-α, IL-6, or 8-epi-PGF2α. Moreover, environmental adaptation was the most critical functional pathway of nasal microbiota associated with PM2.5 exposure. In summary, short-term exposure to PM2.5 is associated with nasal inflammation, microbiota diversity reduction, and the microbiota phenotype alterations.