Ameliorative Effect of Morinda Officinalis Oligosaccharides on LPS-Induced Acute Lung Injury.

Acute lung injury (ALI) is a disease characterized by extensive lung damage and rampant inflammation, with a high mortality rate and no effective treatments available. Morinda officinalis oligosaccharides (MOOs), derived from the root of the traditional Chinese medicinal herb Morinda officinalis, known for its immune-boosting properties, presents a novel therapeutic possibility. To date, the impact of MOOs on ALI has not been explored. Our study aimed to investigate the potential protective effects of MOOs against ALI and to uncover the underlying mechanisms through an integrated approach of network pharmacology, molecular docking, and experimental validation. We discovered that MOOs significantly mitigated the pathological damage and decreased the expression of pro-inflammatory cytokines in LPS-induced ALI in mice. Complementary in vitro studies further demonstrated that MOOs effectively attenuated the M1 polarization induced by LPS. Network pharmacology analysis identified HSP90AA1, HSP90AB1, and NF-κB as key overlapping targets within a protein-protein interaction (PPI) network. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses elucidated the biological processes and signaling pathways implicated in MOOs' therapeutic action on ALI. Subsequently, molecular docking affirmed the binding of MOOs to the active sites of these identified targets. Corroborating these findings, our in vivo and in vitro experiments consistently demonstrated that MOOs significantly inhibited the LPS-induced upregulation of HSP90 and NF-κB. Collectively, these findings suggest that MOOs confer protection against ALI through a multi-target, multi-pathway mechanism, offering a promising new therapeutic strategy to mitigate this severe pulmonary condition.

Special issue "The advance of solid tumor research in China": Participants with a family history of cancer have a higher participation rate in low-dose computed tomography for lung cancer screening.

We aimed to determine participation in low-dose computed tomography (LDCT) of individuals with a family history of common cancers in a population-based screening program to provide timely evidence in high-risk populations in China. The analysis was conducted using data from the Cancer Screening Program in Urban China (CanSPUC), which recruited 282 377 participants aged 40 to 74 years from eight cities in the Henan province. Using the CanSPUC risk score system, 55 428 participants were evaluated to have high risk for lung cancer and were recommended for LDCT. We calculated the overall and group-specific participation rates using family history of common cancers and compared differences in participation rates between different groups. Odds ratios (ORs) and 95% confidence intervals were derived by multivariable logistic regression. Of the 55 428 participants, 22 260 underwent LDCT (participation rate, 40.16%). Family history of lung, esophageal, stomach, liver and colorectal cancer was associated with increased participation in LDCT screening. The odds of participants with a family history of one, two, three and four or more cancer cases undergoing LDCT screening were 1.9, 2.7, 2.8 and 3.5 times, respectively, than those without a family history of cancer. Compared to those without a history of cancer, participation in LDCT gradually increased as the number of cancer cases in the family increased (P < .001). Our findings suggest that there is room for improvement in lung cancer screening given the relatively low participation rate. Lung cancer screening in populations with a family history of cancer may improve efficiency and cost-effectiveness; however, this requires further verification.

Dual Antiplatelet Therapy vs Alteplase for Patients With Minor Nondisabling Acute Ischemic Stroke: The ARAMIS Randomized Clinical Trial.

Importance: Intravenous thrombolysis is increasingly used in patients with minor stroke, but its benefit in patients with minor nondisabling stroke is unknown. Objective: To investigate whether dual antiplatelet therapy (DAPT) is noninferior to intravenous thrombolysis among patients with minor nondisabling acute ischemic stroke. Design, Setting, and Participants: This multicenter, open-label, blinded end point, noninferiority randomized clinical trial included 760 patients with acute minor nondisabling stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤5, with ≤1 point on the NIHSS in several key single-item scores; scale range, 0-42). The trial was conducted at 38 hospitals in China from October 2018 through April 2022. The final follow-up was on July 18, 2022. Interventions: Eligible patients were randomized within 4.5 hours of symptom onset to the DAPT group (n = 393), who received 300 mg of clopidogrel on the first day followed by 75 mg daily for 12 (±2) days, 100 mg of aspirin on the first day followed by 100 mg daily for 12 (±2) days, and guideline-based antiplatelet treatment until 90 days, or the alteplase group (n = 367), who received intravenous alteplase (0.9 mg/kg; maximum dose, 90 mg) followed by guideline-based antiplatelet treatment beginning 24 hours after receipt of alteplase. Main Outcomes and Measures: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1 (range, 0-6), at 90 days. The noninferiority of DAPT to alteplase was defined on the basis of a lower boundary of the 1-sided 97.5% CI of the risk difference greater than or equal to -4.5% (noninferiority margin) based on a full analysis set, which included all randomized participants with at least 1 efficacy evaluation, regardless of treatment group. The 90-day end points were assessed in a blinded manner. A safety end point was symptomatic intracerebral hemorrhage up to 90 days. Results: Among 760 eligible randomized patients (median [IQR] age, 64 [57-71] years; 223 [31.0%] women; median [IQR] NIHSS score, 2 [1-3]), 719 (94.6%) completed the trial. At 90 days, 93.8% of patients (346/369) in the DAPT group and 91.4% (320/350) in the alteplase group had an excellent functional outcome (risk difference, 2.3% [95% CI, -1.5% to 6.2%]; crude relative risk, 1.38 [95% CI, 0.81-2.32]). The unadjusted lower limit of the 1-sided 97.5% CI was -1.5%, which is larger than the -4.5% noninferiority margin (P for noninferiority <.001). Symptomatic intracerebral hemorrhage at 90 days occurred in 1 of 371 participants (0.3%) in the DAPT group and 3 of 351 (0.9%) in the alteplase group. Conclusions and Relevance: Among patients with minor nondisabling acute ischemic stroke presenting within 4.5 hours of symptom onset, DAPT was noninferior to intravenous alteplase with regard to excellent functional outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT03661411.

Effect of Argatroban Plus Intravenous Alteplase vs Intravenous Alteplase Alone on Neurologic Function in Patients With Acute Ischemic Stroke: The ARAIS Randomized Clinical Trial.

Importance: Previous studies suggested a benefit of argatroban plus alteplase (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke (AIS). However, robust evidence in trials with large sample sizes is lacking. Objective: To assess the efficacy of argatroban plus alteplase for AIS. Design, Setting, and Participants: This multicenter, open-label, blinded end point randomized clinical trial including 808 patients with AIS was conducted at 50 hospitals in China with enrollment from January 18, 2019, through October 30, 2021, and final follow-up on January 24, 2022. Interventions: Eligible patients were randomly assigned within 4.5 hours of symptom onset to the argatroban plus alteplase group (n = 402), which received intravenous argatroban (100 µg/kg bolus over 3-5 minutes followed by an infusion of 1.0 µg/kg per minute for 48 hours) within 1 hour after alteplase (0.9 mg/kg; maximum dose, 90 mg; 10% administered as 1-minute bolus, remaining infused over 1 hour), or alteplase alone group (n = 415), which received intravenous alteplase alone. Both groups received guideline-based treatments. Main Outcomes and Measures: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 1 at 90 days. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 817 eligible patients with AIS who were randomized (median [IQR] age, 65 [57-71] years; 238 [29.1%] women; median [IQR] National Institutes of Health Stroke Scale score, 9 [7-12]), 760 (93.0%) completed the trial. At 90 days, 210 of 329 participants (63.8%) in the argatroban plus alteplase group vs 238 of 367 (64.9%) in the alteplase alone group had an excellent functional outcome (risk difference, -1.0% [95% CI, -8.1% to 6.1%]; risk ratio, 0.98 [95% CI, 0.88-1.10]; P = .78). The percentages of participants with symptomatic intracranial hemorrhage, parenchymal hematoma type 2, and major systemic bleeding were 2.1% (8/383), 2.3% (9/383), and 0.3% (1/383), respectively, in the argatroban plus alteplase group and 1.8% (7/397), 2.5% (10/397), and 0.5% (2/397), respectively, in the alteplase alone group. Conclusions and Relevance: Among patients with acute ischemic stroke, treatment with argatroban plus intravenous alteplase compared with alteplase alone did not result in a significantly greater likelihood of excellent functional outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT03740958.

Mitochondrial DNA plays an important role in lung injury induced by sepsis.

The effects and mechanisms of mitochondrial DNA (mtDNA) in the development of sepsis-induced lung injury is not well understood. In our present study, we studied the mtDNA effects in sepsis-induced lung injury model, in vitro and in vivo. Compared with the Normal group, the lung histopathological score, the number of positive apoptosis cell, wet/dry (W/D) ratio and TNF-α, IL-1ß, and IL-6 concentrations of lipopolysaccharides (LPSs) and mtDNA groups were significantly increased (P < 0.001, respectively). Meanwhile, the lung histopathological score, positive W/D ratio, number of apoptosis cell and tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6 concentrations of LPS + mtDNA and small interfering RNA (siRNA)-NC + LPS + mtDNA groups were significantly upregulated compared with those of LPS group (P < 0.05, respectively). However, the lung histopathological score, the number of positive apoptosis cell, W/D ratio and TNF-α, IL-1ß, and IL-6 concentrations were significantly improved within the toll-like receptor (TLR9)siRNA + LPS + mtDNA group compared with the LPS group (P < 0.01, respectively). The TLR9, MyD88, and NF-κB proteins or gene expressions of the LPS group and mtDNA group were significantly upregulated compared with those of Normal group by Western blot analysis or immunohistochemistry assay (P < 0.01, respectively), and the TLR9, MyD88, and NF-κB proteins or gene expressions of LPS + mtDNA and siRNA-NC + LPS + mtDNA groups were significantly enhanced compared with those of LPS group (P < 0.05, respectively). However, the TLR9, MyD88, and NF-κB proteins or gene expressions of TLR9siRNA + LPS + mtDNA group were significantly suppressed compared with those of the LPS group (P < 0.01, respectively). In conclusion, mtDNA could provoke lung injury induced by sepsis via regulation of TLR9/MyD88/NF-κB pathway in vitro and in vivo.

Volume changes of biochar-amended landfill cover soil under a thermal cycle.

Biochar has been identified as a favourable amendment for landfill cover soils. So far, the effects of biochar on soil response to temperature variations are still unclear. Waste heat generates when municipal solid waste decomposes, and the temperature of landfill can increase up to 90°C. The present study aims to investigate the thermally induced volumetric behaviour of biochar-amended sand with different biochar application ratios of 0%, 5% and 10%. Experimental results show that, during heating from 23-83°C, pure sand expands. However, during the heating process biochar-amended sand samples contract first and then expand. This is because biochar treatment not only decreases soil density, but also promotes the formation of big size macro-aggregations with more macro-pores, which may be destroyed when particle rearrangements induced by thermal expansion occur. During the cooling process from 83-23°C, all the specimens with three biochar application ratios show contraction. Moreover, with an increasing biochar application ratio, the thermal expansion coefficient of the soil specimen decreases. This is because biochar is insensitive to temperature variation as it is produced in very high temperature. Therefore, biochar-amended soil is a promising alternative landfill cover material for municipal solid waste landfill, and the effect of temperature effect on its volume change in landfill cover design is also essential to be considered.

Sleep Homeostasis and General Anesthesia: Are Fruit Flies Well Rested after Emergence from Propofol?

BACKGROUND: Shared neurophysiologic features between sleep and anesthetic-induced hypnosis indicate a potential overlap in neuronal circuitry underlying both states. Previous studies in rodents indicate that preexisting sleep debt discharges under propofol anesthesia. The authors explored the hypothesis that propofol anesthesia also dispels sleep pressure in the fruit fly. To the authors' knowledge, this constitutes the first time propofol has been tested in the genetically tractable model, Drosophila melanogaster. METHODS: Daily sleep was measured in Drosophila by using a standard locomotor activity assay. Propofol was administered by transferring flies onto food containing various doses of propofol or equivalent concentrations of vehicle. High-performance liquid chromatography was used to measure the tissue concentrations of ingested propofol. To determine whether propofol anesthesia substitutes for natural sleep, the flies were subjected to 10-h sleep deprivation (SD), followed by 6-h propofol exposure, and monitored for subsequent sleep. RESULTS: Oral propofol treatment causes anesthesia in flies as indicated by a dose-dependent reduction in locomotor activity (n = 11 to 41 flies from each group) and increased arousal threshold (n = 79 to 137). Recovery sleep in flies fed propofol after SD was delayed until after flies had emerged from anesthesia (n = 30 to 48). SD was also associated with a significant increase in mortality in propofol-fed flies (n = 44 to 46). CONCLUSIONS: Together, these data indicate that fruit flies are effectively anesthetized by ingestion of propofol and suggest that homologous molecular and neuronal targets of propofol are conserved in Drosophila. However, behavioral measurements indicate that propofol anesthesia does not satisfy the homeostatic need for sleep and may compromise the restorative properties of sleep.

Efficacy of limb salvage with primary tumor resection simultaneously for solitary bone metastasis in limbs.

BACKGROUND: This study aims to evaluate the efficacy of limb salvage with primary tumor resection on patients with solitary bone metastasis. METHODS: A retrospective treatment outcome review was performed on 20 patients with solitary bone metastasis as the primary clinical symptom who were admitted to the hospital between 2006 and 2010. With primary tumor resection, 18/20 patients received limb salvage surgery simultaneously. Pain scoring was assessed using the 0 to 10 numerical rating scale. The quality of life scoring was performed before and 3 months after surgery using the SF-30 scoring system. In addition, limb function was assessed 3 months after the operation using the Scoring System of American Musculoskeletal Tumor Society system (MSTS). RESULTS: The pain symptom was significantly ameliorated after the operation (t=26.653, P<0.001), and the quality of life dramatically improved (t=-20.581, P<0.001). The postoperative MSTS scores ranged from 18 to 27. The average score was 23.10±2.36. The Kaplan-Meier analysis showed that no significant differences (χ2=1.589, P=0.207) were observed in the tumor-free survival time between the wide and marginal resections. CONCLUSIONS: The application of the wide or marginal excision for the primary lesion and bony metastasis focus, based on the principles of primary bone tumors, can significantly relieve the pain and improve the quality of life and limb function of patients whose solitary bone metastasis was manifested as the first sign.

α2-Adrenergic stimulation of the ventrolateral preoptic nucleus destabilizes the anesthetic state.

The sleep-promoting ventrolateral preoptic nucleus (VLPO) shares reciprocal inhibitory inputs with wake-active neuronal nuclei, including the locus ceruleus. Electrophysiologically, sleep-promoting neurons in the VLPO are directly depolarized by the general anesthetic isoflurane and hyperpolarized by norepinephrine, a wake-promoting neurotransmitter. However, the integration of these competing influences on the VLPO, a sleep- and anesthetic-active structure, has yet to be evaluated in either brain slices in vitro or the intact organism. Single-cell multiplex RT-PCR conducted on both isoflurane-activated, putative sleep-promoting VLPO neurons and neighboring, state-indifferent VLPO neurons in mouse brain slices revealed widespread expression of α2A-, α2B- and α2C-adrenergic receptors in both populations. Indeed, both norepinephrine and the highly selective α2 agonist dexmedetomidine each reversed the VLPO depolarization induced by isoflurane in slices in vitro. When microinjected directly into the VLPO of a mouse lightly anesthetized with isoflurane, dexmedetomidine increased behavioral arousal and reduced the depressant effects of isoflurane on barrel cortex somatosensory-evoked potentials but failed to elicit spectral changes in spontaneous EEG. Based on these observations, we conclude that local modulation of α-adrenergic activity in the VLPO destabilizes, but does not fully antagonize, the anesthetic state, thus priming the brain for anesthetic emergence.

Factors Affecting the Recurrence of Giant Cell Tumor of Bone After Surgery: A Clinicopathological Study of 80 Cases from a Single Center.

BACKGROUND/AIMS: This aim of the present study was to identify specific markers determining the recurrence of the giant cell tumor of bone (GCTB). METHODS: This study involved the clinicopathological analysis of 80 cases. All of the clinical features, pathological fracture, Campanacci grade, histological features and surgical methods were reviewed. Immunohistochemistry was used to detect the expression of Ki-67, CD147, mutant p53 and p63 in GCTB. Comparisons between different groups were performed using the Chi-square test. The risk factors affecting recurrence were analyzed using a binary logistic model. Kaplan-Meier analysis was employed for the survival analysis between the groups. Cell proliferation assays, migration and invasion assays were used to detect the function of CD147 on GCTB in vitro. RESULTS: The univariate analysis showed that Ki-67 and CD147 expression, pathological fracture, Campanacci grade and surgical method were associated with recurrence. The multivariate analysis revealed that CD147 expression, Campanacci grade and surgical method were the factors affecting GCTB recurrence. In addition, the Kaplan-Meier analysis revealed that these factors affected tumor-free survival time. In vitro study revealed that the CD147 knockdown by small interfering RNA (siRNA) technique dramatically reduced the proliferation, migration and invasion of GCTB. CONCLUSION: Our results suggest that CD147 may serve as an adequate marker for GCTB recurrence. Campanacci grade is a risk factor for GCTB recurrence, which is also affected by the surgical method used.

miR-132 inhibits lipopolysaccharide-induced inflammation in alveolar macrophages by the cholinergic anti-inflammatory pathway.

OBJECTIVE: Although microRNA-132 (miR-132) has been shown to be involved in the inflammatory regulation, its role in sepsis-induced lung injury is unknown. We hypothesized that miR-132 attenuated lipopolysaccharide (LPS)-induced inflammation of alveolar macrophages by targeting acetylcholinesterase (AChE) and enhancing the acetylcholine (ACh)-mediated cholinergic anti-inflammatory response. METHODS: The LPS-treated rat alveolar macrophage cell line NR8383 was used as the inflammatory model. To assess the effect of miR-132, alveolar macrophages were transfected with miR-132 mimic or inhibitor. RESULTS: We found that miR-132 was upregulated in LPS-stimulated alveolar macrophages. Induction of AChE mRNA showed an inverse pattern with respect to AChE protein and activity, suggesting posttranscriptional regulation of AChE. Utilizing miR-132 mimic transfection, we found that overexpression of miR-132 enhanced the ACh-mediated cholinergic anti-inflammatory reaction by targeting AChE mRNA in LPS-treated alveolar macrophages. Blockage of miR-132 using miR-132 inhibitor reversed the Ach action upon LPS-induced release of inflammatory mediators and reduction in AchE protein/activity. Moreover, in the presence of ACh, upregulation of miR-132 suppressed LPS-induced nuclear translocation of NF-κB and production of STAT3 and phosphorylated STAT3, while downregulation of miR-132 enhanced the nuclear translocation of NF-κB. CONCLUSION: We propose that miR-132 functions as a negative regulator of the inflammatory response in alveolar macrophages by potentiating the cholinergic anti-inflammatory pathway, and represents a potential therapeutic leverage point in modulating inflammatory responses.

GSK3ß negatively regulates HIF1α mRNA stability via nucleolin in the MG63 osteosarcoma cell line.

Hypoxia-inducible factor 1α (HIF1α) is a transcription factor involved in the growth, invasion and metastasis of malignant tumors. Glycogen synthase kinase 3 beta (GSK3ß) is a protein kinase involved in a variety of signaling pathways, such as the Wnt and NF-κB pathways; this kinase can affect tumor progress through the regulation of transcription factor expression and apoptosis. Recent studies showed that GSK3ß was involved in the expression of HIF1α. However, the effect of GSK3ß on HIF1α expression in osteosarcoma cells remains unknown. To understand the relationship between GSK3ß and HIF1α comprehensively, small RNA interference techniques, Western blot analyses, quantitative real-time PCR analyses and luciferase assays were used in our study. Experimental data revealed that inhibition of GSK3ß could increase HIF1α protein levels and expression of its target genes by increasing the stability of the HIF1α mRNA, not by affecting the HIF1α protein stability, and that this process could be mediated by nucleolin.

Molecular evidence for nitrite-dependent anaerobic methane-oxidising bacteria in the Jiaojiang Estuary of the East Sea (China).

Nitrite-dependent anaerobic methane oxidation (N-DAMO) is a recently discovered process linking the global carbon and nitrogen cycles. This process was reported to be mediated by "Candidatus Methylomirabilis oxyfera". To date, M. oxyfera-like bacteria have been detected in a limited number of freshwater habitats, but whether these bacteria occur in estuarine habitats is currently unknown. In this study, the distribution, diversity and abundance of M. oxyfera-like bacteria were studied in the sediment of the Jiaojiang Estuary of the East Sea (China). Both the 16S ribosomal RNA (rRNA) and pmoA genes confirmed the occurrence of M. oxyfera-like bacteria in the examined estuary. The recovered 16S rRNA gene sequences showed 91.5-97.2 % identity to the 16S rRNA gene of M. oxyfera, and the recovered pmoA gene sequences showed 85.1-95.4 % identity to the pmoA gene of M. oxyfera. Quantitative PCR further confirmed the occurrence of M. oxyfera-like bacteria in this estuary, with the abundance varying from 5.80 ± 0.28 × 10(4) to 8.35 ± 0.52 × 10(7) copies g (dry weight)(-1). Correlation analysis indicated that the sediment organic content was the most important factor affecting the distribution of M. oxyfera-like bacterial communities in the examined sediments among the environmental factors investigated. This study demonstrated for the first time the existence of M. oxyfera-like bacteria in an estuarine environment and showed the correlations between the distribution of these bacteria and the estuarine environmental conditions.

Mean platelet volume and platelet distribution width in vascular dementia and Alzheimer's disease.

Activated platelets play a substantial role in Alzheimer's disease (AD) and atherothrombosis. Mean platelet volume (MPV) is an early marker of platelet activation, which is linked to a variety of pro-thrombotic and pro-inflammatory diseases. This study is to examine the association between platelet indices and vascular dementia (VaD) and AD. In this cross-sectional study, we investigated the levels of platelet count, MPV, and platelet distribution width (PDW) in 150 VaD patients, 110 AD patients, and 150 non-demented controls. MPV and PDW were significantly lower in patients with VaD and AD as compared with controls. The decrease in PDW for AD patients as compared with VaD patients was also significant (p < 0.001). In addition, there was a positive correlation between Mini-Mental State Examination (MMSE) and MPV and PDW, after adjusting confounding factors (r = 0.532 for MPV and r = 0.425 for PDW, p < 0.001 for both). Multivariate regression analysis showed that MPV and PDW were significantly associated with MMSE (ß = 0.366 for MPV and ß = 0.273 for PDW, p < 0.001 for both). In conclusion, MPV and PDW were both decreased in VaD and AD. PDW levels were significantly lower in AD as compared to those in VaD. Our findings suggest that PDW in combination with MMSE scores could be potential indicators for distinguishing VaD from AD.

Prediction method for the tension force of support ropes in flexible rockfall barriers based on full-scale experiments and numerical analysis.

This paper proposes a prediction method for the tension force of support ropes in flexible rockfall barriers. The method is based on two full-scale model tests with an impact energy of 3000 kJ, as well as 36 set numerical models featuring varying lengths and impact energies. From the results of full scale tests and numerical models, it is inferred that the tension force at the end of the support rope is significantly less than that at the point of impact, exhibiting an approximate Gaussian attenuation distribution with propagation distance. To account for the attenuation of tensile forces in support ropes, a tensile attenuation coefficient is defined. Through comparative analysis of data obtained from 36 models with varying impact energies and propagation distances, the average attenuation coefficient for the upper support rope is determined to be approximately 0.7, while the average coefficient for the lower support rope is around 0.8. Utilizing the least squares method, a prediction method for the tension force of support ropes in flexible rockfall barriers is established. This method takes into account both the propagation distance and impact energy, enabling accurate predictions of the tensile behavior of the ropes under different conditions. This prediction model provides valuable insights for engineers in the design and optimization of these flexible barriers for rockfall mitigation.

Neutrophil lncRNA ZNF100-6:2 is a potential diagnostic marker for active pulmonary tuberculosis.

Active pulmonary tuberculosis (PTB) poses challenges in rapid diagnosis within complex clinical conditions. Given the close association between neutrophils and tuberculosis, we explored differentially expressed long non-coding RNAs (lncRNAs) in neutrophils as potential molecular markers for diagnosing active PTB. We employed a gene microarray to screen for lncRNA alterations in neutrophil samples from three patients with active PTB and three healthy controls. The results revealed differential expression of 1457 lncRNAs between the two groups, with 916 lncRNAs upregulated and 541 lncRNAs down-regulated in tuberculosis patients. Subsequent validation tests demonstrated down-regulation of lncRNA ZNF100-6:2 in patients with active PTB, which was restored following anti-tuberculosis treatment. Our findings further indicated a high diagnostic potential for lncRNA ZNF100-6:2, as evidenced by an area under the receiver operating characteristic (ROC) curve of 0.9796 (95% confidence interval: 0.9479 to 1.000; P < 0.0001). This study proposes lncRNA ZNF100-6:2 as a promising and novel diagnostic biomarker for active PTB.

Spontaneous multivessel coronary artery spasm: a case report.

A 60-year-old male presented to the emergency department of our hospital with persistent dull pain in the lower and middle sternum with generalized sweating after a heated argument with another person, and his symptoms did not resolve after 3 hours of onset.

Alterations in Serum Lipids and Lipoproteins Induced by Neoadjuvant Chemotherapy in Patients with Osteosarcoma around the Knee Joint: A Retrospective Analysis.

OBJECTIVE: To investigate the serum lipid profiles of patients with localized osteosarcoma around the knee joint before and after neoadjuvant chemotherapy. METHODS: After retrospectively screening the data of 742 patients between January 2007 and July 2020, 50 patients aged 13 to 39 years with Enneking stage II disease were included in the study. Serum lipid levels, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein-α [Lp(a)], and apolipoprotein A1, B, and E (ApoA1, ApoB, and ApoE), and clinicopathological characteristics were collected before and after neoadjuvant chemotherapy. RESULTS: The mean levels of TC, TG, and ApoB were significantly increased following neoadjuvant chemotherapy (16%, 38%, and 20%, respectively, vs. pretreatment values; P<0.01). The mean levels of LDL-C and ApoE were also 19% and 16% higher, respectively (P<0.05). No correlation was found between the pretreatment lipid profile and the histologic response to chemotherapy. An increase in Lp(a) was strongly correlated with the Ki-67 index (R=0.31, P=0.023). Moreover, a trend toward longer disease-free survival (DFS) was observed in patients with decreased TG and increased LDL-C following chemotherapy, although this difference was not statistically significant (P=0.23 and P=0.24, respectively). CONCLUSION: Significant elevations in serum lipids were observed after neoadjuvant chemotherapy in patients with localized osteosarcoma. There was no prognostic significance of pretreatment serum lipid levels on histologic response to neoadjuvant chemotherapy. The scale of increase in serum Lp(a) might have a potential prognostic role in osteosarcoma. Patients with increased LDL-C or reduced TG after chemotherapy seem to exhibit a trend toward favorable DFS.

Design and biophysical characterization of a monomeric four-alpha-helix bundle protein Aα4 with affinity for the volatile anesthetic halothane.

A monomeric four-α-helix bundle protein Aα4 was designed as a step towards investigating the interaction of volatile general anesthetics with their putative membrane protein targets. The alpha helices, connected by glycine loops, have the sequence A, B, B', A'. The DNA sequence was designed to make the helices with the same amino acid sequences (helix A and A', B and B', respectively) as different as possible, while using codons which are favorable for expression in E. coli. The protein was bacterially expressed and purified to homogeneity using reversed-phase HPLC. Protein identity was verified using MALDI-TOF mass spectrometry. Far-UV circular dichroism spectroscopy confirmed the predominantly alpha-helical nature of the protein Aα4. Guanidinium chloride induced denaturation showed that the monomeric four-α-helix bundle protein Aα4 is considerably more stable compared to the dimeric di-α-helical protein (Aα2-L38M)2. The sigmoidal character of the unfolding reaction is conserved while the sharpness of the transition is increased 1.8-fold. The monomeric four-α-helix bundle protein Aα4 bound halothane with a dissociation constant (K(d)) of 0.93 ± 0.02mM, as shown by both tryptophan fluorescence quenching and isothermal titration calorimetry. This monomeric four-α-helix bundle protein can now be used as a scaffold to incorporate natural central nervous system membrane protein sequences in order to examine general anesthetic interactions with putative targets in detail.

Role of poly(ADP-ribose) glycohydrolase in the regulation of cell fate in response to benzo(a)pyrene.

Poly(ADP-ribosyl)ation is a crucial regulator of cell fate in response to genotoxic stress. Poly(ADP-ribosyl)ation plays important roles in multiple cellular processes, including DNA repair, chromosomal stability, chromatin function, apoptosis, and transcriptional regulation. Poly(ADP-ribose) (PAR) degradation is carried out mainly by poly(ADP-ribose) glycohydrolase (PARG) enzymes. Benzo(a)pyrene (BaP) is a known human carcinogen. Previous studies in our laboratory demonstrated that exposure to BaP caused a concentration-dependent DNA damage in human bronchial epithelial (16HBE) cells. The role of PARG in the regulation of DNA damage induced by BaP is still unclear. To gain insight into the function of PARG and PAR in response to BaP, we used lentiviral gene silencing to generate 16HBE cell lines with stably suppressed PARG, and determined parameters of cell death and cell cycle following BaP exposure. We found that PARG was partially dependent on PAR synthesis, PARG depletion led to PAR accumulation. BaP-induced cell death was regulated by PARG, the absence of which was beneficial for undamaged cells. Our results further suggested that PARG probably has influence on ATM/p53 pathway and metabolic activation of BaP. Experimental evidences provided from this study suggest significant preventive properties of PAR accumulation in the toxicity caused by BaP.