Oxidative stress mediated decrement of spinal endomorphin-2 contributes to lumbar disc herniation sciatica in rats.

Increasing evidence supported that oxidative stress induced by herniated lumbar disc played important role in the formation of lumbar disc herniation sciatica (LDHS), however, the neural mechanisms underlying LDHS need further clarification. Endomorphin-2 (EM2) is the endogenous ligand for mu-opioid receptor (MOR), and there is increasing evidence implicating the involvement of spinal EM2 in neuropathic pain. In this study, using an nucleus pulposus implantation induced LDHS rat model that displayed obvious mechanical allodynia, it was found that the expression of EM2 in dorsal root ganglion (DRG) and spinal cord was significantly decreased. It was further found that oxidative stress in DRG and spinal cord was significantly increased in LDHS rats, and the reduction of EM2 in DRG and spinal cord was determined by oxidative stress dominated increment of dipeptidylpeptidase IV activity. A systemic treatment with antioxidant could prevent the forming of mechanical allodynia in LDHS rats. In addition, MOR expression in DRG and spinal cord remained unchanged in LDHS rats. Intrathecal injection of MOR antagonist promoted pain behavior in LDHS rats, and the analgesic effect of intrathecal injection of EM2 was stronger than that of endomorphin-1 and morphine. Taken together, our findings suggest that oxidative stress mediated decrement of EM2 in DRG and spinal cord causes the loss of endogenous analgesic effects and enhances the pain sensation of LDHS.

Single-cell analysis of a progressive Rosai-Dorfman disease affecting the cerebral parenchyma: a case report.

Neurologic Rosai-Dorfman disease (RDD) is a rare type of non-Langerhans cell histiocytosis that affects the central nervous system. Most neurologic RDDs grow like meningiomas, have clear boundaries, and can be completely resected. However, a few RDDs are invasive and aggressive, and no effective treatment options are available because the molecular mechanisms involved remain unknown. Here, we report a case of deadly and glucocorticoid-resistant neurologic RDD and explore its possible pathogenic mechanisms via single-cell RNA sequencing. First, we identified two distinct but evolutionarily related histiocyte subpopulations (the C1Q+ and SPP1+ histiocytes) that accumulated in the biopsy sample. The expression of genes in the KRAS signaling pathway was upregulated, indicating gain-of-function of KRAS mutations. The C1Q+ and SPP1+ histiocytes were highly differentiated and arrested in the G1 phase, excluding the idea that RDD is a lympho-histio-proliferative disorder. Second, although C1Q+ histiocytes were the primary RDD cell type, SPP1+ histiocytes highly expressed several severe inflammation-related and invasive factors, such as WNT5A, IL-6, and MMP12, suggesting that SPP1+ histiocytes plays a central role in driving the progression of this disease. Third, oligodendrocytes were found to be the prominent cell type that initiates RDD via MIF and may resist glucocorticoid treatment via the MDK and PTN signaling pathways. In summary, in this case, we report a rare presentation of neurologic RDD and provided new insight into the pathogenic mechanisms of progressive neurologic RDD. This study will also offer evidence for developing precision therapies targeting this complex disease.

Autophagy plays a pro-apoptotic role in arsenic trioxide-induced cell death of liver cancer.

OBJECTIVE: The effects of arsenic trioxide (As2O3) on hepatocellular carcinoma have been documented widely. Autophagy plays dual roles in the survival and death of cancer cells. Therefore, we investigated the exact role of autophagy in As2O3-induced apoptosis in liver cancer cells. METHODS: The viability of hepatoma cells was determined using the MTT assay with or without fetal bovine serum. The rate of apoptosis in liver cancer cells treated with As2O3 was evaluated using flow cytometry, Hoechst 33258 staining, and TUNEL assays. The rate of autophagy among liver cancer cells treated with As2O3 was detected using immunofluorescence, Western blot assay and transmission electron microscopy. RESULTS: Upon treatment with As2O3, the viability of HepG2 and SMMC-7721 cells was decreased in a time- and dose-dependent manner. The apoptosis rates of both liver cancer cell lines increased with the concentration of As2O3, as shown by flow cytometry. Apoptosis in liver cancer cells treated with As2O3 was also shown by the activation of the caspase cascade and the regulation of Bcl-2/Bax expression. Furthermore, As2O3 treatment induced autophagy in liver cancer cells; this finding was supported by Western blot, immunofluorescence of LC3-II and beclin 1, and transmission electron microscopy. In liver cancer cells, As2O3 inhibited the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signal pathway that plays a vital role in both apoptosis and autophagy. The PI3K activator SC-79 partially reversed As2O3-induced autophagy and apoptosis. Furthermore, inhibiting autophagy with 3-methyladenine partially reversed the negative effects of As2O3 on cell viability. Serum starvation increased autophagy and amplified the effect of As2O3 on cell death. CONCLUSION: As2O3 induces apoptosis and autophagy in liver cancer cells. Autophagy induced by As2O3 may have a proapoptotic effect that helps to reduce the viability of liver cancer cells. This study provides novel insights into the effects of As2O3 against liver cancer. Please cite this article as: Deng ZT, Liang SF, Huang GK, Wang YQ, Tu XY, Zhang YN, Li S, Liu T, Cheng BB. Autophagy plays a pro-apoptotic role in arsenic trioxide-induced cell death of liver cancer. J Integr Med. 2024; Epub ahead of print.

Study on mNGS Technique in Diagnosing Pneumocystis jirovecii Pneumonia in Non-HIV-Infected Patients.

Objective: To investigate the value of metagenomic Next-Generation Sequencing (mNGS) in diagnosing Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus (HIV)-infected patients. Methods: In this retrospective study, non-HIV-infected patients with PJP and those diagnosed with non-PJP from August 2022 to December 2024 were selected as subjects. The presence of Pneumocystis jirovecii (PJ) and other co-pathogens in bronchoalveolar lavage fluid (BALF) was analyzed, and the diagnostic efficacy of NGS, polymerase chain reaction (PCR) and serum 1,3-ß-D-glucan (BDG) in PJP was compared with the reference standard of clinical compound diagnosis. Results: Eighty-nine non-HIV-infected patients were recruited, with dyspnea as the primary symptom (69.66%) and solid malignant tumor as the most common underlying disease (20.22%). Taking clinical compound diagnosis as the reference standard, the sensitivity, specificity, negative predictive value and positive predictive value of mNGS were higher than those detected by PCR and serum BDG. Among 42 non-HIV-infected patients with PJP who underwent mNGS and conventional pathogen detection of BALF, 6 had simple PJ infection and 36 had combined PJ infection. The detection rate of mNGS in mixed infections was significantly higher than that of conventional pathogen detection (85.71 vs 61.70%, P = 0.012). A total of 127 pathogens were detected in BALF using mNGS, among which fungi had the highest detection rate (46.46%). The fungi, viruses and bacteria detected were mainly Pneumocystis jirovecii, human gammaherpesvirus 4 and Acinetobacter baumannii. Conclusion: mNGS is highly effective in diagnosing non-HIV-infected patients with PJP and exhibits ideal performance in the detection of co-pathogens. In addition, it has certain value for clinical diagnosis and guidance of targeted anti-infective drug treatment.

Antibacterial activity of lysozyme after association with carboxymethyl konjac glucomannan.

The unique high isoelectric point of lysozyme (LYZ) restricts its application in composite antibacterial coating due to the unfavorable liability to electrostatic interaction with other components. In this work, the antibacterial activity of a dispersible LYZ-carboxymethyl konjac glucomannan (CMKGM) polyelectrolyte complex was evaluated. Kinetic analysis revealed that, compared with free LYZ, the complexed enzyme exhibited decreased affinity (Km) but markedly increased Vmax against Micrococcus lysodeikticus, and QCM and dynamic light scattering analysis confirmed that the complex could bind with the substrate but in a much lower ratio. The complexation with CMKGM did not alter the antibacterial spectrum of LYZ, and the complex exerted antibacterial function by delaying the logarithmic growth phase and impairing the cell integrity of Staphylococcus aureus. Since the LYZ-CMKGM complex is dispersible in water and could be assembled easily, it has great potential as an edible coating in food preservation.

circular RNA circ-231 promotes protein biogenesis of TPI1 and PRDX6 through mediating the interaction of eIF4A3 with STAU1 to facilitate unwinding of secondary structure in 5' UTR, enhancing progression of human esophageal squamous cell carcinoma (ESCC).

Background: The nuclear cap-binding complex (CBC)-dependent translation (CT) is an important initial translation pathway for 5'-cap-dependent translation in normal mammal cells. Eukaryotic translation initiation factor 4A-III (eIF4A3), as an RNA helicase, is recruited to CT complex and enhances CT efficiency through participating in unwinding of secondary structure in the 5' UTR. However, the detailed mechanism for eIF4A3 implicated in unwinding of secondary structure in the 5' UTR in normal mammal cells is still unclear. Specially, we need to investigate whether the kind of mechanism in normal mammal cells extrapolates to cancer cells, e.g. ESCC, and further interrogate whether and how the mechanism triggers malignant phenotype of ESCC, which are important for identifying a potential therapeutic target for patients with ESCC. Methods: Bioinformatics analysis, RNA immunoprecipitation and RNA pulldown assays were performed to detect the interaction of circular RNA circ-231 with eIF4A3. In vitro and in vivo assays were performed to detect biological roles of circ-231 in ESCC. RNA immunoprecipitation, RNA pulldown, mass spectrometry analysis and co-immunoprecipitation assays were used to measure the interaction of circ-231, eIF4A3 and STAU1 in HEK293T and ESCC. In vitro EGFP reporter and 5' UTR of mRNA pulldown assays were performed to probe for the binding of circ-231, eIF4A3 and STAU1 to secondary structure of 5' UTR. Results: RNA immunoprecipitation assays showed that circ-231 interacted with eIF4A3 in HEK293T and ESCC. Further study confirmed that circ-231 orchestrated with eIF4A3 to control protein expression of TPI1 and PRDX6, but not for mRNA transcripts. The in-depth mechanism study uncovered that both circ-231 and eIF4A3 were involved in unwinding of secondary structure in 5' UTR of TPI1 and PRDX6. More importantly, circ-231 promoted the interaction between eIF4A3 and STAU1. Intriguingly, both circ-231 and eIF4A3 were dependent on STAU1 binding to secondary structure in 5' UTR. Biological function assays revealed that circ-231 promoted the migration and proliferation of ESCC via TPI1 and PRDX6. In ESCC, the up-regulated expression of circ-231 was observed and patients with ESCC characterized by higher expression of circ-231 have concurrent lymph node metastasis, compared with control. Conclusions: Our data unravels the detailed mechanism by which STAU1 binds to secondary structure in 5' UTR of mRNAs and recruits eIF4A3 through interacting with circ-231 and thereby eIF4A3 is implicated in unwinding of secondary structure, which is common to HEK293T and ESCC. However, importantly, our data reveals that circ-231 promotes migration and proliferation of ESCC and the up-regulated circ-231 greatly correlates with tumor lymph node metastasis, insinuating that circ-231 could be a therapeutic target and an indicator of risk of lymph node metastasis for patients with ESCC.

Combined effects of binary mixtures of 17ß-estradiol and testosterone in western mosquitofish (Gambusia affinis) after full life-cycle exposure.

Estrogens and androgens are typical steroid hormones and often occur together in contaminated aquatic environments, but their mixed effects in aquatic organisms have been less well reported. In this study, the endocrine disrupting effects of binary mixtures of 17ß-estradiol (E2) and testosterone (T) in western mosquitofish (Gambusia affinis) were assessed by analyzing the sex ratio, secondary sex characteristics, gonadal histology, and transcriptional expression of target genes related to the hypothalamic-pituitary-gonadal (HPG) axis in G. affinis (from embryos) continuously exposed to E2 (50 ng/L), T (T1: 50 ng/L; T2: 200 ng/L), and mixtures of both (E2 + T1: 50 + 50 ng/L; E2 + T2: 50 + 200 ng/L) for 119 d. The results showed that exposure to E2 + T1 and E2 + T2 reduced the length ratio of ray 4/6 ratio in male G. affinis, suggesting feminized phenomenon in male G. affinis. Furthermore, 16.7-38.5 % of female G. affinis showed masculinized anal fins and hemal spines when exposed to T alone and in combination with E2. Importantly, the transcriptional levels of certain target genes related to the HPG axis were significantly altered in G. affinis following exposure to E2 and T alone and in combinations. Moreover, exposure to E2 and T in combinations can lead to combined effects (such as synergistic and antagonistic effects) on the transcriptional levels of some genes. These results collectively suggest that exposure to environmentally relevant concentrations of E2 and T alone and in mixtures can impact the endocrine system of G. affinis, and may pose potential risks in aquatic systems.

Physical exercise frequency and cognition: a multicenter cross-sectional cohort study.

Background and aims: Dementia imposes a heavy burden on society and families, therefore, effective drug treatments, exploring and preventing factors associated with dementia, are paramount. To provide reference points for the best frequency of physical exercise (physical exercise), we investigated the association between frequency of PE and cognition in Chinese old adults. Methods: 16,181 Chinese participants aged 65 years or older were included in this study. Associations between PE and cognition were estimated multivariate logistic and linear regression analyses. Associations were further investigated across dementia subtypes (Alzheimer dementia, vascular dementia, and other types of dementia). Subgroup analyses were performed in different age groups, in populations with and without stroke, and those with and without hypertension. Results: PE associated with dementia after adjusting for full covariates (OR: 0.5414, 95% CI: 0.4536-0.6491, p < 0.001). Exercise performed at ≥3 times/week associated with lower risk of dementia (OR: 0.4794-0.6619, all p value <0.001). PE was associated with improved cognition (ß: 12851, p < 0.001), and any PE frequency contributed to cognitive improvement (p values for exercise performed ≥1 time/week were <0.001). Similar conclusions were identified when we repeated analyses in different dementia subtypes and age groups. Subgroup analyses suggested that the cognition of individuals without hypertension also benefitted from exercising 1-2 times/week (OR: 0.6168, 95% CI: 0.4379-0.8668, p = 0.005). Conclusion: The best exercise frequency is exercising ≥3 times/week for individuals from different dementia subtypes and age groups. While for those without hypertension, PE at 1-2 times /week is also beneficial.

Prevalence of aggressive care among patients with cancer near the end of life: a systematic review and meta-analysis.

Background: Aggressive care near patients' end-of-life (EOL) entails limited therapeutic values, high costs, and compromised quality of life (QoL). In this study, we aimed to estimate the global prevalence of aggressive care in patients with cancer and explore potential subgroup differences. Methods: We searched PubMed, Embase, and the Cochrane Library from database inception to Feb 16, 2024. Eligible studies reported the prevalence of aggressive EOL care using at least one quantifiable measure. Random-effects models were used to derive the pooled prevalence and subgroup analyses were performed to investigate differences in the prevalence of aggressive care across regions, the country's level of economic development, tumor types, ages, and sample sizes. This review is registered with PROSPERO, number CRD42023467839. Findings: A total of 129 studies were included in this systematic review, of which 118 (91.5%) were from high-income countries. Studies were mostly conducted in the Americas (60, 46.5%), Europe (34, 26.4%), and Western Pacific (31, 24.0%). Measures of aggressive care were inconsistent across studies, with the most commonly used measure being the use of chemotherapy in the last 14 days of life (DOLs) (n = 87, 67.4%) and intensive care unit (ICU) stay in the last 30 DOLs (n = 87, 67.4%). The prevalence of the five claims-based measures of aggressive care, i.e., chemotherapy in the last 14 DOLs, ICU stay in the last 30 DOLs, repeated hospital admission in the last 30 DOLs, repeated emergency room (ER) visit in the last 30 DOLs, and hospice care <3 days before death were 11.6% (95% CI, 9.8%-13.4%), 14.4% (95% CI, 11.8%-17.0%), 17.9% (95% CI, 14.4%-21.4%), 14.8% (95% CI, 12.0%-17.6%), and 14.4% (95% CI, 11.2%-17.6%), respectively. Regional differences were statistically significant in the prevalence of ICU stay and repeated hospital admission in the last 30 DOLs (p < 0.01; p = 0.03). Patients with hematologic malignancies were more likely to receive aggressive care than those with solid tumors, as seen in their higher rates of chemotherapy in the last 14 DOLs (21.7% versus 11.6%; p = 0.03), ICU stay in the last 30 DOLs (25.5% versus 10.8%; p < 0.01), and hospice care <3 days before death (26.7% versus 14.2%; p < 0.01). In addition, the prevalence of chemotherapy in the last 14 DOLs (26.2%; p < 0.01) and repeated hospital admission in the last 30 DOLs (31.4%; p < 0.01) were highest among pediatric patients with cancer. Interpretation: This meta-analysis found that aggressive EOL care was common in patients with cancer, regardless of the definition used, and varied by regions and populations. It is necessary to be aware of the global burden of aggressive care for patients with cancer near their EOL and take prompt action to address it. Funding: National Natural Science Foundation of China (Grant No. 72274004).

Nuclear transport of phosphorylated LanCL2 promotes invadopodia formation and tumor progression of glioblastoma by activating STAT3/Cortactin signaling.

INTRODUCTION: Our previous study showed that the abscisic acid receptor lanthionine synthetase C-like 2 (LanCL2) is a significant prognostic factor for overall survival in young glioblastoma patients. However, the role of LanCL2 in glioblastoma remains unclear yet. OBJECTIVES: This study aims to investigate the role of LanCL2 in regulating in-vitro cell invasion and in-vivo tumor progression of glioblastoma and its underlying mechanism. METHODS: Tyrosine 198 or 295 residue of LanCL2 was mutated using site-directed mutagenesis to block its phosphorylation. The role of LanCL2 in glioblastoma was investigated using transwell or 3D invasion assay, matrix degradation assay and intracranial xenograft model. RESULTS: This study showed that nuclear transport of LanCL2 was enhanced by overexpression of LanCL2 or its ligand abscisic acid in glioblastoma cells. Knockdown of LanCL2 suppressed migration, invasion and invadopodia formation of glioblastoma cells, whereas overexpression of wild-type LanCL2 enhanced them. Blocking of Tyr295 residue phosphorylation of LanCL2 impeded its nuclear transport, retarded glioblastoma cell motility and invadopodia formation, and deceased the phosphorylation of Cortactin and STAT3. c-Met was identified as the upstream tyrosine kinase of Tyr295 residue of LanCL2, and inhibition of c-Met markedly suppressed the nuclear transport of LanCL2. Moreover, overexpression of wild-type LanCL2 significantly promoted orthotopic tumor growth of glioblastoma in vivo and led to poor survival of mice with median survival time of 33.5 days, whereas Tyr295 mutation rescued it with median survival time of 49 days. CONCLUSION: Our findings suggested that Tyr295 phosphorylation is crucial to the activation and nuclear transport of LanCL2, as well as invadopodia formation and tumor progression of glioblastoma, providing the evidence of a novel signaling axis c-Met/LanCL2/STAT3/Cortactin and the first observation of the importance of Tyr295 phosphorylation to LanCL2.

Novel PLCZ1 mutation caused polyspermy during in vitro fertilization.

ABSTRACT: Failure of oocyte activation, including polyspermy and defects in pronuclear (PN) formation, triggers early embryonic developmental arrest. Many studies have shown that phospholipase C zeta 1 ( PLCZ1 ) mutations cause failure of PN formation following intracytoplasmic sperm injection (ICSI); however, whether PLCZ1 mutation is associated with polyspermy during in vitro fertilization (IVF) remains unknown. Whole-exome sequencing (WES) was performed to identify candidate mutations in couples with primary infertility. Sanger sequencing was used to validate the mutations. Multiple PLCZ1 -mutated sperm were injected into human and mouse oocytes to explore whether PN formation was induced. Assisted oocyte activation (AOA) after ICSI was performed to overcome the failure of oocyte activation. We identified three PLCZ1 mutations in three patients who experienced polyspermy during IVF cycles, including a novel missense mutation c.1154C>T, p.R385Q. PN formation failure was observed during the ICSI cycle. However, injection of multiple PLCZ1 -mutated sperm induced PN formation, suggesting that the Ca 2+ oscillations induced by the sperm exceeded the necessary threshold for PN formation. AOA after ICSI enabled normal fertilization, and all patients achieved successful pregnancies. These findings expand the mutational spectrum of PLCZ1 and suggest an important role for PLCZ1 in terms of blocking polyspermy. Furthermore, this study may benefit genetic diagnoses in cases of abnormal fertilization and provide potential appropriate therapeutic measures for these patients with sperm-derived polyspermy.

CdBi2S4-Decorated Aminated Polyacrylonitrile Nanofiber for Photocatalytic Treatment of Cr(VI) and Tetracycline Wastewater.

The significant threat posed by the high toxicity of heavy metals and antibiotics in water pollutants has prompted a growing emphasis on the development of highly efficient removal methods for these pollutants. In this paper, flexible electrospinning polyacrylonitrile (PAN) nanofiber-supported CdBi2S4 was synthesized via a hydrothermal method, followed by amination treatment with diethylenetriamine (DETA). The as-prepared CdBi2S4/NH2-PAN nanofiber, enriched with sulfur vacancies, demonstrated outstanding visible-light trapping ability and a suitable band gap, leading to efficient separation and transport of photogenerated carriers, ultimately resulting in exceptional photocatalytic capability. The optimal 3-CdBi2S4/NH2-PAN nanofiber achieved impressive reduction rates of 92.26% for Cr(VI) and 96.45% for tetracycline hydrochloride (TCH) within 120 min, which were much higher than those for CdS/NH2-PAN, Bi2S3/NH2-PAN, and CdBi2S4/PAN nanofibers. After five cycles, the removal rate of the CdBi2S4/NH2-PAN nanofiber consistently remained above 90%. Their ease of separation and recovery from the application environment contributes to their practicality. Additionally, compared with conventional suspended particle catalyzers, the composite nanofiber exhibited remarkable flexibility and self-supporting properties.

Synthesis of gem-Difluoro-3,4-dihydro-2H-pyrans via a TfOH-Catalyzed [4 + 2] Annulation of Difluoroenoxysilanes with α-Cyano Chalcones.

Difluoroenoxysilane, a commonly used difluoroallylating reagent, has attracted considerable attention in recent years. However, its application in the annulation reaction for the construction of fluorinated heterocyclic compounds remains relatively limited. Presented here is the Brønsted acid-catalyzed efficient formal [4 + 2] annulation of difluoroenoxysilanes with α-cyano chalcones. The developed protocol demonstrates tolerance to various substituents under mild reaction conditions, providing a reliable approach to construct gem-difluoro-3,4-dihydro-2H-pyrans in good to excellent yields with high diastereoselectivities.

Interaction of 17α-ethinylestradiol and methyltestosterone in western mosquitofish (Gambusia affinis) across two generations.

The interactions between estrogen and androgen in aquatic animals remain largely unknown. In this study, two generations (F0 and F1) of western mosquitofish (Gambusia affinis) were continuously exposed to 17α-ethinylestradiol (EE2, 10 ng/L), methyltestosterone (MT, 10 ng/L (MTL); 50 ng/L (MTH)), and mixtures (EE2+MTL and EE2+MTH). Various endpoints, including sex ratio (phenotypic and genetic), secondary sex characteristics, gonadal histology, and transcriptional profile of genes, were examined. The results showed that G. affinis exposed to MTH and EE2+MTH had a > 89.7 % of phenotypic males in F1 generation, with 34.5 and 50.0 % of these males originated from genetic females, respectively. Moreover, females from F0 and F1 generations exposed to MTH and EE2+MTH exhibited masculinized anal fins and skeletons. The combined effect of MT and EE2 on most endpoints was dependent on MT. Furthermore, significant transcriptional alterations in certain target genes were observed in both the F0 and F1 generations by EE2 and MT alone and by mixtures, showing some degree of interactions. These findings that the effects of EE2+MTH were primarily on the phenotypic sex of G. affinis in offspring generation suggest that G. affinis under chronic exposure to the binary mixture contaminated water could have sex-biased populations.

Essential contribution of the JAK/STAT pathway to carcinogenesis, lytic infection of herpesviruses and pathogenesis of COVID­19 (Review).

The intracellular pathway of Janus kinase/signal transducer and activator of transcription (JAK/STAT) and modification of nucleosome histone marks regulate the expression of proinflammatory mediators, playing an essential role in carcinogenesis, antiviral immunity and the interaction of host proteins with Herpesviral particles. The pathway has also been suggested to play a vital role in the clinical course of the acute infection caused by severe acute respiratory syndrome coronavirus type 2 (SARS­CoV­2; known as coronavirus infection­2019), a novel human coronavirus initially identified in the central Chinese city Wuhan towards the end of 2019, which evolved into a pandemic affecting nearly two million people worldwide. The infection mainly manifests as fever, cough, myalgia and pulmonary involvement, while it also attacks multiple viscera, such as the liver. The pathogenesis is characterized by a cytokine storm, with an overproduction of proinflammatory mediators. Innate and adaptive host immunity against the viral pathogen is exerted by various effectors and is regulated by different signaling pathways notably the JAK/STAT. The elucidation of the underlying mechanism of the regulation of mediating factors expressed in the viral infection would assist diagnosis and antiviral targeting therapy, which will help overcome the infection caused by SARS­CoV­2.

Highly Emissive and Robust Cd-Based MOF with an Unprecedented Topology for Tetracycline Sensing.

Herein, an unprecedented cadmium-based metal-organic framework (JNU-106) fabricated by utilizing pyrazole-functionalized tetraphenylethylene ligands (Py-TPE) and rod-shaped secondary building units is reported, possessing a new (3,3,3,6,6,8)-connected topological network. Thanks to the ingeniously designed intramolecular charge transfer behavior, which originates from the congruent coplanarity between Py and TPE, JNU-106 exhibits intense green luminescence with a quantum yield increased by 1.5 times. The phenomenon of remarkable fluorescence quenching of JNU-106 reveals that it possesses extremely high anti-interference performance, superior sensitivity, and dedicated selectivity toward tetracycline antibiotics (TCAs) in aqueous solutions, which are comparable to those of the state-of-the-art porous sensing compounds. Taking the theoretical calculations and experimental results into account, the luminescence quenching is mainly attributed to the internal filtration effect and the static quenching effect. Considering the portable and rapid performance of JNU-106-based testing strips for sensing TCAs, the fabricated JNU-106 provides an alternative for ecological monitoring and environmental governance.

Value of CT in targeted CT-guided epidural blood patching: Predictors for successful epidural punctures.

BACKGROUND AND PURPOSE: Differentiating epidural from intrathecal punctures before computed tomography (CT)-guided epidural blood patching (EBP) is subjective, relying on operator experience. This study aimed to investigate CT findings for epidural and intrathecal punctures and identify reliable predictors for successful epidural punctures before targeted CT-guided EBP. MATERIALS AND METHODS: We included 65 patients with low-cerebrospinal fluid (CSF)-pressure headache receiving targeted CT-guided EBP between January 2021 and October 2022 in this retrospective study. We analyzed clinical data, technical information, and CT features before EBP. Fisher's exact test was used for discrete variables, while Mann-Whitney U test was used for continuous variables. Positive (PLR) and negative likelihood ratios (NLR) were calculated to identify predictors for confirming epidural punctures. RESULTS: We confirmed 43 patients as epidural punctures and 22 patients as intrathecal punctures. Before contrast injection, epidural fat at the needle tip in the epidural group was higher than the intrathecal group (37.2 % [16/43] vs. 4.5 % [1/22], p = 0.006). After contrast injection, the "contrast-needle tip connection" sign was mostly observed in the epidural group than the intrathecal group (95.3 % [41/43] vs. 9.1 % [2/22], p < 0.001). Additionally, the epidural group had significantly higher boomerang-shaped contrast morphology than the intrathecal group (65.1 % [28/43] vs. 9.1 % [2/22], p < 0.001). The "contrast-needle tip connection" sign had the highest PLR (10.49) and lowest NLR (0.05). CONCLUSION: Identifying epidural fat at the needle tip, "contrast-needle tip connection" sign, and boomerang-shaped contrast morphology on CT scans are useful for confirming proper placement of the needle tip within the epidural space.

Usefulness of cone-beam computed tomography-reformatted epidurography in percutaneous epidural adhesiolysis: A pilot study.

BACKGROUND: Conventional epidurography (CE) is thought to have insufficient usefulness on percutaneous epidural adhesiolysis (PEA). We aimed to evaluate the association between the outcome of PEA and cone-beam computed tomography-reformatted epidurography (CBCT-RE). METHODS: After ethics board approval and written informed consent were obtained, we performed 30 PEA in 26 participants, and evaluated their post-PEA image findings. Two independent radiologists categorized and recorded the occurrence of contrast in the intracanal ventral and extraforaminal regions on CE, and in the dorsal canal (DC), ventral canal (VC), dorsal foramen (DF), and ventral foramen (VF) on CBCT-RE. Reproducibility was assessed using intraclass correlation coefficients (ICCs). Baseline characteristics along with contrast distribution patterns of CE and CBCT-RE were analyzed in terms of their association with symptom relief at 1 month after PEA. RESULTS: The rate of patients with symptoms relief >50% after PEA was 63.3%. The inter-reader agreement was higher for CBCT-RE (ICC = 0.955) than for CE (ICC = 0.793). Participants with contrast coexisting in VC and DF adjacent to the irritated nerve root on CBCT-RE ( p = 0.015) had a significantly better response after PEA than those without contrast at these locations on CBCT-RE, independent of baseline characteristics (adjusted odds ratio: 11.414 [ p = 0.012]). CONCLUSION: CBCT-RE with identifying contrast distribution patterns is useful for predicting outcome of PEA.