Alteration of replication protein A binding mode on single-stranded DNA by NSMF potentiates RPA phosphorylation by ATR kinase.

Replication protein A (RPA), a eukaryotic single-stranded DNA (ssDNA) binding protein, dynamically interacts with ssDNA in different binding modes and plays essential roles in DNA metabolism such as replication, repair, and recombination. RPA accumulation on ssDNA due to replication stress triggers the DNA damage response (DDR) by activating the ataxia telangiectasia and RAD3-related (ATR) kinase, which phosphorylates itself and downstream DDR factors, including RPA. We recently reported that the N-methyl-D-aspartate receptor synaptonuclear signaling and neuronal migration factor (NSMF), a neuronal protein associated with Kallmann syndrome, promotes RPA32 phosphorylation via ATR upon replication stress. However, how NSMF enhances ATR-mediated RPA32 phosphorylation remains elusive. Here, we demonstrate that NSMF colocalizes and physically interacts with RPA at DNA damage sites in vivo and in vitro. Using purified RPA and NSMF in biochemical and single-molecule assays, we find that NSMF selectively displaces RPA in the more weakly bound 8- and 20-nucleotide binding modes from ssDNA, allowing the retention of more stable RPA molecules in the 30-nt binding mode. The 30-nt binding mode of RPA enhances RPA32 phosphorylation by ATR, and phosphorylated RPA becomes stabilized on ssDNA. Our findings provide new mechanistic insight into how NSMF facilitates the role of RPA in the ATR pathway.

Holistic immunomodulation for small cell lung cancer.

Small cell lung cancer (SCLC) is characterized by a high mortality rate, rapid growth, and early metastasis, which lead to a poor prognosis. Moreover, limited clinical treatment options further lower the survival rate of patients. Therefore, novel technology and agents are urgently required to enhance clinical efficacy. In this review, from a holistic perspective, we summarized the therapeutic targets, agents and strategies with the most potential for treating SCLC, including chimeric antigen receptor (CAR) T therapy, immunomodulating antibodies, traditional Chinese medicines (TCMs), and the microbiota, which have been found recently to improve the clinical outcomes and prognosis of SCLC. Multiomics technologies can be integrated to develop effective diagnostic methods and identify new targets for new drug discovery in SCLC. We discussed in depth the feasibility, potential, and challenges of these new strategies, as well as their combinational treatments, which may provide promising alternatives for enhancing the clinical efficacy of SCLC in the future.

Dual Immunoglobulin Domain-Containing Cell Adhesion Molecule Increases Early in Renal Tubular Cell Injury and Plays Anti-Inflammatory Role.

Dual immunoglobulin domain-containing cell adhesion molecule (DICAM) is a type I transmembrane protein that presents in various cells including renal tubular cells. This study evaluated the expression and protective role of DICAM in renal tubular cell injury. HK-2 cells were incubated and treated with lipopolysaccharide (LPS, 30 µg/mL) or hydrogen peroxide (H2O2, 100 µM) for 24 h. To investigate the effect of the gene silencing of DICAM, small interfering RNA of DICAM was used. Additionally, to explain its role in cellular response to injury, DICAM was overexpressed using an adenoviral vector. DICAM protein expression levels significantly increased following treatment with LPS or H2O2 in HK-2 cells. In response to oxidative stress, DICAM showed an earlier increase (2-4 h following treatment) than neutrophil gelatinase-associated lipocalin (NGAL) (24 h following treatment). DICAM gene silencing increased the protein expression of inflammation-related markers, including IL-1ß, TNF-α, NOX4, integrin ß1, and integrin ß3, in H2O2-induced HK-2 cell injury. Likewise, in the LPS-induced HK-2 cell injury, DICAM knockdown led to a decrease in occludin levels and an increase in integrin ß3, IL-1ß, and IL-6 levels. Furthermore, DICAM overexpression followed by LPS-induced HK-2 cell injury resulted in an increase in occludin levels and a decrease in integrin ß1, integrin ß3, TNF-α, IL-1ß, and IL-6 levels, suggesting an alleviating effect on inflammatory responses. DICAM was elevated in the early stage of regular tubular cell injury and may protect against renal tubular injury through its anti-inflammatory properties. DICAM has a potential as an early diagnostic marker and therapeutic target for renal cell injury.

Nanoarchitectonics of MXene Derived TiO2 /Graphene with Vertical Alignment for Achieving the Enhanced Supercapacitor Performance.

Structural engineering and hybridization of heterogeneous 2D materials can be effective for advanced supercapacitor. Furthermore, architectural design of electrodes particularly with vertical construction of structurally anisotropic graphene nanosheets, can significantly enhance the electrochemical performance. Herein, MXene-derived TiO2 nanocomposites hybridized with vertical graphene is synthesized via CO2 laser irradiation on MXene/graphene oxide nanocomposite film. Instantaneous photon energy by laser irradiation enables the formation of vertical graphene structures on nanocomposite films, presenting the controlled anisotropy in free-standing film. This vertical structure enables improved supercapacitor performance by forming an open structure, increasing the electrolyte-electrode interface, and creating efficient electron transport path. In addition, the effective oxidation of MXene nanosheets by instantaneous photon energy leads to the formation of rutile TiO2 . TiO2 nanoparticles directly generated on graphene enables the effective current path, which compensates for the low conductivity of TiO2 and enables the functioning of an effective supercapacitor by utilizing its pseudocapacitive properties. The resulting film exhibits excellent specific areal capacitance of 662.9 mF cm-2 at a current density of 5 mA cm-2 . The film also shows superb cyclic stability during 40 000 repeating cycles, maintaining high capacitance. Also, the pseudocapacitive redox reaction kinetics is evaluated, showing fast redox kinetics with potential for high-performance supercapacitor applications.

PWWP2B promotes DNA end resection and homologous recombination.

Genome instability is one of the leading causes of gastric cancers. However, the mutational landscape of driver genes in gastric cancer is poorly understood. Here, we investigate somatic mutations in 25 Korean gastric adenocarcinoma patients using whole-exome sequencing and show that PWWP2B is one of the most frequently mutated genes. PWWP2B mutation correlates with lower cancer patient survival. We find that PWWP2B has a role in DNA double-strand break repair. As a nuclear protein, PWWP2B moves to sites of DNA damage through its interaction with UHRF1. Depletion of PWWP2B enhances cellular sensitivity to ionizing radiation (IR) and impairs IR-induced foci formation of RAD51. PWWP2B interacts with MRE11 and participates in homologous recombination via promoting DNA end-resection. Taken together, our data show that PWWP2B facilitates the recruitment of DNA repair machinery to sites of DNA damage and promotes HR-mediated DNA double-strand break repair. Impaired PWWP2B function might thus cause genome instability and promote gastric cancer development.

Impact of Everolimus Initiation and Corticosteroid Weaning During Acute Phase After Heart Transplantation on Clinical Outcome: Data from the Korean Organ Transplant Registry (KOTRY).

The effect of changes in immunosuppressive therapy during the acute phase post-heart transplantation (HTx) on clinical outcomes remains unclear. This study aimed to investigate the effects of changes in immunosuppressive therapy by corticosteroid (CS) weaning and everolimus (EVR) initiation during the first year post-HTx on clinical outcomes. We analyzed 622 recipients registered in the Korean Organ Transplant Registry (KOTRY) between January 2014 and December 2021. The median age at HTx was 56 years (interquartile range [IQR], 45-62), and the median follow-up time was 3.9 years (IQR 2.0-5.1). The early EVR initiation within the first year post-HTx and maintenance during the follow-up is associated with reduced the risk of primary composite outcome (all-cause mortality or re-transplantation) (HR, 0.24; 95% CI 0.09-0.68; p < 0.001) and cardiac allograft vasculopathy (CAV) (HR, 0.39; 95% CI 0.19-0.79; p = 0.009) compared with EVR-free or EVR intermittent treatment regimen, regardless of CS weaning. However, the early EVR initiation tends to increase the risk of acute allograft rejection compared with EVR-free or EVR intermittent treatment.

Previously Uncharacterized Variants, OCF-E-OCF-J, of the Antifungal Occidiofungin Produced by Burkholderia contaminans MS14.

The rise of multidrug resistant fungal infections highlights the need to identify and develop novel antifungal agents. Occidiofungin is a nonribosomally synthesized glycolipopeptide that has a unique mechanism of action, disrupting actin-mediated functions and inducing cellular apoptosis. Antifungal activity has been observed in vitro against various fungal species, including multidrug resistant Candida auris, and in vivo efficacy has been demonstrated in a murine vulvovaginal candidiasis model. Occidiofungin, a cyclic glycolipopeptide, is composed of eight amino acids and in previous studies, an asparagine residue was assigned at position 7 (ASN7). In this study, new structural variants of occidiofungin have been characterized which have aspartic acid (ASP7), glutamine (GLN7), or glutamic acid (GLU7) at position 7. The side chain of the ASP7 variant contains the only terminal carboxylic acid in the peptide and provides a useful site for selective chemical modifications. Analogues were synthesized at the ASP7 position and tested for antifungal activity. These analogues were shown to be more active as compared to the ASP7 variant against a panel of Candida species. The naturally occurring variants of occidiofungin with a side chain containing a carboxylic acid at the seventh amino acid position can be used to develop semisynthetic analogues with enhanced therapeutic properties.

Fe(III) Docking-Activated Sites in Layered Birnessite for Efficient Water Oxidation.

Non-noble metal catalysts for promoting the sluggish kinetics of oxygen evolution reaction (OER) are essential to efficient water splitting for sustainable hydrogen production. Birnessite has a local atomic structure similar to that of an oxygen-evolving complex in photosystem II, while the catalytic activity of birnessite is far from satisfactory. Herein, we report a novel Fe-Birnessite (Fe-Bir) catalyst obtained by controlled Fe(III) intercalation- and docking-induced layer reconstruction. The reconstruction dramatically lowers the OER overpotential to 240 mV at 10 mA/cm2 and the Tafel slope to 33 mV/dec, making Fe-Bir the best of all the reported Bir-based catalysts, even on par with the best transition-metal-based OER catalysts. Experimental characterizations and molecular dynamics simulations elucidate that the catalyst features active Fe(III)-O-Mn(III) centers interfaced with ordered water molecules between neighboring layers, which lower reorganization energy and accelerate electron transfer. DFT calculations and kinetic measurements show non-concerted PCET steps conforming to a new OER mechanism, wherein the neighboring Fe(III) and Mn(III) synergistically co-adsorb OH* and O* intermediates with a substantially reduced O-O coupling activation energy. This work highlights the importance of elaborately engineering the confined interlayer environment of birnessite and more generally, layered materials, for efficient energy conversion catalysis.

Therapeutic Effects of Aloe saponaria against Ulcerative Colitis Induced by Dextran Sulfate Sodium.

Aloe vera (A. vera) has been studied as a treatment option for ulcerative colitis (UC), but there is a lack of scientific evidence showing whether treatment with Aloe saponaria (A. saponaria) can also be beneficial. To investigate the therapeutic potential of A. saponaria as a treatment for UC, clinical symptoms, histopathological characteristics of the colon, inflammatory response, and toxicity were analyzed in dextran sulfate sodium (DSS)-induced UC mice after administration of aqueous extracts of A. saponaria (AAS) for 7 days. The total polyphenol and tannin content of AAS was 272 µg/g and 163 µg/g, respectively. AAS exhibited significant antioxidant activity. Several clinical symptoms, including body weight, colon length, and hematochezia, remarkably improved in the DSS+AAS treated group compared to the DSS+Vehicle-treated group. In addition, similar improvements were detected in the histopathological characteristics and mucin-secreting ability in the colon of DSS-induced UC mice after the administration of AAS. The levels of infiltrated inflammatory cells and cytokine expression were significantly decreased in a dose-dependent manner in the colon of the DSS+AAS-treated group. These alterations in inflammatory response were accompanied by a significant recovery of the protein kinase C/extracellular signal-regulated kinase (PKC/ERK) and phosphatidylinositol-3-kinase/serine-threonine protein kinase (PI3K/Akt) signaling pathways. However, the levels of key markers for hepatotoxicity and nephrotoxicity consistently remained between those of the DSS+AAS-treated and the No groups. Therefore, the results of the present study provide novel evidence that AAS may improve the clinical symptoms and attenuate the inflammatory response in DSS-induced UC mice and does not have any significant hepatotoxicity or nephrotoxicity.

CERS4 predicts positive anti-PD-1 response and promotes immunomodulation through Rhob-mediated suppression of CD8+Tim3+ exhausted T cells in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the main malignant tumors with high mortality and short survival time. Immunotherapy has become the standard treatment for advanced NSCLC, but it has the problems of drug resistance and low response rate. Therefore, obtaining effective biomarkers to predict and enhance immune checkpoint inhibitors (ICIs) efficacy in NSCLC is important. Sphingolipid metabolism is recently found to be closely involved in tumor immunotherapy. CERS4, an important sphingolipid metabolizing enzyme, is positively correlated with the efficacy of anti-PD-1 therapy for NSCLC. Upregulation of CERS4 expression could improve the efficacy of anti-PD-1 therapy for NSCLC. High expression of CERS4 could downregulate the expression of Rhob in tumor. Significantly, the ratio of CD4+/CD8+ T cell increased and the ratio of Tim-3+/CD8+ T cell decreased in spleen and peripheral blood cells. When Rhob was knocked out, the efficacy of PD-1 mAb treatment increased, and the frequency of Tim-3+ CD8+ T cell decreased. This finding further confirmed the role of sphingolipid metabolites in regulating the immunotherapeutic function of NSCLC. These metabolites may improve the efficacy of PD-1 mAb in NSCLC by regulating the CERS4/Rhob/Tim-3 axis. Overall, this study provided a potential and effective target for predicting and improving the efficacy of ICIs for NSCLC. It also provided a new perspective for the study on the mechanisms of ICIs resistance for NSCLC.

ß-Elemene enhances erlotinib sensitivity through induction of ferroptosis by upregulating lncRNA H19 in EGFR-mutant non-small cell lung cancer.

Nearly half of all Asian non-small cell lung cancer (NSCLC) patients harbour epidermal growth factor receptor (EGFR) mutations, and first-generation EGFR tyrosine kinase inhibitors (TKIs) are one of the first-line treatments that have improved the outcomes of these patients. Unfortunately, 20% of these patients can not benefit from the treatment. The basis of this primary resistance is poorly understood. Therefore, overcoming EGFR-TKI primary resistance and maintaining the efficacy of TKIs has become a key issue. ß-Elemene, a sesquiterpene compound extracted from Curcuma aromatica Salisb. (wenyujing), has shown potent antitumor effects. In this research, we found that ß-elemene combined with erlotinib enhanced the cytotoxicity of erlotinib to primary EGFR-TKI-resistant NSCLC cells with EGFR mutations and that ferroptosis was involved in the antitumor effect of the combination treatment. We found that lncRNA H19 was significantly downregulated in primary EGFR-TKI-resistant NSCLC cell lines and was upregulated by the combination treatment. Overexpression or knockdown of H19 conferred sensitivity or resistance to erlotinib, respectively, in both in vitro and in vivo studies. The high level of H19 enhanced the cytotoxicity of erlotinib by inducing ferroptosis. In conclusion, our data showed that ß-elemene combined with erlotinib could enhance sensitivity to EGFR-TKIs through induction of ferroptosis via H19 in primary EGFR-TKI-resistant lung cancer, providing a promising strategy to overcome EGFR-TKI resistance in NSCLC patients.

Intraprocedural, Intra-Arterial CT Foot Perfusion Examination for Assessment of Endovascular Therapy in Patients With Critical Limb Ischemia: A Prospective Pilot Study.

BACKGROUND: Current techniques to evaluate computed tomography (CT) foot perfusion in patients with critical limb ischemia use high contrast doses and cannot be used during endovascular procedures. CT perfusion of the foot with intra-arterial contrast injection during endovascular treatment in a hybrid angiography CT suite might solve these problems. PURPOSE: The main objective of this study was to evaluate whether intra-arterial CT foot perfusion using a hybrid CT angiosystem is feasible during endovascular treatment for critical limb ischemia. MATERIAL AND METHODS: This prospective pilot study investigated intraprocedural, intra-arterial CT perfusion of the foot using a hybrid CT angiosystem in 12 patients before and after endovascular treatment for critical limb ischemia. Time to peak (TTP) and arterial blood flow were measured before and after treatment and compared using a paired t test. RESULTS: All 24 CT perfusion maps could be calculated adequately. The contrast volume used for one perfusion CT scan was 4.8 ml. The mean TTP before treatment was 12.8 seconds (standard deviation [SD] 2.8) and the mean TTP posttreatment was 8.4 seconds (SD 1.7), this difference being statistically significant (p=.001). Tendency toward increased blood flow after treatment, 340 ml/min/100 ml (SD 174) vs 514 ml/min/100 ml (SD 366) was noticed (p=.104). The mean effective radiation dose was 0.145 mSv per scan. CONCLUSION: Computed tomography perfusion of the foot with low contrast dose intra-arterial contrast injection during endovascular treatment in a hybrid angiography CT suite is a feasible technique. CLINICAL IMPACT: Intra-arterial CT foot perfusion using a hybrid CT-angiography system is a feasible new technique during endovascular therapy for critical limb ischemia to assess the results of the treament. Future research is necessary in defining endpoints of endovascular treatment and establishing its role in limb salvage prognostication.

NSMF promotes the replication stress-induced DNA damage response for genome maintenance.

Proper activation of DNA repair pathways in response to DNA replication stress is critical for maintaining genomic integrity. Due to the complex nature of the replication fork (RF), problems at the RF require multiple proteins, some of which remain unidentified, for resolution. In this study, we identified the N-methyl-D-aspartate receptor synaptonuclear signaling and neuronal migration factor (NSMF) as a key replication stress response factor that is important for ataxia telangiectasia and Rad3-related protein (ATR) activation. NSMF localizes rapidly to stalled RFs and acts as a scaffold to modulate replication protein A (RPA) complex formation with cell division cycle 5-like (CDC5L) and ATR/ATR-interacting protein (ATRIP). Depletion of NSMF compromised phosphorylation and ubiquitination of RPA2 and the ATR signaling cascade, resulting in genomic instability at RFs under DNA replication stress. Consistently, NSMF knockout mice exhibited increased genomic instability and hypersensitivity to genotoxic stress. NSMF deficiency in human and mouse cells also caused increased chromosomal instability. Collectively, these findings demonstrate that NSMF regulates the ATR pathway and the replication stress response network for genome maintenance and cell survival.

Exposures to humidifier disinfectant and various health conditions in Korean based on personal exposure assessment data of claimants for compensation.

BACKGROUND: Humidifier disinfectants (HDs) were commonly used household chemicals to prevent microbial growth in a humidifier water tank in South Korea. A growing body of evidence has indicated that its airborne exposure can induce severe lung injury. However, there has been low awareness of other health outcomes in HD users. This study aimed to evaluate health conditions appealed by claimants for compensation in relation with an increased exposure to HD. METHODS: From survey data of personal HD exposure assessment of claimants for compensation in Korea, we included a total of 4,179 subjects [cases in each dataset were defined by nine reported health conditions, i.e., pneumonia, asthma, cardiovascular disease, respiratory disease, otorhinolaryngologic disease, brain disease (including cerebrovascular disease), dermatological disease, lung cancer, and all cancers]. HD exposures was considered as the following exposure criteria: exposure duration, exposure proximity, exposure direction, chemical type, cumulative exposure time, indoor air concentration, and cumulative exposure level. Logistic regression models were used to evaluate the associations between HD exposure and health conditions. RESULTS: After adjusting for sociodemographic and health behavioral factors and other chemical exposures (households, environmental, and occupational exposures), an increase in cumulative HD exposure time was significantly associated with risks of all nine diseases (all p-trends < 0.05). An increase in HD exposure duration was associated with asthma, respiratory disease, otorhinolaryngologic disease, dermatological disease, all cancers, and lung cancer (p-trends < 0.05). Indoor HD concentration was associated with only pneumonia (p-trend = 0.015). CONCLUSIONS: Our findings suggest that cumulative exposures to airborne HD might potentially increase the risk of various reported health outcomes.

Proxalutamide for the treatment of COVID-19 rebound following Paxlovid treatment: Report of four cases and review of the literature.

BACKGROUND: The pandemic the coronavirus disease 2019 (COVID-19) has created a global health crisis. Although Paxlovid is recommended for the early-stage treatment of mild-to-moderate COVID-19 in patients at increased risk of progression to severe COVID-19, more and more cases are reported a COVID-19 rebound after Paxlovid treatment. Currently, information on the additional treatment for COVID-19 rebound following Paxlovid treatment is limited. CASE REPORT: Here, we present four cases with COVID-19 who were mild on admission. All cases experienced a COVID-19 rebound and progressed to severe COVID-19, following treatment with Paxlovid (300 mg of nirmatrelvir with 100 mg ritonavir, twice daily for 5 days). After being treated with proxalutamide (300 mg/day), all cases finally turned real-time reverse transcription polymerase chain reaction (RT-PCR) negative. CONCLUSION: Our cases suggested that proxalutamide might be an effective remedial treatment option for patients experiencing a COVID-19 rebound after Paxlovid treatment.

Complete encapsulation of sulfur through interfacial energy control of sulfur solutions for high-performance Li-S batteries.

Complete encapsulation of high-content sulfur in porous carbon is crucial for high performance Li-S batteries. To this end, unlike conventional approaches to control the pore of carbon hosts, we demonstrate controlling the interfacial energy of the solution in the process of penetrating the sulfur-dissolved solution. We unveil, experimentally and theoretically, that the interfacial energy with the carbon surface of the sulfur solution is the key to driving complete encapsulation of sulfur. In the infiltration of sulfur solutions with N-methyl-2-pyrrolidone, we achieve complete encapsulation of sulfur, even up to 85 wt %. The sulfur fully encapsulated cathode achieves markedly high volumetric capacity and stable cycle operation in its Li-S battery applications. We achieve a volumetric capacity of 855 mAh/cm3 at 0.2C and a capacity reduction of 0.071% per cycle up to 300 cycles at 1C.

Piezoelectric Materials and Sensors for Structural Health Monitoring: Fundamental Aspects, Current Status, and Future Perspectives.

Structural health monitoring technology can assess the status and integrity of structures in real time by advanced sensors, evaluate the remaining life of structure, and make the maintenance decisions on the structures. Piezoelectric materials, which can yield electrical output in response to mechanical strain/stress, are at the heart of structural health monitoring. Here, we present an overview of the recent progress in piezoelectric materials and sensors for structural health monitoring. The article commences with a brief introduction of the fundamental physical science of piezoelectric effect. Emphases are placed on the piezoelectric materials engineered by various strategies and the applications of piezoelectric sensors for structural health monitoring. Finally, challenges along with opportunities for future research and development of high-performance piezoelectric materials and sensors for structural health monitoring are highlighted.

Risk factors of delirium in a paediatric intensive care unit: A prospective case series study.

BACKGROUND: Delirium is one of the most common complications in critically ill children. Once delirium occurs, it will cause physical and psychological distress in children and increase the length of their ICU stay and hospitalization costs. Understanding the risk factors for delirium in critically ill children can help develop targeted nursing interventions to reduce the incidence of delirium. AIMS: To investigate the incidence and the risk factors of delirium in the paediatric intensive care unit (PICU). STUDY DESIGN: We performed a prospective observational study in critically ill patients in the PICU between February and July 2020. Delirium was diagnosed by the Cornell Assessment of Paediatric Delirium (CAPD) and the Richmond Agitation Sedation Scale and analysed via univariate analysis and multivariate logistic regression to determine the independent risk factors of delirium in critically ill children. RESULTS: The study enrolled 315 patients ranging in age from 1-202 (65.3-54.3) months, with 56.2% (n = 177) being male. The incidence of delirium was 29.2% (n = 92) according to CAPD criteria. Among them, 33 cases (35.9%) were of hyperactive delirium, 16 cases (17.4%) were of hypoactive delirium, and 43 cases (46.7%) were of mixed delirium. By using stepwise logistic regression, the independent risk factors of delirium included mechanical ventilation (odds ratio [OR], 11.470; 95% confidence interval [CI], 4.283-30.721), nervous system disease (OR, 5.596; 95%CI, 2.445 to 12.809), developmental delay (OR, 5.157; 95% CI, 1.990-13.363), benzodiazepine (OR, 3.359; 95% CI 1.278-8.832), number of catheters (OR, 1.918; 95% CI, 1.425 to 2.582), and age (OR, 0.985; 95% confidence interval CI, 0.976-0.993). CONCLUSIONS: Delirium is a common complication in the PICU. The independent risk factors include mechanical ventilation, nervous system disease, developmental delay, benzodiazepines, higher number of catheters, and younger age. This study may help develop intervention strategies to reduce the incidence of delirium in critically ill children by targeting modifiable risk factors. RELEVANCE TO CLINICAL PRACTICE: Recommendations for practice include paying attention to high-risk children in the ICU who are prone to delirium, removing influencing factors as soon as possible, and providing targeted nursing interventions.

[Chemical constituents from whole herb of Hedyotis scandens].

This study aimed to investigate the chemical constituents in the water extract of the whole herb of Hedyotis scandens by silica gel, ODS, and MCI column chromatographies together with preparative high-performance liquid chromatography(HPLC). The structures of isolated constituents were identified by NMR, HR-ESI-MS, etc. Thirteen compounds were isolated and identified as methyl 4-benzoyloxy-3-methoxybenzeneacetate(1), 4-benzoyloxy-3-methoxybenzeneacetic acid(2), 3-(4-hydroxy-3-methoxyphenyl)-propanoic acid(3), salicylic acid(4), 3-hydroxy-4-methoxypyridine(5), syringic acid(6), hydroxycinnamic acid(7),(R)-6-methyl-4,6-bis(4-methylpent-3-enyl)cyclohexa-1,3-dienecarbaldehyde(8), 1,2-bis(4-hydroxy-3-methoxyphenyl)-1,3-propanediol(9), 1H-indole-3-carboxaldehyde(10), isoscopoletin(11), syringaresinol(12), and pinoresinol(13). Among them, compounds 1 and 2 were new phenolic acid compounds, compounds 3-5, 8-11, and 13 were isolated from this genus for the first time, and compounds 6, 7, and 12 were obtained from H. scandens for the first time. The activity test showed that compounds 1 and 10 had a certain inhibitory effect on Mycobacterium smegmatis, with MIC_(50) values of 58.5 and 33.3 µg·mL~(-1), respectively.

Usage of compromised lung volume in monitoring steroid therapy on severe COVID-19.

BACKGROUND: Quantitative computed tomography (QCT) analysis may serve as a tool for assessing the severity of coronavirus disease 2019 (COVID-19) and for monitoring its progress. The present study aimed to assess the association between steroid therapy and quantitative CT parameters in a longitudinal cohort with COVID-19. METHODS: Between February 7 and February 17, 2020, 72 patients with severe COVID-19 were retrospectively enrolled. All 300 chest CT scans from these patients were collected and classified into five stages according to the interval between hospital admission and follow-up CT scans: Stage 1 (at admission); Stage 2 (3-7 days); Stage 3 (8-14 days); Stage 4 (15-21 days); and Stage 5 (22-31 days). QCT was performed using a threshold-based quantitative analysis to segment the lung according to different Hounsfield unit (HU) intervals. The primary outcomes were changes in percentage of compromised lung volume (%CL, - 500 to 100 HU) at different stages. Multivariate Generalized Estimating Equations were performed after adjusting for potential confounders. RESULTS: Of 72 patients, 31 patients (43.1%) received steroid therapy. Steroid therapy was associated with a decrease in %CL (- 3.27% [95% CI, - 5.86 to - 0.68, P = 0.01]) after adjusting for duration and baseline %CL. Associations between steroid therapy and changes in %CL varied between different stages or baseline %CL (all interactions, P < 0.01). Steroid therapy was associated with decrease in %CL after stage 3 (all P < 0.05), but not at stage 2. Similarly, steroid therapy was associated with a more significant decrease in %CL in the high CL group (P < 0.05), but not in the low CL group. CONCLUSIONS: Steroid administration was independently associated with a decrease in %CL, with interaction by duration or disease severity in a longitudinal cohort. The quantitative CT parameters, particularly compromised lung volume, may provide a useful tool to monitor COVID-19 progression during the treatment process. Trial registration Clinicaltrials.gov, NCT04953247. Registered July 7, 2021, https://clinicaltrials.gov/ct2/show/NCT04953247.