Research Competence in Clinical Nursing Insights From Chinese Nurses: A Cross-Sectional Survey.

AIM: To assess the research capacity of 3014 clinical nurses in northeastern China, examining their participation in research and self-assessed competencies to advance nursing practice. BACKGROUND: Nursing research is essential for the development of the nursing discipline, yet significant progress in enhancing the research capabilities of nursing staff has been limited over the past decades. Clinical nurses, central to the execution of research activities, need improved research skills to identify relevant topics and synthesise clinical experiences with the literature. DESIGN: A cross-sectional survey. METHODS: In 2023, using a convenience sampling method, a cross-sectional questionnaire survey was conducted on 3014 nurses in a Grade A tertiary hospital. The questionnaire included questions on basic information and scientific research, as well as a self-evaluation scale assessing the nurses' capability for conducting scientific research. RESULTS: Among the nurses participating in the survey, 29.66% (894) had published academic papers in Chinese, 2.06% (62) had published papers in Science Citation Index journals, 2.39% (72) had hosted nursing research projects, 5.87% (177) had participated in nursing research projects and 71% (2140) expressed their willingness to participate in nursing research activities. The average score on the self-evaluation of research capability was 54.08 ± 24.55, with scores ranging from 0 to 120. CONCLUSION: The clinical nurses' research capacity scores are at the midpoint of the scale (0-120), indicating basic research capabilities with room for improvement. There is a high willingness to engage in research. Nursing managers should consider these factors in training programmes and promote research activities to improve the team's scientific capability. RELEVANCE TO CLINICAL PRACTICE: This study reveals a critical gap between nurses' willingness and actual involvement in research, emphasising the need for enhanced research skills to improve nursing practice. PATIENT OR PUBLIC CONTRIBUTION: This study did not require patient or public involvement in its design, outcome measures or execution. The contribution of patients/members of the public was limited solely to data collection.

Therapeutic potential of coumestan Pks13 inhibitors for tuberculosis.

Polyketide synthase 13 (Pks13) is an important enzyme found in Mycobacterium tuberculosis (M. tuberculosis) that condenses two fatty acyl chains to produce α-alkyl ß-ketoesters, which in turn serve as the precursors for the synthesis of mycolic acids that are essential building blocks for maintaining the cell wall integrity of M. tuberculosis Coumestan derivatives have recently been identified in our group as a new chemotype that exert their antitubercular effects via targeting of Pks13. These compounds were active on both drug-susceptible and drug-resistant strains of M. tuberculosis as well as showing low cytotoxicity to healthy cells and a promising selectivity profile. No cross-resistance was found between the coumestan derivatives and first-line TB drugs. Here we report that treatment of M. tuberculosis bacilli with 15 times the MIC of compound 1, an optimized lead coumestan compound, resulted in a colony forming unit (CFU) reduction from 6.0 log10 units to below the limit of detection (1.0 log10 units) per mL culture, demonstrating a bactericidal mechanism of action. Single dose (10 mg/kg) pharmacokinetic studies revealed favorable parameters with a relative bioavailability of 19.4%. In a mouse infection and chemotherapy model, treatment with 1 showed dose-dependent mono-therapeutic activity, whereas treatment with 1 in combination with rifampin showed clear synergistic effects. Together these data suggest that coumestan derivatives are promising agents for further TB drug development.

A tandem CCCH type zinc finger protein gene CpC3H3 from Chimonanthus praecox promotes flowering and enhances drought tolerance in Arabidopsis.

BACKGROUND: CCCH-type zinc finger proteins play important roles in plant development and biotic/abiotic stress responses. Wintersweet (Chimonanthus praecox) is a popular ornamental plant with strong resistance to various stresses, which is a good material for exploring gene resource for stress response. In this study, we isolated a CCCH type zinc finger protein gene CpC3H3 (MZ964860) from flower of wintersweet and performed functional analysis with a purpose of identifying gene resource for floral transition and stress tolerance. RESULTS: CpC3H3 was predicted a CCCH type zinc finger protein gene encoding a protein containing 446 amino acids with five conserved C-X8-C-X5-C-X3-H motifs. CpC3H3 was localized in the cell membrane but with a nuclear export signal at the N-terminal. Transcripts of CpC3H3 were significantly accumulated in flower buds at floral meristem formation stage, and were induced by polyethylene glycol. Overexpression of CpC3H3 promoted flowering, and enhanced drought tolerance in transgenic A. thaliana. CpC3H3 overexpression affects the expression level of genes involved in flower inducement and stress responses. Further comparative studies on physiological indices showed the contents of proline and soluble sugar, activity of peroxidase and the rates of electrolyte leakage were significantly increased and the content of malondialdehyde and osmotic potential was significantly reduced in transgenic A. thaliana under PEG stress. CONCLUSION: Overall, CpC3H3 plays a role in flowering inducement and drought tolerance in transgenic A. thaliana. The CpC3H3 gene has the potential to be used to promote flowering and enhance drought tolerance in plants.

Association between night shift and sleep quality and health among Chinese nurses: A cross-sectional study.

AIM: To explore the sleep quality among Chinese nurses and identify the association between night shift and sleep quality and health. BACKGROUND: Chinese nurses have many night shifts; the effect of it regarding nurses' sleep quality and health is still not being explored. METHODS: This was a cross-sectional study. There were 3,206 nurse participants. The participants self-completed a sociodemographic questionnaire, the Pittsburgh Sleep Quality Index (PSQI) and the Cornell Medical Index (CMI). RESULTS: Night shift nurses demonstrated relatively worse sleep quality (55.1%) and more health problems (20.7%). Night shift work was significantly associated with poor sleep quality (ß = 0.96, confidence interval [CI] = 0.67-1.26) and poor health (ß = 2.01, CI = 0.15-3.88). Except for sleep medication (ß = 0.02, CI = -0.01, 0.05) and psychological health (ß = 0.38, CI = -0.27, 1.03), night shift work was significantly associated with other PSQI domains and physical health. CONCLUSION: Night shift work was a risk factor for nurses' sleep quality and health. Night shift nurses have more sleep disorders and physical health problems. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers should pay attention to the impact of shift work on nurses' sleep quality and health and reform the rotating shift work system to improve nurses' occupational health.

Revisiting the ß-Lactams for Tuberculosis Therapy with a Compound-Compound Synthetic Lethality Approach.

The suboptimal effectiveness of ß-lactam antibiotics against Mycobacterium tuberculosis has hindered the utility of this compound class for tuberculosis treatment. However, the results of treatment with a second-line regimen containing meropenem plus a ß-lactamase inhibitor were found to be encouraging in a case study of extensively drug-resistant tuberculosis (M. C. Payen, S. De Wit, C. Martin, R. Sergysels, et al., Int J Tuberc Lung Dis 16:558-560, 2012, https://doi.org/10.5588/ijtld.11.0414). We hypothesized that the innate resistance of M. tuberculosis to ß-lactams is mediated in part by noncanonical accessory proteins that are not considered the classic targets of ß-lactams and that small-molecule inhibitors of those accessory targets might sensitize M. tuberculosis to ß-lactams. In this study, we screened an NIH small-molecule library for the ability to sensitize M. tuberculosis to meropenem. We identified six hit compounds, belonging to either the N-arylindole or benzothiophene chemotype. Verification studies confirmed the synthetic lethality phenotype for three of the N-arylindoles and one benzothiophene derivative. The latter was demonstrated to be partially bioavailable via oral administration in mice. Structure-activity relationship studies of both structural classes identified analogs with potent antitubercular activity, alone or in combination with meropenem. Transcriptional profiling revealed that oxidoreductases, MmpL family proteins, and a 27-kDa benzoquinone methyltransferase could be the targets of the N-arylindole potentiator. In conclusion, our compound-compound synthetic lethality screening revealed novel small molecules that were capable of potentiating the action of meropenem, presumably via inhibition of the innate resistance conferred by ß-lactam accessory proteins. ß-Lactam compound-compound synthetic lethality may be an alternative approach for drug-resistant tuberculosis.

ytiB and ythA Genes Reduce the Uranium Removal Capacity of Bacillus atrophaeus.

Two Bacillus atrophaeus strains, the first being a highly stress-resistant ATCC 9372 strain and the Ua strain identified from a chromium mine by our lab, differ in their abilities to tolerate and remove Uranium (VI) from contaminated water. An increase in U(VI) concentration in growth media led to a decrease in the tolerance and bio-remedial capacity of both strains. However, under high concentrations of U(VI) in the growth media, the ATCC 9372 strain demonstrated a higher tolerance and a higher removal capacity than the Ua strain. Two approaches, transcriptome sequencing and transgenic technology, were used to elucidate the relationship between particular genes within these two strains and their U(VI) removal capacity. Sequencing confirmed the expression of two genes unique to the Ua strain, previously designated ytiB and ythA. They encode putative proteins that show the highest levels of identity to carbonic anhydrase and cytochrome bd terminal oxidase I, respectively. Using the pBE-S DNA vector, ytiB and ythA were transformed into the ATCC 9372 strain of Bacillus atrophaeus. Under a U(VI) concentration of 120 mg/L, the removal rates of the transgenic ATCC 9372-ytiB and ATCC 9372-ythA strains decreased by 7.55% and 7.43%, respectively, compared to the removal rate of the control strain transformed with empty plasmid. The results suggest that both ythA and ytiB genes have a negative influence on the uranium removing capacity of Bacillus atrophaeus. This finding will help to elucidate the molecular mechanisms of uranium removal by bacteria.

Ultrahigh-Power-Factor Carbon Nanotubes and an Ingenious Strategy for Thermoelectric Performance Evaluation.

An ingenious strategy is put forward to evaluate accurately the thermoelectric performance of carbon nanotube (CNT) thin films, including thermal conductivity, electrical conductivity, and Seebeck coefficient in the same direction. The results reveal that the as-prepared CNT interconnected films and CNT fibers possess enormous potential of thermoelectric applications because of their ultrahigh power factors.

Engineering a hierarchically micro-/nanostructured Si@Au-based artificial enzyme with improved accessibility of active sites for enhanced catalysis.

The active site accessibility and high loading of gold nanoparticles (AuNPs) are key factors affecting the catalytic activity of supported AuNP-based catalysts. However, the preparation of supported AuNP-based catalysts with highly accessible active sites still remains a challenge. Herein, sphere-on-sphere (SoS) silica microspheres with a hierarchical structure, good dispersion and high surface density of thiol groups (10 SH nm-2) are prepared and used as a platform for the growth of high-density AuNPs. The obtained hierarchical Si@Au micro-/nanostructure consisting of 0.55 µm SoS silica microspheres and 7.3 nm AuNPs (SoS-0.55@Au-7.3) is found to show excellent peroxidase-mimicking activity (Km = 0.033 mM and Vmax = 34.6 × 10-8 M s-1) with merits of high stability and good reusability. Furthermore, the as-obtained SoS-0.55@Au-7.3-based system can sensitively detect hydrogen peroxide (H2O2) with a low detection limit of 1.6 µM and a wide linear range from 2.5 µM to 1.0 mM. The high catalytic activity, excellent stability and good reusability of SoS-0.55@Au-7.3 imply its great prospects in biosensing and biomedical analysis.

Development and evaluation of a PICC virtual simulator in neonatal nursing: A randomized controlled trial.

BACKGROUND: Peripherally Inserted Central Catheter (PICC) is essential in neonatal care, especially for critically ill infants. Traditional training for neonatal PICC insertion faces challenges such as high costs and limited practice opportunities. Virtual simulation technology has emerged as a potential training tool, providing a realistic, risk-free learning environment. OBJECTIVES: The study aimed to assess the effectiveness of a virtual simulation teaching system in neonatal PICC care training, focusing on improving nursing students' knowledge， skills and interest in pediatric nursing. DESIGN: A quasi-experimental design was used, with assessments conducted before and after the activity. PARTICIPANTS: The study involved 58 graduate nursing students from China Medical University, divided into experimental and control groups. METHODS: The System Usability Scale (SUS) was utilized to assess teachers' experiences with the PICC virtual simulation software. Students' perceptions of the software and their interest in pediatric nursing were measured using Self-Administered Questionnaires. Furthermore, Theoretical and Operational Assessments were applied to determine the extent of students' knowledge and practical skills before and after experimentation. RESULTS: Teachers and students have favorably evaluated the software system, with notable improvements in theoretical scores following testing. While the virtual simulation system does not enhance practical skills, it does increase student interest in pediatric nursing and employment. CONCLUSIONS: This neonatal virtual simulation software serves as a complement to, rather than a replacement for, traditional clinical training. Its integration into educational programs significantly enhances learning outcomes.

Improvement of glucolipid metabolism and oxidative stress via modulating PI3K/Akt pathway in insulin resistance HepG2 cells by chickpea flavonoids.

Chickpea (Cicer arietinum L.) is a significant dietary source of flavonoids and the hypoglycemic activity were investigated in this study. Firstly, total twenty nine chickpea flavonoids were identified by UPLC-MS/MS with ononin, cyanidin-3-O-glucoside, astragalin, cynaroside, kaempferol-3-O-rutinoside, biochanin A, and daidzin being the most abundant among them. Our results demonstrated that chickpea flavonoids regulated glucose metabolism and lipid metabolism, and reduced oxidative stress in insulin resistance HepG2 cells. Furthermore, insulin resistance was ameliorated by chickpea flavonoids through the activation of insulin receptor substrate1 (IRS1), phosphoinositide 3-kinase (PI3K), and phosphorylated protein kinase B (Akt) in HepG2 cells. More importantly, key differential metabolites include L-tryptophan, L-tyrosine, l-glutamine and linoleic acid were reserved by chickpea flavonoids and correlated with glucolipid metabolism and oxidative stress in IR-HepG2 cells. In conclusion, these results indicated that chickpea flavonoids might act as potential natural products regulating insulin resistance in HepG2 cells.

Impact of molecular weight and gastrointestinal digestion on the immunomodulatory effects of Lycium barbarum polysaccharides.

In traditional Chinese medicine, Lycium barbarum is of rich medicinal value, and its polysaccharides are particularly interesting due to their significant pharmacological effects and potential health benefits. This study investigated the immunomodulatory effects of Lycium barbarum polysaccharides (LBPs) by examining their interaction with the TLR4/MD-2 complex and the impacts of gastrointestinal digestion on these interactions. We discovered that the affinity binding of LBPs for TLR4/MD-2 and their cytokine induction capability are influenced by molecular weight, with medium-sized LBPs (100-300 kDa) exhibiting stronger binding affinity and induction capability. Conversely, LBPs smaller than 10 kDa showed reduced activity. Additionally, the content of arabinose and galactose within the LBPs fractions was found to correlate positively with both receptor affinity and cytokine secretion. Simulated gastrointestinal digestion resulted in the degradation of LBPs into smaller fragments that are rich in glucose. Although these fragments exhibited decreased binding affinity to the TLR4/MD-2 complex, they maintained their activity to promote cytokine production. Our findings highlight the significance of molecular weight and specific monosaccharide composition in the immunomodulatory function of LBPs and emphasize the influence of gastrointestinal digestion on the effects of LBPs. This research contributes to a better understanding of the mechanisms underlying the immunomodulatory effects of traditional Chinese medicine polysaccharides and their practical application.

In situ comparison of osteogenic effects of polymer-based scaffolds with different degradability by integrated scaffold model.

Polymer-based scaffolds with different degradability have been investigated to screen the matrix whose degradation rate is more closely matched with the bone regeneration rate. However, these comparisons are inclined to be compromised by the animal individual differences. In this study, we constructed an integrated scaffold model comprising four parts with different degradability and bioactivity to achieve an in situ comparison of bone regeneration ability of different scaffolds. Slow-degradable polycaprolactone (PCL), fast-degradable poly (lactic-co-glycolic acid) (PLGA), and silica-coated PCL and PLGA scaffolds were assembled into a round sheet to form a hydroxyapatite (HA)-free integrated scaffold. HA-doped PCL, PLGA, and silica-coated PCL and PLGA scaffolds were assembled to create an HA-incorporated integrated scaffold. The in vivo experimental results demonstrated that the local acid microenvironment caused by the rapid degradation of PLGA interfered with the osteogenic process promoted by PCL-based scaffolds in defect areas implanted with HA-free integrated scaffolds. Since the incorporation of HA alleviated the acidic microenvironment to some extent, each scaffold in HA-incorporated scaffolds exhibited its expected bone regeneration capacity. Consequently, it is feasible to construct an integrated structure for comparing the osteogenic effects of various scaffolds in situ, when there is no mutual interference between the materials. The strategy presented in this study inspired the structure design of biomaterials to enable in situ comparison of bone regeneration capacity of scaffolds.

Nano-laponite encapsulated coaxial fiber scaffold promotes endochondral osteogenesis.

Osteoinductive supplements without side effects stand out from the growth factors and drugs widely used in bone tissue engineering. Lithium magnesium sodium silicate hydrate (laponite) nanoflake is a promising bioactive component for bone regeneration, attributed to its inherent biosafety and effective osteoinductivity. Up to now, the in vivo osteogenic potential and mechanisms of laponite-encapsulated fibrous membranes remain largely unexplored. This study presents a unique method for homogeneously integrating high concentrations of laponite RDS into a polycaprolactone (PCL) matrix by dispersing laponite RDS sol into the polymer solution. Subsequently, a core-shell fibrous membrane (10RP-PG), embedding laponite-loaded PCL in its core, was crafted using coaxial electrospinning. The PCL core's slow degradation and the shell's gradient degradation enabled the sustained release of bioactive ions (Si and Mg) from laponite. In vivo studies on a critical-sized calvarial bone defect model demonstrated that the 10RP-PG membrane markedly enhanced bone formation and remodeling by accelerating the process of endochondral ossification. Further transcriptome analysis suggested that osteogenesis in the 10RP-PG membrane is driven by Mg and Si from endocytosed laponite, activating pathways related to ossification and endochondral ossification, including Hippo, Wnt and Notch. The fabricated nanocomposite fibrous membranes hold great promise in the fields of critical-sized bone defect repair.

A sequential macrophage activation strategy for bone regeneration: A micro/nano strontium-releasing composite scaffold loaded with lipopolysaccharide.

Effective tissue repair relies on the orchestration of different macrophage phenotypes, both the M2 phenotype (promotes tissue repair) and M1 phenotype (pro-inflammatory) deserve attention. In this study, we propose a sequential immune activation strategy to mediate bone regeneration, by loading lipopolysaccharide (LPS) onto the surface of a strontium (Sr) ions -contained composite scaffold, which was fabricated by combining Sr-doped micro/nano-hydroxyapatite (HA) and dual degradable matrices of polycaprolactone (PCL) and poly (lactic-co-glycolic acid) (PLGA). Our strategy involves the sequential release of LPS to promote macrophage homing and induce the expression of the pro-inflammatory M1 phenotype, followed by the release of Sr ions to suppress inflammation. In vitro and in vivo experiments demonstrated that, the appropriate pro-inflammatory effects at the initial stage of implantation, along with the anti-inflammatory effects at the later stage, as well as the structural stability of the scaffolds conferred by the composition, can synergistically promote the regeneration and repair of bone defects.

Preliminary construction of a microecological evaluation model for uranium-contaminated soil.

With the extensive development of nuclear energy, soil uranium contamination has become an increasingly prominent problem. The development of evaluation systems for various uranium contamination levels and soil microhabitats is critical. In this study, the effects of uranium contamination on the carbon source metabolic capacity and microbial community structure of soil microbial communities were investigated using Biolog microplate technology and high-throughput sequencing, and the responses of soil biochemical properties to uranium were also analyzed. Then, ten key biological indicators as reliable input variables, including arylsulfatase, biomass nitrogen, metabolic entropy, microbial entropy, Simpson, Shannon, McIntosh, Nocardioides, Lysobacter, and Mycoleptodisus, were screened by random forest (RF), Boruta, and grey relational analysis (GRA). The optimal uranium-contaminated soil microbiological evaluation model was obtained by comparing the performance of three evaluation methods: partial least squares regression (PLS), support vector regression (SVR), and improved particle algorithm (IPSO-SVR). Consequently, partial least squares regression (PLS) has a higher R2 (0.932) and a lower RMSE value (0.214) compared to the other. This research provides a new evaluation method to describe the relationship between soil ecological effects and biological indicators under nuclear contamination.

NSP6 inhibits the production of ACE2-containing exosomes to promote SARS-CoV-2 infectivity.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global pandemic, which severely endangers public health. Our and others' works have shown that the angiotensin-converting enzyme 2 (ACE2)-containing exosomes (ACE2-exos) have superior antiviral efficacies, especially in response to emerging variants. However, the mechanisms of how the virus counteracts the host and regulates ACE2-exos remain unclear. Here, we identified that SARS-CoV-2 nonstructural protein 6 (NSP6) inhibits the production of ACE2-exos by affecting the protein level of ACE2 as well as tetraspanin-CD63 which is a key factor for exosome biogenesis. We further found that the protein stability of CD63 and ACE2 is maintained by the deubiquitination of proteasome 26S subunit, non-ATPase 12 (PSMD12). NSP6 interacts with PSMD12 and counteracts its function, consequently promoting the degradation of CD63 and ACE2. As a result, NSP6 diminishes the antiviral efficacy of ACE2-exos and facilitates the virus to infect healthy bystander cells. Overall, our study provides a valuable target for the discovery of promising drugs for the treatment of coronavirus disease 2019. IMPORTANCE: The outbreak of coronavirus disease 2019 (COVID-19) severely endangers global public health. The efficacy of vaccines and antibodies declined with the rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants. Angiotensin-converting enzyme 2-containing exosomes (ACE2-exos) therapy exhibits a broad neutralizing activity, which could be used against various viral mutations. Our study here revealed that SARS-CoV-2 nonstructural protein 6 inhibited the production of ACE2-exos, thereby promoting viral infection to the adjacent bystander cells. The identification of a new target for blocking SARS-CoV-2 depends on fully understanding the virus-host interaction networks. Our study sheds light on the mechanism by which the virus resists the host exosome defenses, which would facilitate the study and design of ACE2-exos-based therapeutics for COVID-19.

Disorganized adrenocortical zonational structure in COVID-19 patients: Implications of critical illness duration.

Aberrant adrenal function has been frequently reported in COVID-19 patients, but histopathological evidence remains limited. This retrospective autopsy study aims to scrutinize the impact of COVID-19 duration on adrenocortical zonational architecture and peripheral corticosteroid reactivity. The adrenal glands procured from 15 long intensive care unit (ICU)-stay COVID-19 patients, 9 short ICU-stay COVID-19 patients, and 20 matched controls. Subjects who had received glucocorticoid treatment prior to sampling were excluded. Applying hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining, we disclosed that the adrenocortical zonational structure was substantially disorganized in COVID-19 patients, which long ICU-stay patients manifested a higher prevalence of severe disorganization (67%) than short ICU-stay patients (11%; P = 0.0058). The adrenal cortex of COVID-19 patients exhibited a 40% decrease in the zona glomerulosa (ZG) area and a 74% increase in the zona fasciculata (ZF) area (both P < 0.0001) relative to controls. Furthermore, among long ICU-stay COVID-19 patients, the ZG area diminished by 31% (P = 0.0004), and the ZF area expanded by 27% (P = 0.0004) in comparison to short ICU-stay patients. The zona reticularis (ZR) area remained unaltered. Nuclear translocation of corticosteroid receptors in the liver and kidney of long ICU-stay COVID-19 patients was at least 43% lower than in short ICU-stay patients (both P < 0.05). These findings underscore the necessity for clinicians to monitor adrenal function in long-stay COVID-19 patients.

The histamine receptor H1 acts as an alternative receptor for SARS-CoV-2.

Numerous host factors, in addition to human angiotensin-converting enzyme 2 (hACE2), have been identified as coreceptors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrating broad viral tropism and diversified druggable potential. We and others have found that antihistamine drugs, particularly histamine receptor H1 (HRH1) antagonists, potently inhibit SARS-CoV-2 infection. In this study, we provided compelling evidence that HRH1 acts as an alternative receptor for SARS-CoV-2 by directly binding to the viral spike protein. HRH1 also synergistically enhanced hACE2-dependent viral entry by interacting with hACE2. Antihistamine drugs effectively prevent viral infection by competitively binding to HRH1, thereby disrupting the interaction between the spike protein and its receptor. Multiple inhibition assays revealed that antihistamine drugs broadly inhibited the infection of various SARS-CoV-2 mutants with an average IC50 of 2.4 µM. The prophylactic function of these drugs was further confirmed by authentic SARS-CoV-2 infection assays and humanized mouse challenge experiments, demonstrating the therapeutic potential of antihistamine drugs for combating coronavirus disease 19.IMPORTANCEIn addition to human angiotensin-converting enzyme 2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can utilize alternative cofactors to facilitate viral entry. In this study, we discovered that histamine receptor H1 (HRH1) not only functions as an independent receptor for SARS-CoV-2 but also synergistically enhances ACE2-dependent viral entry by directly interacting with ACE2. Further studies have demonstrated that HRH1 facilitates the entry of SARS-CoV-2 by directly binding to the N-terminal domain of the spike protein. Conversely, antihistamine drugs, primarily HRH1 antagonists, can competitively bind to HRH1 and thereby prevent viral entry. These findings revealed that the administration of repurposable antihistamine drugs could be a therapeutic intervention to combat coronavirus disease 19.

Increased adrenal steroidogenesis and suppressed corticosteroid responsiveness in critical COVID-19.

BACKGROUND: The effect of coronavirus disease 2019 (COVID-19) on adrenal endocrine metabolism in critically ill patients remains unclear. This study aimed to investigate the alterations in adrenal steroidogenic activity, elucidate underlying mechanisms, provide in situ histopathological evidence, and examine the clinical implications. METHODS: The comparative analyses of the adrenal cortices from 24 patients with fatal COVID-19 and 20 matched controls were performed, excluding patients previously treated with glucocorticoids. SARS-CoV-2 and its receptors were identified and pathological alterations were examined. Furthermore, histological examinations, immunohistochemical staining and ultrastructural analyses were performed to assess corticosteroid biosynthesis. The zona glomerulosa (ZG) and zona fasciculata (ZF) were then dissected for proteomic analyses. The biological processes that affected steroidogenesis were analyzed by integrating histological, proteomic, and clinical data. Finally, the immunoreactivity and responsive genes of mineralocorticoid and glucocorticoid receptors in essential tissues were quantitatively measured to evaluate corticosteroid responsiveness. FINDINGS: The demographic characteristics of COVID-19 patients were comparable with those of controls. SARS-CoV-2-like particles were identified in the adrenocortical cells of three patients; however, these particles did not affect cellular morphology or steroid synthesis compared with SARS-CoV-2-negative specimens. Although the adrenals exhibited focal necrosis, vacuolization, microthrombi, and inflammation, widespread degeneration was not evident. Notably, corticosteroid biosynthesis was significantly enhanced in both the ZG and ZF of COVID-19 patients. The increase in the inflammatory response and cellular differentiation in the adrenal cortices of patients with critical COVID-19 was positively correlated with heightened steroidogenic activity. Additionally, the appearance of more dual-ZG/ZF identity cells in COVID-19 adrenals was in accordance with the increased steroidogenic function. However, activated mineralocorticoid and glucocorticoid receptors and their responsive genes in vital tissues were markedly reduced in patients with critical COVID-19. INTERPRETATION: Critical COVID-19 was characterized by potentiated adrenal steroidogenesis, associated with increased inflammation, enhanced differentiation and elevated dual-ZG/ZF identity cells, alongside suppressed corticosteroid responsiveness. These alterations implied the reduced effectiveness of conventional corticosteroid therapy and underscored the need for evaluation of the adrenal axis and corticosteroid sensitivity.

Chemical composition of kabuli and desi chickpea (Cicer arietinum L.) cultivars grown in Xinjiang, China.

Chickpeas are a very important legume crop and have abundant protein, carbohydrate, lipid, fiber, isoflavone, and mineral contents. The chemical compositions of the four chickpea species (Muying-1, Keying-1, Desi-1, Desi-2) from Xinjiang, China, were analyzed, and 46 different flavonoids in Muying-1 were detected. The moisture content ranged from 7.64 ± 0.01 to 7.89 ± 0.02 g/100 g, the content of starch in the kabuli chickpeas was greater than that in the desi chickpeas, the total ash content ranged from 2.59 ± 0.05 to 2.69 ± 0.03 g/100 g and the vitamin B1 content of the chickpeas ranged from 0.31 to 0.36 mg/100 g. The lipid content ranged from 6.35 to 9.35 g/100 g and the major fatty acids of chickpeas were linoleic, oleic, and palmitic acids. Both kabuli and desi chickpeas have a high content of unsaturated fatty acids (USFAs), Muying-1 and Desi-1 contained the highest level of linoleic acid, and Keying-1 had the highest oleic acid content. The protein level ranged from 19.79 ± 2.89 to 23.38 ± 0.30 g/100 g, and the main amino acids were aspartic acid, glutamic acid, and arginine acid. The four chickpea species had significant amounts of essential amino acids (EAAs). Forty-six varieties of flavonoids in Muying-1 were determined by ultra high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-QqQ-MS) analysis, and there were higher levels of conjugate flavonoids (55.95%) than free flavonoids (44.05%). Isoflavones were the most abundant flavonoids in Muying-1, and among the isoflavones, daidzin had the highest content, followed by biochanin A and genistin. Muying-1 was rich in daidzin, biochanin A, genistin, troxerutin, isorhamnetin, astilbin, L-epicatechin, astragalin, acacetin, hyperoside, and myricitrin. Information provided in the study will be helpful to further understand the chemical composition of chickpeas and be beneficial to the development of chickpeas.