Currently, the drug delivery system (DDS) based on nanomaterials has become a hot interdisciplinary research topic. One of the core issues is drug loading and controlled release, in which the key lever is carriers. Vaterite, as an inorganic porous nano-material, is one metastable structure of calcium carbonate, full of micro or nano porous. Recently, vaterite has attracted more and more attention, due to its significant advantages, such as rich resources, easy preparations, low cost, simple loading procedures, good biocompatibility and many other good points. Vaterite, gained from suitable preparation strategies, can not only possess the good drug carrying performance, like high loading capacity and stable loading efficiency, but also improve the drug release ability, showing the better drug delivery effects, such as targeting release, pH sensitive release, photothermal controlled release, magnetic assistant release, optothermal controlled release. At the same time, the vaterite carriers, with good safety itself, can protect proteins, enzymes, or other drugs from degradation or inactivation, help imaging or visualization with loading fluorescent drugs in vitro and in vivo, and play synergistic effects with other therapy approaches, like photodynamic therapy, sonodynamic therapy, and thermochemotherapy. Latterly, some renewed reports in drug loading and controlled release have led to their widespread applications in diverse fields, from cell level to clinical studies. This review introduces the basic characteristics of vaterite and briefly summarizes its research history, followed by synthesis strategies. We subsequently highlight recent developments in drug loading and controlled release, with an emphasis on the advantages, quantity capacity, and comparations. Furthermore, new opportunities for using vaterite in cell level and animal level are detailed. Finally, the possible problems and development trends are discussed.

Objective To investigate an automated pretreatment technology for detecting levels of free silica in workplace dust. Methods An fully automated pretreatment workstation for detecting free silica levels in workplace dust was developed by integrating graphite-controlled digestion temperature, online-controlled dilution of digestion solutions, and filtration endpoint recognition based on monitoring technology, combined with multi-channel synchronous measurements. Results The fully automatic pretreatment workstation was used to digest and filter 14 standard samples of free silica produced by three institutions, and then detected by pyrophosphate method. The result range of high-, medium-, and low-level free silica standard samples detection was 66.5%-84.8%, 40.0%-44.5%, and 2.1%-24.8%, respectively. The mean relative standard deviations were 3.9%, 1.4% and 1.5%. Conclusion The fully automated pretreatment workstation produced results that met relevant requirements. It can effectively replace the manual digestion and filtration steps of the pyrophosphate method to measure free silica levels in workplace dust and enable rapid detection of free silica in dust samples.

Objective To explore the predictive value of fat attenuation index(FAI)and fibrous plaque index(FPI)for the prognosis of patients with acute coronary syndrome(ACS).Methods A retrospective cohort study was conducted on 334 ACS patients undergoing percutaneous coronary intervention(PCI)in the First Affiliated Hospital of Army Military Medical University and Yongchuan Hospital of Chongqing Medical University from March 2021 to July 2023.All patients received coronary computed tomography angiography(CCTA)to measure FAI and FPI.According to the occurrence of major adverse cardiovascular events(MACE)with 1 year of follow-up,they were divided into MACE group(n=108)and non-MACE group(n=226).The baseline data,CCTA data and results of laboratory tests were collected and compared between the 2 groups.Multivariate logistic regression analysis was used to analyze the relationship of FAI and FPI with the prognosis of ACS patients,and ROC curve was drawn to evaluate its predictive efficiency.Results Among the 334 ACS patients,108(32.34%)experienced MACE.When compared with the non-MACE group,the MACE group exhibited significantly larger proportions of diabetes(72.22%vs 31.86%)and left main coronary artery disease(18.52%vs 7.08%),but lower success rate of operation(79.63%vs 93.81%,P<0.05).Radiologic results showed that the proportion of severe stenosis(20.37%vs 10.62%),FAI(-80.12±6.41 HU vs-72.34±7.09 HU)and FPI(0.58±0.41 vs 0.26±0.12)were obviously increased in the MACE group than the non-MACE group(P<0.05).Laboratory tests indicated that there were statistical differences between the 2 groups in high-density lipoprotein-cholesterol(HDL-C,1.20±0.15 vs 1.09±0.16 mmol/L),miR-126(0.91±0.12 vs 0.96±0.15)and SST2(38.45±5.67 vs 34.30±4.89 ng/mL,P<0.05).Multivariate Logistic regression analysis revealed that FAI(OR=1.200,95%CI:1.136～1.268),FPI(OR=63.157,95%CI:14.126～282.374),moderate stenosis(OR=1.332,95%CI:1.024～1.859),severe stenosis(OR=1.480,95%CI:1.074～2.039),miR-126(OR=0.007,95%CI:0.001～0.077),and sST2(OR=1.192,95%CI:1.113～1.277)were independent predictors of MACE(P<0.05).ROC curve analysis displayed that stenosis degree(AUC=0.622,95%CI:0.561～0.683,P=0.001),FAI(AUC=0.790,95%CI:0.741～0.839,P=0.001)and FPI(AUC=0.700,95%CI:0.638～0.761,P=0.001),miR-126(AUC=0.646,95%CI:0.584～0.707,P=0.001),sST2(AUC=0.700,95%CI:0.638～0.761,P=0.001)had certain predictive values for ACS prognosis.Conclusion Coronary FAI and FPI can be used as independent prognostic indicators of ACS patients,and their numerical changes are closely related to plaque stability and inflammatory state.

In this work,a fluorescent probe PIN was synthesized using indole-3-carbohydrazide and pyrenecarboxaldehyde as raw materials.PIN showed weak fluorescence emission in aqueous solution with acetonitrile volume fraction of 70％.However,when Cu2+was added to this aqueous solution of PIN,a new fluorescence emission peak appeared at 495 nm,and the intensity of this peak gradually increased with the increase of concentration of Cu2+,and also caused a significant change in the fluorescence color of the solution.In contrast,the addition of 15 kinds of other common metal ions did not cause such change.The detection limit of PIN for Cu2+was 78.7 nmol/L,which was much lower than the maximum permitting level of Cu2+in drinking water in hygienic standard for drinking water in China.Therefore,PIN was a highly selective and sensitive fluorescence-enhanced probe for Cu2+.Meanwhile,the addition of Cu2+could also cause a new absorption peak at 440 nm in the ultraviolet-visible absorption spectrum of the aqueous solution of PIN,and meanwhile the colorless PIN solution changed into yellow,exhibiting the performance of PIN as a colorimetric probe for Cu2+.By fitting with the Levenberg-Marquardt algorithm equation,the binding ratio of PIN to Cu2+was 2:1,and the binding constant was 3.42×1012 L2/mol2.In addition,the binding mode of PIN with Cu2+was explored by using proton nuclear magnetic resonance(1H NMR)titration experiments and density functional theory simulations.The results showed that the addition of Cu2+could cause the aggregation of PIN molecules to form excimers,thus showing highly selective recognition.Finally,PIN was made into a simple test strip,which could achieve rapid and convenient fluorescence detection of Cu2+in actual water samples.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

AIM:To investigate the role and mechanisms of p21 activated kinase 1(Pak1)in myocardial met-abolic reprogramming(MR)in diabetes mellitus(DM)mice and its protective effects on cardiomyocytes.METHODS:Pak1flox/flox(Pak1f/f)mice and cardiomyocyte-specific Pak1 knockout(Pak1CKO)mice were randomly divided into 4 groups(n=6 per group):Pak1f/f group,Pak1f/f+DM group,Pak1CKO group,and Pak1CKO+DM group.Diabetes was induced by in-traperitoneal injection of streptozotocin.Cardiac function was evaluated by echocardiography 6 weeks after successful mod-eling.Ventricular myocardium was harvested after euthanasia.Myocardial pathological changes and lipid accumulation were assessed by HE staining and oil red O staining.Protein expression levels of Pak1,p-Pak1,peroxisome proliferator-activated receptor α(PPARα),PPARγ,lipoprotein lipase(LPL),carnitine palmitoyltransferase 1(CPT1),scavenger receptor B2(SCARB2/CD36),fatty acid binding protein 3(FABP3),pyruvate dehydrogenase kinase 4(PDK4)and the ratio of phosphorylated pyruvate dehydrogenase E1α subunit(p-PDHA1)to PDHA1 were determined by Western blot.The mRNA expression levels of diacylglycerol acyltransferase 1/2(DGAT1/2)were detected by RT-qPCR.RESULTS:Compared with Pak1f/f group,both Pak1f/f+DM and Pak1CKO groups showed significantly decreased left ventricular ejection fraction(EF)and fractional shortening(FS),as well as increased left ventricular end-diastolic volume(LV Vold)and end-systolic volume(LV Vols)(P<0.01).Significant myocardial pathological damage with excessive lipid accumulation was observed.Myocardial p-Pak1 and Pak1 protein expression decreased(P<0.01),while PPARα,PPARγ,CPT1,LPL,CD36,FABP3,and PDK4 protein expression significantly increased(P<0.01),along with elevated p-PDHA1/PDHA1 ratio(P<0.01).mRNA expression levels of DGAT1 and DGAT2 were significantly reduced(P<0.01).The Pak1CKO+DM group showed the same trend as the Pak1f/f+DM group but with greater severity;compared with the Pak1f/f+DM group,the Pak1CKO+DM group still showed significant differences in all indicators except EF,FS,and LVVold(P<0.05 or P<0.01).CONCLUSION:Myocardial Pak1 protein expression is suppressed in diabetic mice,which mediates MR through activation of the PPARα/γ signaling pathway,resulting in increased myocardial fatty acid uptake and utiliza-tion while reducing glucose oxidation capacity.This leads to lipid accumulation in cardiomyocytes,myocardial damage,and cardiac systolic and diastolic dysfunction.

Objective:This study aimed to investigate the regulatory role and mechanism of myosin heavy chain 9 (MYH9) in the invasion of Zika virus (ZIKV) into human glioma cells (U251).Methods:Utilizing CRISPR/Cas9 technology, MYH9-knockout U251 cells (U251-MYH9 KD) were constructed. Following ZIKV infection, the protein expression levels, RNA load, and viral titer of ZIKV were detected through western blot (WB), Real-time fluorescence quantitative polymerase chain reaction (qPCR), and plaque formation assays, respectively. The infection efficiency of ZIKV in U251 cells treated with the MYH9 inhibitor blebbistatin was assessed. The binding and internalization efficiency of ZIKV were measured in U251-MYH9 KD cells. The interaction between MYH9 and the ZIKV envelope protein (E) was studied using co-immunoprecipitation (Co-IP). The effects of soluble MYH9 recombinant protein and anti-human MYH9 antibodies on ZIKV infection were evaluated by qPCR and plaque formation assays. Results:It was found that knockout or inhibition of MYH9 significantly suppressed ZIKV infection in U251 cells. MYH9 knockout notably inhibited the binding and internalization of ZIKV in U251 cells. MYH9 interacted with the ZIKV E protein, and both MYH9 recombinant protein and anti-human MYH9 antibodies, by blocking the binding of ZIKV E protein to cell surface MYH9, inhibited ZIKV infection in U251 cells in a dose-dependent manner.Conclusions:MYH9 facilitates ZIKV invasion into U251 cells through interaction with the ZIKV E protein.

[Objective]To explore the incremental cost of central line-associated bloodstream infections(CLABSI)after central venous catheterization(CVC)in critically ill patients in the intensive care unit(ICU),as well as the main cost of nosocomial infection prevention and control.By comparing these two costs,the medical personnel to pay more attention should CLABSI prevention and control from the perspectives of medical quality and economic benefits,and promote the implementation of prevention and control measures.[Methods]Cluster sampling was used to select 126 critically ill patients who underwent CVC in the ICU of a tertiary traditional Chinese medicine hospital from January 2021 to December 2023,including 65 cases in the CLABSI group and 61 in the non-CLABSI group.Patients'data were retrospectively collected from the hospital medical records,including the disease type,gender,age,length of hospital stay,outcome,and hospitalization expenses.The costs of different hand hygiene methods and differing approaches to environmental cleaning and disinfection were analyzed and compared.[Results]There were significant differences in the length of hospital stay(Z=-5.35,P<0.05)and total hospitalization expenses(Z=-6.79,P<0.05)between the CLABSI and non-CLABSI group.Total hospitalization expenses showed significant differences among patients with different lengths of hospital stay(H=43.01,P<0.05),with much higher median one in those with 60 or more days of hospital stay than other patients.Greater differences of median total hospitalization expenses were found in males than in females(Z=-3.98,P<0.05),as well as in patients aged 60-80 years than in patients of other ages(Z=-5.79,P<0.05).[Conclusions]The occurrence of CLABSI significantly increases the ICU patients'length of hospital stay and hospitalization expenses.There are differences in the costs of different hand hygiene methods and differing approaches to environmental cleaning and disinfection,but these costs are acceptable compared to the incremental costs directly attributable to CLABSI.Therefore,medical institutions should attach importance to the investment in prevention and control of nosocomial infections such as hand hygiene and environmental cleaning and disinfection,formulate practical,reasonable and feasible plans,and ensure their implementation,in order to avoid nosocomial infections,improve the medical quality,effectively control patients'length of hospital stay and hospitalization costs,and strive to maintain patient safety.

The therapeutic effects of Yueju Pills on depression and cardiovascular diseases have been widely recognized. Previous studies have shown that the drug can significantly improve depressive-like behaviors induced by chronic unpredictable mild stress(CUMS) combined with atherosclerosis(AS). Given the complex pathogenesis of psychocardiac diseases, this study integrated metabolomics and network pharmacology to systematically elucidate the mechanism of Yueju Pills in alleviating depressive symptoms in psychocardiac diseases. The results demonstrate that, after Yueju Pill intervention, the levels of 9 abnormal metabolites in the hippocampus restore to normal ranges, primarily involving key pathways or signaling pathways, including the cyclic adenosine monophosphate(cAMP), mammalian target of rapamycin(mTOR), glycine/serine/threonine metabolism, and aminoacyl-tRNA biosynthesis. In a high-fat diet-induced CUMS ApoE~(-/-) mouse model, Yueju Pills significantly increases adenosine monophosphate(AMP) levels and decreases L-alanine and D-glyceric acid levels in the hippocampus. In conclusion, Yueju Pills exert antidepressant effects by regulating multiple metabolic axes, including glycine/serine/threonine metabolism and the cAMP, mTOR signaling pathways. Network pharmacology predictions reveal that the treatment of CUMS combined with AS by its core active components may be realized through modulating pathways concerning neuroinflammation and synaptic plasticity, including serine/threonine-protein kinase 1(AKT1), mitogen-activated protein kinase 1(MAPK1), and prostaglandin-endoperoxide synthase 2(PTGS2). This study provides a theoretical reference for the clinical application of Yueju Pills in alleviating the depressive symptoms of psychocardiac diseases.
Animals ; Network Pharmacology ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Metabolomics ; Male ; Depression/genetics* ; Humans ; Hippocampus/drug effects* ; Mice, Inbred C57BL ; Signal Transduction/drug effects*

Investigating the correlation between micronucleus formation and male infertility has the potential to improve clinical diagnosis and deepen our understanding of pathological progression. Our study enrolled 2252 male patients whose semen was analyzed from March 2023 to July 2023. Their clinical data, including semen parameters and age, were also collected. Genetic analysis was used to determine whether the sex chromosome involved in male infertility was abnormal (including the increase, deletion, and translocation of the X and Y chromosomes), and subsequent semen analysis was conducted for clinical grouping purposes. The participants were categorized into five groups: normozoospermia, asthenozoospermia, oligozoospermia, oligoasthenozoospermia, and azoospermia. Patients were randomly selected for further study; 41 patients with normozoospermia were included in the control group and 117 patients with non-normozoospermia were included in the study group according to the proportions of all enrolled patients. Cytokinesis-block micronucleus (CBMN) screening was conducted through peripheral blood. Statistical analysis was used to determine the differences in micronuclei (MNi) among the groups and the relationships between MNi and clinical data. There was a significant increase in MNi in infertile men, including those with azoospermia, compared with normozoospermic patients, but there was no significant difference between the genetic and nongenetic groups in azoospermic men. The presence of MNi was associated with sperm concentration, progressive sperm motility, immotile spermatozoa, malformed spermatozoa, total sperm count, and total sperm motility. This study underscores the potential utility of MNi as a diagnostic tool and highlights the need for further research to elucidate the underlying mechanisms of male infertility.
Humans ; Male ; Infertility, Male/genetics* ; Adult ; Micronucleus Tests ; Semen Analysis ; Oligospermia/genetics* ; Azoospermia/genetics* ; Chromosome Aberrations ; Sperm Count ; Micronuclei, Chromosome-Defective ; Middle Aged