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1.
PLoS Negl Trop Dis ; 18(7): e0012024, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39012922

ABSTRACT

Central China has been reported to be one of the most important endemic areas of zoonotic infection by spotted fever group rickettsiae (SFGR), severe fever with thrombocytopenia syndrome virus (SFTSV) and hantaan virus (HTNV). Due to similar clinical symptoms, it is challenging to make a definite diagnosis rapidly and accurately in the absence of microbiological tests. In the present study, an all-in-one real-time PCR assay was developed for the simultaneous detection of nucleic acids from SFGR, SFTSV and HTNV. Three linear standard curves for determining SFGR-ompA, SFTSV-L and HTNV-L were obtained within the range of 101-106 copies/µL, with the PCR amplification efficiencies ranging from 93.46% to 96.88% and the regression coefficients R2 of >0.99. The detection limit was 1.108 copies/µL for SFGR-ompA, 1.075 copies/µL for SFTSV-L and 1.006 copies/µL for HTNV-L, respectively. Both the within-run and within-laboratory coefficients of variation on the cycle threshold (Ct) values were within the range of 0.53%-2.15%. It was also found there was no statistical difference in the Ct values between single template and multiple templates (PSFGR-ompA = 0.186, PSFTSV-L = 0.612, PHTNV-L = 0.298). The sensitivity, specificity, positive and negative predictive value were all 100% for determining SFGR-ompA and SFTSV-L, 97%, 100%, 100% and 99.6% for HTNV-L, respectively. Therefore, the all-in-one real-time PCR assay appears to be a reliable, sensitive, rapid, high-throughput and low cost-effective method to diagnose the zoonotic infection by SFGR, SFTSV and HTNV.

2.
Vet Microbiol ; 296: 110171, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38981202

ABSTRACT

Intestinal pathogenic Escherichia coli (InPEC) is one of the most common causes of bacterial diarrhea in farm animals, including profuse neonatal diarrhea and post weaning diarrhea (PWD) in piglets. In this study, we investigated the prevalence of InPEC and associated primary virulence factors among 543 non-duplicate E. coli isolates from diarrheal pigs from 15 swine farms in southern China. Six major virulence genes associated with InPEC were identified among 69 (12.71 %) E. coli isolates and included est (6.62 %), K88 (4.79 %), elt (3.68 %), eae (1.47 %), stx2 (0.92 %) and F18 (0.55 %). Three pathotypes of InPEC were identified including ETEC (8.10 %), EPEC (1.29 %) and STEC/ETEC (0.92 %). In particular, K88 was only found in ETEC from breeding farms, whereas F18 was only present in STEC/ETEC hybrid from finishing farms. Whole genome sequence analysis of 37 E. coli isolates revealed that InPEC strains frequently co-carried multiple antibiotic resistance gene (ARG). est, elt and F18 were also found to co-locate with ARGs on a single IncFIB/IncFII plasmid. InPEC isolates from different pathotypes also possessed different profiles of virulence genes and antimicrobial resistance genes. Population structure analysis demonstrated that InPEC isolates from different pathotypes were highly heterogeneous whereas those of the same pathotype were extremely similar. Plasmid analysis revealed that K88 and/or est/elt were found on pGX18-2-like/pGX203-2-like and pGX203-1-like IncFII plasmids, while F18 and elt/est, as well as diverse ARGs were found to co-locate on IncFII/IncFIB plasmids with a non-typical backbone. Moreover, these key virulence genes were flanked by or adjacent to IS elements. Our findings indicated that both clonal expansion and horizontal spread of epidemic IncFII plasmids contributed to the prevalence of InPEC and the specific virulence genes (F4, F18, elt and est) in the tested swine farms.

3.
World J Gastrointest Oncol ; 16(6): 2404-2418, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38994138

ABSTRACT

BACKGROUND: Research on gastrointestinal mucosal adenocarcinoma (GMA) is limited and controversial, and there is no reference tool for predicting postoperative survival. AIM: To investigate the prognosis of GMA and develop predictive model. METHODS: From the Surveillance, Epidemiology, and End Results database, we collected clinical information on patients with GMA. After random sampling, the patients were divided into the discovery (70% of the total, for model training), validation (20%, for model evaluation), and completely blind test cohorts (10%, for further model evaluation). The main assessment metric was the area under the receiver operating characteristic curve (AUC). All collected clinical features were used for Cox proportional hazard regression analysis to determine factors influencing GMA's prognosis. RESULTS: This model had an AUC of 0.7433 [95% confidence intervals (95%CI): 0.7424-0.7442] in the discovery cohort, 0.7244 (GMA: 0.7234-0.7254) in the validation cohort, and 0.7388 (95%CI: 0.7378-0.7398) in the test cohort. We packaged it into Windows software for doctors' use and uploaded it. Mucinous gastric adenocarcinoma had the worst prognosis, and these were protective factors of GMA: Regional nodes examined [hazard ratio (HR): 0.98, 95%CI: 0.97-0.98, P < 0.001)] and chemotherapy (HR: 0.62, 95%CI: 0.58-0.66, P < 0.001). CONCLUSION: The deep learning-based tool developed can accurately predict the overall survival of patients with GMA postoperatively. Combining surgery, chemotherapy, and adequate lymph node dissection during surgery can improve patient outcomes.

4.
Opt Lett ; 49(13): 3572-3575, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38950212

ABSTRACT

We demonstrate the post-induction of high-quality microcavities on a silicon photonic crystal (PC) waveguide by integrating a few-layer GaSe crystal, which promises efficient on-chip optical frequency conversions. The integration of GaSe shifts the dispersion bands of the PC waveguide mode into the bandgap, resulting in localized modes confined by the bare PC waveguides. Thanks to the small contrast of refractive index at the boundaries of the microcavity, it is reliable to obtain quality factors exceeding 104. With the enhanced light-GaSe interaction by the microcavity modes and GaSe's high second-order nonlinearity, remarkable second-harmonic generation (SHG) and sum-frequency generation (SFG) are achieved with continuous-wave (CW) lasers.

5.
Biosci Trends ; 18(3): 212-218, 2024.
Article in English | MEDLINE | ID: mdl-38987161

ABSTRACT

One important challenge for global development is aging. China is one of the world's countries with the highest elderly population and the most rapid aging; in 2022, the percentage of the population over 65 was 14.9%; by 2050, it is expected to rise to 26.1%. China's health security, elderly care, and healthcare services are facing serious challenges as a result of this aging trend. With 80% of provinces including medical and elderly care in national basic public health care programs, China has adopted a proactive national plan to combat population aging. Moreover, geriatric departments have been established at 69.3% of public general hospitals at secondary and higher tiers, 48% of provinces have devises preventive interventions for disability and dementia in the elderly, 48 percent of provinces are serving as test regions for medical care related to rehabilitation, and 49 cities are involved in long-term care insurance (LTCI) trials that encompass 170 million people. There are 4,259 medical and health care facilities that provide hospice care services, 152 hospice care pilot regions, and 87,000 pairs of contracts between medical and health care facilities and elderly care providers. These developments provide a strong basis, but there are still major obstacles to overcome. The Chinese Government is urged to adopt early preventive measures, offer more ongoing, practical, and cost-effective diagnostic and treatment services, allocate resources equitably, and use intelligent technologies to enhance elderly care. The ultimate goals are to lessen the financial burden, enhance the health of the elderly, and offer a vital global resource.


Subject(s)
Healthy Aging , China/epidemiology , Humans , Aged , Health Services for the Aged , Aging , Delivery of Health Care
6.
Sci Rep ; 14(1): 15737, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977804

ABSTRACT

The COVID-19 pandemic has significantly transformed the infection spectrum of various pathogens. This study aimed to evaluate the impact of the COVID-19 pandemic on Staphylococcus aureus (S. aureus) infections among pediatric patients with community acquired pneumonia (CAP). We retrospectively reviewed pediatric CAP admissions before (from 2018 to 2019) and during (from 2020 to 2022) the COVID-19 pandemic. The epidemiology and antimicrobial resistance (AMR) profiles of S. aureus isolates were examined to assess the pandemic's effect. As a result, a total of 399 pediatric CAP patients with S. aureus infections were included. The positivity rate, gender, and age distribution of patients were similar across both periods. There was a marked reduction in respiratory co-infections with Haemophilus influenzae (H. influenzae) during the COVID-19 pandemic, compared to 2019. Additionally, there were significant changes in the resistance profiles of S. aureus isolates to various antibiotics. Resistance to oxacillin and tetracycline increased, whereas resistance to penicillin, gentamicin, and quinolones decreased. Notably, resistance to erythromycin significantly decreased in methicillin-resistant S. aureus (MRSA) strains. The number of S. aureus isolates, the proportion of viral co-infections, and the number of resistant strains typically peaked seasonally, primarily in the first or fourth quarters of 2018, 2019, and 2021. However, shifts in these patterns were noted in the first quarter of 2020 and the fourth quarter of 2022. These findings reveal that the COVID-19 pandemic has significantly altered the infection dynamics of S. aureus among pediatric CAP patients, as evidenced by changes in respiratory co-infections, AMR patterns, and seasonal trends.


Subject(s)
Anti-Bacterial Agents , COVID-19 , Community-Acquired Infections , Staphylococcal Infections , Staphylococcus aureus , Humans , COVID-19/epidemiology , COVID-19/microbiology , COVID-19/complications , Community-Acquired Infections/epidemiology , Community-Acquired Infections/microbiology , Community-Acquired Infections/drug therapy , Female , Male , Child , Child, Preschool , Retrospective Studies , Staphylococcus aureus/drug effects , Staphylococcus aureus/isolation & purification , Infant , Staphylococcal Infections/epidemiology , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Adolescent , Coinfection/epidemiology , Coinfection/microbiology , SARS-CoV-2/isolation & purification , SARS-CoV-2/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Pandemics , Hospitalization , Drug Resistance, Bacterial
7.
Medicine (Baltimore) ; 103(27): e38759, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38968537

ABSTRACT

Vedolizumab (VDZ), a monoclonal antibody to α4ß7 integrin, is available for patients with moderate-to-severe ulcerative colitis (UC). This study planned to assess the real-world effectiveness and safety of VDZ for UC patients in Northern China. We enrolled patients with moderate-to-severe UC who underwent VDZ induction therapy from March 2021 to November 2022 at the Affiliated Hospital of Qingdao University. The primary outcome was clinical remission at weeks 14 and 52 after the initial VDZ therapy. Overall adverse events and risk factors associated with loss of response (LOR) were also evaluated. Seventy-three UC patients receiving VDZ therapy were included in this study. The rates of clinical response, clinical remission, and steroid-free clinical remission were 69.9%, 39.7%, and 34.2% at week 14 and 90.5%, 66.7%, and 64.4% at week 52, respectively. The mucosal remission rates were 37.5% (18/48) at week 14 ±â€…8 and 27.3% (9/33) at week 52 ±â€…16, while only 2 and 3 patients achieved mucosal healing at weeks 14 ±â€…8 and 52 ±â€…16, respectively. Of the UC patients, 23.3% experienced adverse events associated with VDZ, most of which were mild and self-limiting. Until the last follow-up, 37 of 73 UC patients experienced LOR during the maintenance period. Patients with a higher ulcerative colitis endoscopic severity index (UCEIS), partial Mayo scores (PMS), or hemoglobin below 120 g/L at baseline were more likely to experience LOR after VDZ induction therapy. VDZ is an effective and safe agent for patients with moderate-to-severe UC in Northern China. A high baseline UCEIS, PMS, or hemoglobin < 120 g/L may be an independent risk factor for LOR during the maintenance period.


Subject(s)
Antibodies, Monoclonal, Humanized , Colitis, Ulcerative , Gastrointestinal Agents , Severity of Illness Index , Humans , Colitis, Ulcerative/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Male , Female , Adult , China , Middle Aged , Gastrointestinal Agents/therapeutic use , Gastrointestinal Agents/adverse effects , Treatment Outcome , Remission Induction/methods , Young Adult
8.
AAPS J ; 26(4): 83, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39009955

ABSTRACT

Salts of weakly basic drugs can partially dissociate in formulations, to give basic drugs and counter acids. The aim of the present study was to clarify the effect of physicochemical properties on the basic drug-acid-polymer interactions and salt-polymer miscibility, and to explain the influence mechanism at the molecular level. Six maleate salts with different physicochemical properties were selected and PVA was used as the film forming material. The relationship between the physicochemical properties and the miscibility was presented with multiple linear regression analysis. The existence state of salts in formulations were determined by XRD and Raman imaging. The stability of salts was characterized by NMR and XPS. The intermolecular interactions were investigated by FTIR and NMR. The results showed that the salt-PVA miscibility was related to polar surface area of salts and Tg of free bases, which represented hydrogen bond interaction and solubility potential. The basic drug-acid-PVA intermolecular interactions determined the existence state and bonding pattern of the three molecules. Meanwhile, the decrease of the stability after formulation increased the number of free bases in orodispersible films, which in turn affected the miscibility with PVA. The study provided references for the rational design of PVA based orodispersible films.


Subject(s)
Polyvinyl Alcohol , Solubility , Polyvinyl Alcohol/chemistry , Administration, Oral , Drug Stability , Maleates/chemistry , Chemistry, Pharmaceutical/methods , Hydrogen Bonding , Spectroscopy, Fourier Transform Infrared , X-Ray Diffraction
9.
J Exp Bot ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39021198

ABSTRACT

Grain filling is a critical process for improving crop production under adverse conditions caused by climate change. Here, using a quantitative method, we quantified post-anthesis source-sink relationships of a large data set to assess the contribution of remobilized pre-anthesis assimilates to grain growth for both biomass and nitrogen. The data set came from 13 years' semi-controlled field experimentation, in which six bread wheat genotypes were grown at plot scale under contrasting temperature, water, and nitrogen regimes. On average, grain biomass was ~10% higher than post-anthesis aboveground biomass accumulation across regimes and genotypes. Overall, the estimated relative contribution (%) of remobilized assimilates to grain biomass became increasingly significant with increasing stress intensity, ranging from virtually nil to 100%. This percentage was altered more by water and nitrogen regimes than by temperature, indicating the greater impact of water or nitrogen regimes relative to high temperatures under our experimental conditions. Relationships between grain nitrogen demand and post-anthesis nitrogen uptake were generally insensitive to environmental conditions, as there was always significant remobilization of nitrogen from vegetative organs, which helped to stabilize the amount of grain nitrogen. Moreover, variations in the relative contribution of remobilized assimilates with environmental variables were genotype-dependent. Our analysis provides an overall picture of post-anthesis source-sink relationships and pre-anthesis assimilate contributions to grain filling across (non-)environmental factors, and highlights that designing wheat adaption to climate change should account for complex multi-factor interactions.

10.
Sci Rep ; 14(1): 12737, 2024 06 03.
Article in English | MEDLINE | ID: mdl-38830922

ABSTRACT

The COVID-19 pandemic has altered the infection landscape for many pathogens. This retrospective study aimed to compare Haemophilus influenzae (H. influenzae) infections in pediatric CAP patients hospitalized before (2018-2019) and during (2020-2022) the COVID-19 pandemic. We analyzed the clinical epidemiology and antimicrobial resistance (AMR) patterns of H. influenzae from a tertiary hospital in southwest China. A total of 986 pediatric CAP patients with H. influenzae-associated infections were included. Compared to 2018, the positivity rate increased in 2019 but dropped significantly in 2020. Although it rose in the following 2 years, the rate in 2022 remained significantly lower than in 2019. Patients' age during the pandemic was significantly higher than in 2018 and 2019, while gender composition remained similar across both periods. Notably, there were significant changes in co-infections with several respiratory pathogens during the pandemic. Resistance rates of H. influenzae isolates to antibiotics varied, with the highest resistance observed for ampicillin (85.9%) and the lowest for cefotaxime (0.0%). Resistance profiles to various antibiotics underwent dramatic changes during the COVID-19 pandemic. Resistance to amoxicillin-clavulanate, cefaclor, cefuroxime, trimethoprim-sulfamethoxazole, and the proportion of multi-drug resistant (MDR) isolates significantly decreased. Additionally, MDR isolates, alongside isolates resistant to specific drugs, were notably prevalent in ampicillin-resistant and ß-lactamase-positive isolates. The number of pediatric CAP patients, H. influenzae infections, and isolates resistant to certain antibiotics exhibited seasonal patterns, peaking in the winter of 2018 and 2019. During the COVID-19 pandemic, sharp decreases were observed in February 2020, and there was no resurgence in December 2022. These findings indicate that the COVID-19 pandemic has significantly altered the infection spectrum of H. influenzae in pediatric CAP patients, as evidenced by shifts in positivity rate, demographic characteristics, respiratory co-infections, AMR patterns, and seasonal trends.


Subject(s)
Anti-Bacterial Agents , COVID-19 , Community-Acquired Infections , Haemophilus Infections , Haemophilus influenzae , Humans , COVID-19/epidemiology , COVID-19/complications , Male , Female , Haemophilus influenzae/drug effects , Haemophilus influenzae/isolation & purification , Child , Child, Preschool , Haemophilus Infections/epidemiology , Haemophilus Infections/drug therapy , Haemophilus Infections/microbiology , Retrospective Studies , Community-Acquired Infections/epidemiology , Community-Acquired Infections/drug therapy , Community-Acquired Infections/microbiology , Infant , China/epidemiology , Anti-Bacterial Agents/therapeutic use , Hospitalization , Adolescent , Pandemics , Coinfection/epidemiology , Coinfection/drug therapy , Coinfection/microbiology , SARS-CoV-2/isolation & purification , SARS-CoV-2/drug effects , Drug Resistance, Bacterial
11.
Pediatr Hematol Oncol ; : 1-10, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38867542

ABSTRACT

Patients with newly diagnosed hematological malignancies often present with a considerable cellular burden, leading to complications including hyperkalemia. However, pseudohyperkalemia, arising from in vitro cell lysis, can pose challenges in clinical practice. Although pseudohyperkalemia is frequently reported in adult hematological malignancies, its occurrence in pediatric patients is underreported, and its incidence in this demographic remains unclear. We retrospectively reviewed the medical records of pediatric patients who received a new diagnosis of hematological malignancies from 2011 to 2022 at Taichung Veterans General Hospital. Hyperkalemia was defined by a serum or plasma potassium level exceeding 5.5 mEq/L. Pseudohyperkalemia was defined by 1) a potassium decrease of over 1 mEq/L in within 4 h without intervention or 2) the absence of electrocardiography changes indicative of hyperkalemia. Cases with apparent red blood cell hemolysis were excluded. A total of 157 pediatric patients with a new diagnosis of hematological malignancies were included, 14 of whom exhibited hyperkalemia. Among these 14 cases, 7 cases (4.5%) were of pseudohyperkalemia. This rate increased to 21.2% in patients with initial hyperleukocytosis. Pseudohyperkalemia was associated with a higher initial white blood cell count and lower serum sodium level. All episodes of pseudohyperkalemia occurred in the pediatric emergency department, where samples were obtained as plasma, whereas all true hyperkalemia cases were observed in the ordinary ward or intensive care unit, where samples were obtained as serum. Timely recognition of pseudohyperkalemia is crucial to avoiding unnecessary potassium-lowering interventions in pediatric patients with newly diagnosed hematological malignancies.

12.
J Pharm Pharmacol ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38934298

ABSTRACT

OBJECTIVES: The aim of this study was to investigate the therapeutic effects and related mechanisms of Tanshinone IIA and Tetramethylpyrazine O/W composite nanoemulsions on Alzheimer's disease (AD) rats. METHODS: The therapeutic effect of TSN/TMP O/W NEs on AD rats was evaluated by behavioral tests, H&E, Nissl, and Immunohistochemistry staining. ELISA and Western blot were used to analyze the mechanism. KEY FINDINGS: The results showed that TSN/TMP O/W NEs could down-regulate the expression of Bax and Caspase-3 proteins, decrease the level of MDA, increase the expression of SOD and GSH-Px, and alleviate cognitive impairment in AD rats. CONCLUSIONS: TSN/TMP O/W NEs can inhibit MAPK/ERK/CREB signaling pathway and effectively alleviate cognitive impairment, oxidative stress injury, and neuronal apoptosis in AD rats.

13.
Redox Biol ; 74: 103229, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38870781

ABSTRACT

BACKGROUND: Nuclear erythroid 2-related factor 2 (Nrf2), a transcription factor, is critically involved in the regulation of oxidative stress and inflammation. However, the role of endothelial Nrf2 in atherogenesis has yet to be defined. In addition, how endothelial Nrf2 is activated and whether Nrf2 can be targeted for the prevention and treatment of atherosclerosis is not explored. METHODS: RNA-sequencing and single-cell RNA sequencing analysis of mouse atherosclerotic aortas were used to identify the differentially expressed genes. In vivo endothelial cell (EC)-specific activation of Nrf2 was achieved by injecting adeno-associated viruses into ApoE-/- mice, while EC-specific knockdown of Nrf2 was generated in Cdh5CreCas9floxed-stopApoE-/- mice. RESULTS: Endothelial inflammation appeared as early as on day 3 after feeding of a high cholesterol diet (HCD) in ApoE-/- mice, as reflected by mRNA levels, immunostaining and global mRNA profiling, while the immunosignal of the end-product of lipid peroxidation (LPO), 4-hydroxynonenal (4-HNE), started to increase on day 10. TNF-α, 4-HNE, and erastin (LPO inducer), activated Nrf2 signaling in human ECs by increasing the mRNA and protein expression of Nrf2 target genes. Knockdown of endothelial Nrf2 resulted in augmented endothelial inflammation and LPO, and accelerated atherosclerosis in Cdh5CreCas9floxed-stopApoE-/- mice. By contrast, both EC-specific and pharmacological activation of Nrf2 inhibited endothelial inflammation, LPO, and atherogenesis. CONCLUSIONS: Upon HCD feeding in ApoE-/- mice, endothelial inflammation is an earliest event, followed by the appearance of LPO. EC-specific activation of Nrf2 inhibits atherosclerosis while EC-specific knockdown of Nrf2 results in the opposite effect. Pharmacological activators of endothelial Nrf2 may represent a novel therapeutic strategy for the treatment of atherosclerosis.


Subject(s)
Apolipoproteins E , Atherosclerosis , Endothelial Cells , Inflammation , Lipid Peroxidation , NF-E2-Related Factor 2 , Animals , Humans , Male , Mice , Apolipoproteins E/genetics , Apolipoproteins E/deficiency , Apolipoproteins E/metabolism , Atherosclerosis/metabolism , Atherosclerosis/genetics , Atherosclerosis/pathology , Disease Models, Animal , Endothelial Cells/metabolism , Inflammation/metabolism , Inflammation/genetics , Mice, Knockout , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/genetics , Oxidative Stress
14.
Infection ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38848016

ABSTRACT

PURPOSE: The COVID-19 pandemic has altered the infection dynamics of numerous pathogens. This study aimed to elucidate its impact on Streptococcus pneumoniae (S. pneumoniae) infections in children with community acquired pneumonia (CAP). METHODS: A retrospective analysis was conducted in pediatric CAP patients admitted before (2018-2019) and during (2020-2022) the COVID-19 pandemic. The epidemiology and antimicrobial resistance (AMR) patterns of S. pneumoniae were compared to reveal the impact of the pandemic. RESULTS: A total of 968 S. pneumoniae-associated pediatric CAP patients were enrolled. Although the positivity rate and gender of patients were stable across both periods, the age notably increased in 2021 and 2022. Additionally, significant changes were observed in the co-infections with several pathogens and the resistance rates to certain antibiotics during the COVID-19 pandemic. The resistance rate to clindamycin and quinupristin-dalfopristin increased, whereas the resistance rate to tetracycline, trimethoprim-sulfamethoxazole, telithromycin, and proportion of multi-drug resistant isolates decreased. The number of S. pneumoniae strains and resistant isolates exhibited similar seasonal patterns in 2018 and 2019, peaking in November or December with another minor peak in March or April. During the COVID-19 pandemic, there was a sharp decrease in February 2020 and no resurgence was observed at the end of 2022. Additionally, the minor peak was absent in 2020 and shifted to other months in 2021 and 2022. CONCLUSIONS: The COVID-19 pandemic has markedly altered the infection spectrum of S. pneumoniae in pediatric CAP patients, as evidenced by shifts in the age of patients, respiratory co-infections, AMR patterns, and seasonal trends.

15.
Int J Pharm ; 659: 124284, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38810934

ABSTRACT

The study aimed to create a low loading, high retention, easier to apply O/W mometasone furoate (MF) cream using a chemical enhancer (CE) approach to provide more options for patients with atopic dermatitis (AD) and to investigate molecular mechanisms of its increased release and retention. A Box-Behnken design determined the optimal formulation based on stability and in vitro skin retention. Evaluations included appearance, rheological properties, irritation, in vivo tissue distribution and pharmacodynamics. Molecular mechanisms of enhanced release were studied using high-speed centrifugation, molecular dynamics and rheology. The interaction between the CE, MF and skin was studied by tape stripping, CLSM, ATR-FTIR and SAXS. The formulation was optimized to contain 0.05% MF and used 10% polyglyceryl-3 oleate (POCC) as the CE. There was no significant difference from Elocon® cream in in vivo retention and pharmacodynamics but increased in vivo retention by 3.14-fold and in vitro release by 1.77-fold compared to the basic formulation. POCC reduced oil phase cohesive energy density, enhancing drug mobility and release. It disrupted skin lipid phases, aiding drug entry and formed hydrogen bonds, prolonging retention. This study highlights POCC as a CE in the cream, offering insights for semi-solid formulation development.


Subject(s)
Drug Liberation , Mometasone Furoate , Skin Cream , Skin , Mometasone Furoate/administration & dosage , Mometasone Furoate/pharmacokinetics , Mometasone Furoate/chemistry , Animals , Skin Cream/administration & dosage , Skin Cream/chemistry , Skin/metabolism , Skin/drug effects , Administration, Cutaneous , Male , Skin Absorption/drug effects , Chemistry, Pharmaceutical/methods , Glycerol/chemistry , Glycerol/analogs & derivatives , Dermatitis, Atopic/drug therapy , Female , Excipients/chemistry , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/pharmacokinetics , Drug Compounding/methods , Oleic Acid/chemistry , Polymers/chemistry
16.
Bioorg Chem ; 148: 107463, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38776649

ABSTRACT

Thrombosis leads to elevated mortality rates and substantial medical expenses worldwide. Human factor IXa (HFIXa) protease is pivotal in tissue factor (TF)-mediated thrombin generation, and represents a promising target for anticoagulant therapy. We herein isolated novel DNA aptamers that specifically bind to HFIXa through systematic evolution of ligands by exponential enrichment (SELEX) method. We identified two distinct aptamers, seq 5 and seq 11, which demonstrated high binding affinity to HFIXa (Kd = 74.07 ± 2.53 nM, and 4.93 ± 0.15 nM, respectively). Computer software was used for conformational simulation and kinetic analysis of DNA aptamers and HFIXa binding. These aptamers dose-dependently prolonged activated partial thromboplastin time (aPTT) in plasma. We further rationally optimized the aptamers by truncation and site-directed mutation, and generated the truncated forms (Seq 5-1t, Seq 11-1t) and truncated-mutated forms (Seq 5-2tm, Seq 11-2tm). They also showed good anticoagulant effects. The rationally and structurally designed antidotes (seq 5-2b and seq 11-2b) were competitively bound to the DNA aptamers and effectively reversed the anticoagulant effect. This strategy provides DNA aptamer drug-antidote pair with effective anticoagulation and rapid reversal, developing advanced therapies by safe, regulatable aptamer drug-antidote pair.


Subject(s)
Antidotes , Aptamers, Nucleotide , Factor IXa , Aptamers, Nucleotide/chemistry , Aptamers, Nucleotide/pharmacology , Humans , Factor IXa/antagonists & inhibitors , Factor IXa/metabolism , Antidotes/pharmacology , Antidotes/chemistry , Antidotes/chemical synthesis , Dose-Response Relationship, Drug , Anticoagulants/pharmacology , Anticoagulants/chemistry , Structure-Activity Relationship , Molecular Structure , SELEX Aptamer Technique
17.
Nanoscale ; 16(22): 10597-10606, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38758161

ABSTRACT

Tribocatalysis is a method that converts mechanical energy into chemical energy. In this study, we synthesized tungsten bronze structured Ba0.75Sr0.25Nb1.9Ta0.1O6 ferroelectric ceramic submicron powder using a traditional solid-state route, and the powder exhibited excellent performance in tribocatalytic water splitting for hydrogen production. Under the friction stirring of three polytetrafluoroethylene (PTFE) magnetic stirring bars in pure water, the rate of hydrogen generation by the Ba0.75Sr0.25Nb1.9Ta0.1O6 ferroelectric submicron powder is 200 µmol h-1 g-1, and after 72 hours, the accumulated hydrogen production reaches 15 892.8 µmol g-1. Additionally, this ferroelectric tungsten bronze ferroelectric material also exhibits excellent tribocatalytic degradation ability toward RhB dyes, with degradation efficiency reaching 96% in 2 hours. The study of tribocatalysis based on tungsten bronze ferroelectric materials represents a significant step forward in versatile energy utilization for clean energy and environmental wastewater degradation.

18.
mSystems ; 9(6): e0116423, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38747582

ABSTRACT

Salmonella 4,[5],12:i:-, a monophasic variant of Salmonella Typhimurium, has emerged as a global cause of multidrug-resistant salmonellosis and has become endemic in many developing and developed countries, especially in China. Here, we have sequenced 352 clinical isolates in Guangdong, China, during 2009-2019 and performed a large-scale collection of Salmonella 4,[5],12:i:- with whole genome sequencing (WGS) data across the globe, to better understand the population structure, antimicrobial resistance (AMR) genomic characterization, and transmission routes of Salmonella 4,[5],12:i:- across Guangdong. Salmonella 4,[5],12:i:- strains showed broad genetic diversity; Guangdong isolates were found to be widely distributed among the global lineages. Of note, we identified the formation of a novel Guangdong clade (Bayesian analysis of population structure lineage 1 [BAPS1]) genetically diversified from the global isolates and likely emerged around 1990s. BAPS1 exhibits unique genomic features, including large pan-genome, decreased ciprofloxacin susceptibility due to mutation in gyrA and carriage of plasmid-mediated quinolone resistance (PMQR) genes, and the multidrug-resistant IncHI2 plasmid. Furthermore, high genetic similarity was found between strains collected from Guangdong, Europe, and North America, indicating the association with multiple introductions from overseas. These results suggested that global dissemination and local clonal expansion simultaneously occurred in Guangdong, China, and horizontally acquired resistance to first-line and last-line antimicrobials at local level, underlying emergences of extensive drug and pan-drug resistance. Our findings have increased the knowledge of global and local epidemics of Salmonella 4,[5],12:i:- in Guangdong, China, and provided a comprehensive baseline data set essential for future molecular surveillance.IMPORTANCESalmonella 4,[5],12:i:- has been regarded as the predominant pandemic serotype causing diarrheal diseases globally, while multidrug resistance (MDR) constitutes great public health concerns. This study provided a detailed and comprehensive genome-scale analysis of this important Salmonella serovar in the past decade in Guangdong, China. Our results revealed the complexity of two distinct transmission modes, namely global transmission and local expansion, circulating in Guangdong over a decade. Using phylogeography models, the origin of Salmonella 4,[5],12:i:- was predicted from two aspects, year and country, that is, Salmonella 4,[5],12:i:- emerged in 1983, and was introduced from the UK, and subsequently differentiated into the local endemic lineage circa 1991. Additionally, based on the pan-genome analysis, it was found that the gene accumulation rate in local endemic BAPS 1 lineage was higher than in other lineages, and the horizontal transmission of MDR IncHI2 plasmid associated with high resistance played a major role, which showed the potential threat to public health.


Subject(s)
Drug Resistance, Multiple, Bacterial , Salmonella Infections , Whole Genome Sequencing , China/epidemiology , Drug Resistance, Multiple, Bacterial/genetics , Humans , Salmonella Infections/microbiology , Salmonella Infections/epidemiology , Salmonella Infections/transmission , Salmonella Infections/drug therapy , Anti-Bacterial Agents/pharmacology , Genome, Bacterial/genetics , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Microbial Sensitivity Tests , Phylogeny , Genomics , Plasmids/genetics
19.
Angew Chem Int Ed Engl ; : e202407518, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38752452

ABSTRACT

Gold nanoclusters exhibiting concomitant photothermy (PT) and photoluminescence (PL) under near-infrared (NIR) light irradiation are rarely reported, and some fundamental issues remain unresolved for such materials. Herein, we concurrently synthesized two novel rod-shaped Au nanoclusters, Au52(PET)32 and Au66(PET)38 (PET = 2-phenylethanethiolate), and precisely revealed that their kernels were 4 × 4 × 6 and 5 × 4 × 6 face-centered cubic (fcc) structures, respectively, based on the numbers of Au layers in the [100], [010], and [001] directions. Following the structural growth mode from Au52(PET)32 to Au66(PET)38, we predicted six more novel nanoclusters. The concurrent synthesis provides rational comparison of the two nanoclusters on the stability, absorption, emission and photothermy, and reveals the aspect ratio-related properties. An interesting finding is that the two nanoclusters exhibit concomitant PT and PL under 785 nm light irradiation, and the PT and PL are in balance, which was explained by the qualitative evaluation of the radiative and non-radiative rates. The ligand effects on PT and PL were also investigated.

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