Converging evidences showed that people with diabetes mellitus (DM) have significantly higher risk for different cancers, of which the exact mechanism underlying the association has not been fully ...realized. Short-chain fatty acids (SCFAs), the fermentation products of the intestinal microbiota, are an essential source for energy supply in gut epithelial cells. They have been reported to improve intestinal barrier integrity, prevent microbial translocation, and further dampen inflammation. Gut dysbiosis and reduction in SCFA-producing bacteria as well as SCFAs production in the intestine are commonly seen in metabolic disorders including DM and obesity. Moreover, inflammation can contribute to tumor initiation and progression through multiple pathways, such as enhancing DNA damage, accumulating mutations in tumor suppressor genes Tp53, and activating nuclear factor-kappa B (NF-κB) signaling pathways. Based on these facts, we hypothesize that lower levels of microbial SCFAs resulted from gut dysbiosis in diabetic individuals, enhance microbial translocation, and increase the inflammatory responses, inducing tumorigenesis ulteriorly. To this end, we will discuss protective properties of microbial SCFAs and explore the pivotal roles SCFAs played in the link of DM with cancer, so as to take early precautions to reduce the risk of cancer in patients with DM.
There is a global move toward being “carbon neutral”. Reducing the use of coal to generate power has become an inevitable choice for many countries when transforming their energy structures. Many ...countries have proposed phasing out coal. China is a major energy producing and consuming country and intends to reach a carbon peak by 2030 and become carbon neutral by 2060. China has repeatedly emphasized coal reduction, but has not explicitly proposed phasing out coal, due to the influence of local governments, coal-related enterprises, and the public. This paper explores whether China could declare a “coal phase-out”, and the possible reasons for doing so, by constructing an evolutionary game model with two correlations. MATLAB was used to simulate the model results to determine the effectiveness of the fractal results of the model, and the entropy method was used to calculate the development level of “coal phase-out” related indicators in China and Germany. The results show that: (1) The government can phase out coal only when coal-related enterprises and the public can benefit from reducing coal production and consumption. In addition, these benefits are needed to ensure stable economic and social development without affecting people’s daily lives; (2) The development level of relevant indicators of “coal retreat” in China is lower than that in Germany. Based on these results, it is concluded that it is difficult for China to announce a “coal phase-out” at present. Faced with this reality, China should improve the efficiency of coal use, install carbon capture and storage facilities, vigorously develop renewable energy and reduce the share of coal in the energy system.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•The voriconazole trough concentration (VTC) was higher in elderly patients.•The proportion of patients with a VTC of >5 μg/mL was higher in elderly patients.•The procalcitonin concentration was ...associated with the VTC in elderly patients.•Procalcitonin concentrations of ≥1.31 ng/mL increased the incidence of a VTC of >5 μg/mL.•Voriconazole dose adjustment according to the procalcitonin concentration is necessary.
Data on therapeutic drug monitoring of voriconazole in elderly patients are limited. Impaired liver function and an inflammatory state in elderly individuals are hypothesized to impact the voriconazole serum level.
A total of 166 adult patients (317 trough concentrations) who underwent voriconazole therapeutic drug monitoring were enrolled. The voriconazole trough concentration, its associated covariates, and its correlation with adverse effects in 73 elderly (≥60 years) patients (116 trough concentrations) were analyzed and compared to those in 93 adult (<60 years) patients.
The voriconazole trough concentration was 4.31 ± 3.03 μg/mL (range, 0.4–15.5 μg/mL) in the elderly patients, which was significantly higher than the 3.11 ± 2.13 μg/mL (range, 0.4–14.3 μg/mL) in the adult patients (P = 0.001). The proportion of voriconazole trough concentrations higher than 5 μg/mL was 35.3% in the elderly patients, which was also significantly higher than the 15.4% in the adult patients (P < 0.001). A stepwise multivariable linear regression model showed that procalcitonin and gamma-glutamyl transpeptidase were independently associated factors in the elderly patients (OR = 2.590, 95% confidence interval CI = 1.506–3.673, P = 0.001; OR = −0.016, 95% CI = −0.027 to −0.006, P = 0.005). Receiver operating characteristic (ROC) curve analysis indicated that procalcitonin concentrations of ≥1.31 ng/mL increased the incidence of a voriconazole trough concentration higher than 5 μg/mL (95% CI = 0.53–0.87 μg/mL) (P = 0.03). The incidence of decreased albumin concentrations was higher in the elderly cohort than that in the adult cohort independent of the voriconazole trough concentration (P < 0.05).
The voriconazole trough concentrations in the elderly patients were significantly higher than those in the adult patients who received voriconazole therapy and were significantly affected by severe inflammation as evaluated by the procalcitonin concentration. Frequent monitoring of the voriconazole serum concentration and procalcitonin concentration during and after severe inflammation is critical to maintain the voriconazole serum concentration within the therapeutic range.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The aim of this study was to investigate the changes over a ten-year period in the resistance and epidemiological characteristics of Pseudomonas aeruginosa strains isolated from the Department of ...Respiratory in Southwest Hospital.
Antimicrobial resistance was detected using the plate double dilution method. PCR amplification and sequencing were performed to evaluate the carbapenemase genes and the oprD gene. Bacterial genotypes were analyzed by multilocus sequence typing (MLST). Quantitative real-time PCR experiments were performed to assess the expression of efflux pump (mexA and mexX) and ampC gene.
We collected 233 P. aeruginosa isolates in 2006–2007 and 128 isolates in 2016–2017. The resistance rate of P. aeruginosa strains to the tested antibiotics was significantly lower in 2016–2017 than in 2006–2007. The MLST results showed 27 genotypes in 2006–2007 and 18 genotypes in 2016–2017. ST235 was the most prevalent sequence type, and there was no significant change in the genotypes over the ten-year period. Both VIM-2 and IMP-4 genes were found in 2006–2007, whereas only IMP-4 was found in 2016–2017. The oprD mutational inactivation was the main factor responsible for carbapenem resistance, and the overexpression of mexX had a good correlation with aminoglycoside resistance.
These results indicated that the antibiotic resistance of P. aeruginosa in our respiratory department decreased. The loss of oprD gene was the main mechanism of carbapenem resistance, and mexX overexpression was the major contributing factor to aminoglycoside resistance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Migraine, a neurological disorder with a significant female predilection, is the leading cause of disability-adjusted life years (DALYs) in women of childbearing age (WCBA). There is ...currently a lack of comprehensive literature analysis on the overall global burden and changing trends of migraines in WCBA.
Methods
This study extracted three main indicators, including prevalence, incidence, and DALYs, related to migraine in WCBA from the Global Burden of Disease(GBD) database from 1990 to 2021. Our study presented point estimates with 95% uncertainty intervals (UIs). It evaluated the changing trends in the burden of migraine in WCBA using the estimated annual percentage change (EAPC) and percentage change.
Results
In 2021, the global prevalence, incidence, and DALYs cases of migraine among WCBA were 493.94 million, 33.33 million, and 18.25 million, respectively, with percentage changes of 48%, 43%, and 47% compared to 1990. Over the past 32 years, global prevalence rates and DALYs rates globally have increased, with an EAPC of 0.03 (95% UI: 0.02 to 0.05) and 0.04 (95% UI: 0.03 to 0.05), while incidence rates have decreased with an EAPC of -0.07 (95% UI: -0.08 to -0.05). Among the 5 Socio-Demographic Index (SDI) regions, in 2021, the middle SDI region recorded the highest cases of prevalence, incidence, and DALYs of migraine among WCBA, estimated at 157.1 million, 10.56 million, and 5.81 million, respectively, approximately one-third of the global total. In terms of age, in 2021, the global incidence cases for the age group 15–19 years were 5942.5 thousand, with an incidence rate per 100,000 population of 1957.02, the highest among all age groups. The total number of migraine cases and incidence rate among WCBA show an increasing trend with age, particularly in the 45–49 age group.
Conclusions
Overall, the burden of migraine among WCBA has significantly increased globally over the past 32 years, particularly within the middle SDI and the 45–49 age group. Research findings emphasize the importance of customized interventions aimed at addressing the issue of migraines in WCBA, thus contributing to the attainment of Sustainable Development Goal 3 set by the World Health Organization.
Immunocompromised individuals and those with lung dysfunction readily acquire pulmonary bacterial infections, which may cause serious diseases and carry a heavy economic burden. Maintaining adequate ...antibiotic concentrations in the infected tissues is necessary to eradicate resident bacteria. To specifically deliver therapeutics to the infected pulmonary tissues and enable controlled release of payloads at the infection site, a ROS-responsive material, i.e. 4-(hydroxymethyl) phenylboronic acid pinacol ester-modified α-cyclodextrin (Oxi-αCD), was employed to encapsulate moxifloxacin (MXF), generating ROS-responsive MXF-containing nanoparticles (MXF/Oxi-αCD NPs).
MXF/Oxi-αCD NPs were coated with DSPE-PEG and DSPE-PEG-folic acid, facilitating penetration of the sputum secreted by the infected lung and enabling the active targeting of macrophages in the inflammatory tissues. In vitro drug release experiments indicated that MXF release from Oxi-αCD NPs was accelerated in the presence of 0.5 mM H
O
. In vitro assay with Pseudomonas aeruginosa demonstrated that MXF/Oxi-αCD NPs exhibited higher antibacterial activity than MXF. In vitro cellular study also indicated that folic acid-modified MXF/Oxi-αCD NPs could be effectively internalized by bacteria-infected macrophages, thereby significantly eradicating resident bacteria in macrophages compared to non-targeted MXF/Oxi-αCD NPs. In a mouse model of pulmonary P. aeruginosa infection, folic acid-modified MXF/Oxi-αCD NPs showed better antibacterial efficacy than MXF and non-targeted MXF/Oxi-αCD NPs. Meanwhile, the survival time of mice was prolonged by treatment with targeting MXF/Oxi-αCD NPs.
Our work provides a strategy to overcome the mucus barrier, control drug release, and improve the targeting capability of NPs for the treatment of pulmonary bacterial infections.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Introduction
Colistin is regarded as one of the last-resort antibiotics against severe infections caused by carbapenem-resistant Enterobacteriaceae. Strains with cooccurrence of
mcr-9
and ...carbapenemase genes are of particular concern. This study aimed to investigate the genetic characteristics of a
bla
KPC-2
-carrying plasmid,
bla
NDM-1
-carrying plasmid and
mcr-9-
carrying plasmid coexisting in a carbapenem-resistant
Enterobacter hormaechei
isolate.
Methods
E. hormaechei
strain E1532 was subjected to whole-genome sequencing, and the complete nucleotide sequences of three resistance plasmids identified in the strain were compared with related plasmid sequences. The resistance phenotypes mediated by these plasmids were analyzed by plasmid transfer, carbapenemase activity and antimicrobial susceptibility testing.
Results
Whole-genome sequencing revealed that strain E1532 carries three different resistance plasmids, pE1532-KPC, pE1532-NDM and pE1532-MCR. pE1532-KPC harboring
bla
KPC-2
and pE1532-NDM harboring
bla
NDM-1
are highly identical to the IncR plasmid pHN84KPC and IncX3 plasmid pNDM-HN380, respectively. The
mcr-9-
carrying plasmid pE1532-MCR possesses a backbone highly similar to that of the IncHI2 plasmids R478 and p505108-MDR, though their accessory modules differ. These three coexisting plasmids carry a large number of resistance genes and contribute to high resistance to almost all antibiotics tested, except for amikacin, trimethoprim/sulfamethoxazole, tigecycline and polymyxin B. Most of the plasmid-mediated resistance genes are located in or flanked by various mobile genetic elements, facilitating horizontal transfer of antibiotic resistance genes.
Discussion
This is the first report of a single
E. hormaechei
isolate with coexistence of three resistance plasmids carrying
mcr-9
and the two most common carbapenemase genes,
bla
KPC-2
and
bla
NDM-1
. The prevalence and genetic features of these coexisting plasmids should be monitored to facilitate the establishment of effective strategies to control their further spread.
The impact of COVID-19 has been devastating on a global scale. The negative conversion time (NCT) of SARS-CoV-2 RNA is closely related to clinical manifestation and disease progression in COVID-19 ...patients. Our study aimed to predict factors associated with prolonged NCT of SARS-CoV-2 RNA in mild/moderate COVID-19 patients.
The clinical features, laboratory data and treatment outcomes of COVID-19 patients were retrospectively analyzed. Then univariate and multivariate analysis were used to screen out risk factors of influencing prolonged NCT of SARS-CoV-2 RNA.
Thirty-two hospitalized mild/moderate COVID-19 patients were enrolled. The general clinical symptoms were cough (78.1%), fever (75%), diarrhea (68.8%), expectoration (56.3%), and nausea (37.5%). More than 40% of the patients had decreased erythrocyte, hemoglobin and leucocyte and 93.8% patients were detected in abnormalities of chest CT. The median NCT of SARS-CoV-2 RNA was 19.5 days (IQR: 14.25-25). Univariate analysis found fever, nausea, diarrhea and abnormalities in chest CTs were positively associated with prolonged NCT of viral RNA (P< 0.05). The multivariate Cox proportional hazard model revealed that fever Exp (B), 0.284; 95% CI, 0.114-0.707; P<0.05 and nausea Exp (B), 0.257; 95%CI, 0.096-0.689; P<0.05 were two significant independent factors.
Fever and nausea were two significant independent factors in prolonged NCT of viral RNA in mild/moderate COVID-19 patients, which provided a useful references for disease progression and treatment of COVID-19.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Vibrio parahaemolyticus, a Gram-negative, halophilic bacterium, is a leading cause of acute gastroenteritis in humans. AphA and OpaR are the master quorum sensing (QS) regulators operating at low ...cell density (LCD) and high cell density (HCD), respectively. QsvR is an AraC-type protein that integrates into the QS system to control gene expression by directly controlling the transcription of
and
. However, the regulation of QsvR itself remains unclear to date. In this study, we show that
and
are transcribed as an operon,
-
. AphA indirectly activates the transcription of
at LCD, whereas OpaR and QsvR directly repress
transcription at HCD, leading to the highest expression levels of
occurs at LCD. Moreover, VPA0607 acts as an active RNase II-type protein in
and feedback inhibits the expression of QsvR at the post-transcriptional level. Taken together, this work deepens our understanding of the regulation of QsvR and enriches the integration mechanisms of QsvR with the QS system in
.
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