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Abstract Background Abnormal blood potassium levels are associated with an increased risk of cardiometabolic diseases and mortality in the general population; however, evidence regarding the association between dyskalemia and mortality among patients with cardiovascular disease (CVD) remains inconclusive. This study aimed to evaluate the association of potassium levels with all-cause and cardiovascular mortality among patients with CVD. Methods PubMed, Embase, Web of Science, and Cochrane Library databases were searched up to August 2023 to identify relevant cohort studies among patients with CVD, such as myocardial infarction, stroke, and heart failure. Abnormal potassium levels were considered as hypokalemia or hyperkalemia. The primary outcomes were all-cause mortality based on follow-up length (including in-hospital, short-term and long-term mortality) and cardiovascular mortality. The methodological quality of included studies was assessed by using the Newcastle-Ottawa Scale. The pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models. Restricted cubic splines were applied to explore the dose-response relationship. Results Thirty-one cohort studies involving 227,645 participants with an average age of 68.3 years were included in the meta-analysis, all of which achieved moderate to high quality. Hyperkalemia was significantly associated with an approximately 3.0-fold increased risk of all-cause in-hospital mortality (RR:2.78,95CI%:1.92,4.03), 1.8-fold of all-cause short-term mortality (RR:1.80, 95CI%:1.44,2.27), 1.3-fold of all-cause long-term mortality (RR:1.33, 95CI%:1.19,1.48) and 1.2-fold of cardiovascular mortality (RR:1.19, 95CI%:1.04,1.36). Similar positive associations were also observed between hypokalemia and risk of all-cause mortality and cardiovascular mortality. The RRs of all-cause in-hospital, short-term, long-term mortality and cardiovascular mortality with hyperkalemia were attenuated to 2.21 (95CI%:1.60,3.06), 1.46(95CI%:1.25,1.71), 1.23 (95CI%:1.09,1.39) and 1.13 (95CI%:1.00,1.27) when treating hypokalemia together with normokalemia as the reference group. A U-shaped association was observed between potassium levels and mortality, with the lowest risk at around 4.2 mmol/L. Conclusions Both hypokalemia and hyperkalemia were positively associated with the risk of mortality in patients with CVD. Our results support the importance of potassium homeostasis for improving the CVD management. Registration PROSPERO, CRD42022324337.

Abstract Background Liver cancer remains a significant burden in Hong Kong. We sought to examine trends in liver cancer incidence using 30 years of cancer registry data in Hong Kong. Additionally, we aimed to assess the impact of age, period and birth cohort on liver cancer incidence, provided projections for liver cancer incidence until 2030, and examined the drivers of liver cancer incidence. Methods Data on liver cancer incidence were collected from the Hong Kong Cancer Registry (HKCaR). We assessed age, period, and birth cohort effects using age-period-cohort (APC) models. We employed Bayesian APC analysis with integrated nested Laplace approximations to project the future burden of liver cancer in Hong Kong. Furthermore, we attributed the changes in new liver cancer cases to population growth, population ageing, and epidemiological changes. Results The study included a total of 51,333 individuals, of whom 39,287 (76.53%) were male. From 1991 to 2020, the age-standardized liver cancer incidence rate in Hong Kong continued declining, while the number of new cases increased significantly, especially among males. The net drift, representing the overall annual percentage change of the age-adjusted rate, was − 3.06% (95% confidence interval [CI]: -3.31% to -2.80%) for males and − 3.85% (95% CI: -4.61% to -3.09%) for females. Local drift, which estimates the annual percentage change over time specific to age group, decreased in all age groups for both sexes, with a more pronounced decrease in younger age groups. The period and cohort risk of developing liver cancer also showed decreasing trends for both sexes. The study projected a decline in liver cancer cases for males but an increase for females in Hong Kong, with an estimated 1,083 cases in males and 710 cases in females by 2030. Demographic decomposition analysis revealed that while population growth and ageing were the main drivers of increased liver cancer cases, epidemiologic shifts mostly offset these factors. Conclusion The period and cohort risk of developing liver cancer in Hong Kong declined due to epidemiological changes. Although the age-standardized incidence rates of liver cancer have also declined, demographic and epidemiological factors have led to lower case expectations in males but a likely increase in females. Further research and epidemiological assessment of the disease are needed.

Abstract A patented strain of Bacillus amyloliquefaciens C-1 in our laboratory could produce functional sodium selenite (Na2SeO3) under optimized fermentation conditions. With the strong stress resistance and abundant secondary metabolites, C-1 showed potential to be developed as selenium-enriched postbiotics. C-1 has the ability to synthesize SeNPs when incubated with 100 μg/ml Na2SeO3 for 30 h at 30 °C aerobically with 10% seeds-culture. The transformation rate from Na2SeO3 into SeNPs reached to 55.51%. After selenium enrichment, there were no significant morphology changes in C-1 cells but obvious SeNPs accumulated inside of cells, observed by scanning electron microscope and transmission electron microscope, verified by energy dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy. SeNPs had antioxidant activity in radical scavenge of superoxide (O2 −), Hydroxyl radical (OH−) and 1,1-diphenyl-2-picryl-hydrazine (DPPH), where scavenging ability of OH− is the highest. Selenium-enriched C-1 had obvious anti-inflammatory effect in protecting integrity of Caco-2 cell membrane destroyed by S. typhimurium; it could preventing inflammatory damage in Caco-2 stressed by 200 μM H2O2 for 4 h, with significantly reduced expression of IL-8 (1.687 vs. 3.487, P = 0.01), IL-1β (1.031 vs. 5.000, P

IntroductionAn extended-spectrum beta-lactamase (ESBL)-hypervirulent Klebsiella pneumoniae (HvKP) strain HKE9 was isolated from the blood in an outpatient.MethodsThe effect of the global regulatory factor RpoS on antimicrobial resistance, pathogenicity, and environmental adaptability was elucidated.ResultsHKE9 is a novel ST3355 (K20/O2a) hypervirulent strain with a positive string test and resistant to cephems except cefotetan. It has a genome size of 5.6M, including two plasmids. CTX-M-15 was found in plasmid 2, and only ompk37 was found in the chromosome. HKE9 could produce bacterial siderophores, and genes of enterobactin, yersiniabactin, aerobactin, and salmochelin have been retrieved in the genome. As a global regulatory factor, knockout of rpoS did not change antimicrobial resistance or hemolytic phenotype while increasing the virulence to Galleria mellonella larvae and showing higher viscosity. Moreover, rpoS knockout can increase bacterial competitiveness and cell adhesion ability. Interestingly, HKE9-M-rpoS decreased resistance to acidic pH, high osmotic pressure, heat shock, and ultraviolet and became sensitive to disinfectants (H2O2, alcohol, and sodium hypochlorite). Although there were 13 Type 6 secretion system (T6SS) core genes divided into two segments with tle1 between segments in the chromosome, transcriptomic analysis showed that rpoS negatively regulated T4SS located on plasmid 2, type 1, and type 3 fimbriae and positively regulate genes responsible for acidic response, hyperosmotic pressure, heat shock, oxidative stress, alcohol and hypochlorous acid metabolism, and quorum sensing.DiscussionHere, this novel ST3355 ESBL-HvKP strain HKE9 may spread via various clonal types. The important regulation effect of rpoS is the enhanced tolerance and resistance to environmental stress and disinfectants, which may be at the cost of reducing virulence and regulated by T4SS.

Abstract Background Kashin–Beck disease (KBD) is a chronic, deforming, endemic osteochondropathy that begins in patients as young as 2–3 years of age. The pathogenesis of KBD remains unclear, although selenium (Se) deficiency and T-2 toxin food contamination are both linked to the disease. In the present study, we evaluated transforming growth factor-β receptor (TGF-βR I and II) levels in clinical samples of KBD and in pre-clinical disease models. Methods Human specimens were obtained from the hand phalanges of eight donors with KBD and eight control donors. Animal models of the disease were established using Sprague–Dawley rats, which were fed an Se-deficient diet for 4 weeks and later administered the T-2 toxin. Cartilage cellularity and morphology were examined by hematoxylin and eosin staining. Expression and localization of TGF-βRI and II were evaluated using immunohistochemical staining and western blotting. Results In the KBD samples, chondral necrosis was detected based on cartilage cell disappearance and alkalinity loss in the matrix ground substance. In the necrotic areas, TGF-βRI and II staining were strong. Positive percentages of TGF-βRI and II staining were higher in the cartilage samples of KBD donors than in those of control donors. TGF-βRI and II staining was also increased in cartilage samples from rats administered T-2 toxin or fed on Se-deficient plus T-2 toxin diets. Conclusion TGF-βRI and II may be involved in the pathophysiology of KBD. This study provides new insights into the pathways that contribute to KBD development.

Dysregulation of lipid metabolism has been implicated in age-related macular degeneration (AMD), the leading cause of blindness among the elderly. Lecithin cholesterol acyltransferase (LCAT) is an important enzyme responsible for lipid metabolism, which could be regulated by DNA methylation during the development of various age-related diseases. This study aimed to assess the association between LCAT DNA methylation and the risk of AMD, and to examine whether plasma vitamin and carotenoid concentrations modified this association. A total of 126 cases of AMD and 174 controls were included in the present analysis. LCAT DNA methylation was detected by quantitative real-time methylation-1specific PCR (qMSP). Circulating vitamins and carotenoids were measured using reversed-phase high-performance liquid chromatography (RP-HPLC). DNA methylation of LCAT was significantly higher in patients with AMD than those in the control subjects. After multivariable adjustment, participants in the highest tertile of LCAT DNA methylation had a 5.37-fold higher risk (95% CI: 2.56, 11.28) of AMD compared with those in the lowest tertile. Each standard deviation (SD) increment of LCAT DNA methylation was associated with a 2.23-fold (95% CI: 1.58, 3.13) increased risk of AMD. There was a J-shaped association between LCAT DNA methylation and AMD risk (Pnon-linearity = 0.03). Higher concentrations of plasma retinol and β-cryptoxanthin were significantly associated with decreased levels of LCAT DNA methylation, with the multivariate-adjusted β coefficient being −0.05 (95% CI: −0.08, −0.01) and −0.25 (95% CI: −0.42, −0.08), respectively. In joint analyses of LCAT DNA methylation and plasma vitamin and carotenoid concentrations, the inverse association between increased LCAT DNA methylation and AMD risk was more pronounced among participants who had a lower concentration of plasma retinol and β-cryptoxanthin. These findings highlight the importance of comprehensively assessing LCAT DNA methylation and increasing vitamin and carotenoid status for the prevention of AMD.

Previous research has suggested that high serum ferritin (SF) levels may be associated with dyslipidemia. This study investigated the association between SF levels and dyslipidemia in American adults, which held relevance for both clinical and public health areas concerned with screening and prevention. Data from the pre-pandemic National Health and Nutrition Examination Surveys (NHANES), conducted between 2017 and 2020, were utilized for this analysis. Multivariate linear regression models were used to explore the correlation between lipid and SF concentrations, and the connection between SF and the four types of dyslipidemia was further assessed by using multivariate logistic regression analysis. Odds ratios (ORs; 95% CI) for dyslipidemia were calculated for quartiles of SF concentrations, with the lowest ferritin quartile as the reference. The final subjects consisted of 2676 participants (1290 males and 1386 females). ORs for dyslipidemia were the highest in the fourth quartile (Q4) of SF both in males (OR: 1.60, 95% CI: 1.12–2.28) and females (OR: 1.52, 95% CI: 1.07–2.17). The crude ORs (95% CI) for the risk of High TC and High LDL-C increased progressively in both genders. However, after adjusting for covariates, the trend of significance was only present in females. Finally, the association between total daily iron intake and the four types of dyslipidemia was examined, revealing that the risk of High TG in the third quartile of the total daily iron intake was 2.16 times greater in females (adjusted OR: 3.16, 95% CI: 1.38–7.23). SF concentrations were remarkably associated with dyslipidemia. In females, daily dietary iron intake was associated with High-TG dyslipidemia.

Ni–Mn–In magnetic shape memory alloys, which can be stimulated by an external magnetic field, exhibit a fast response and have aroused wide attention in the field of electro-mechanical actuators. However, the low working temperature and the inherent brittleness severely limit their application scenarios. Here, an effective strategy is proposed to improve the magnetic-field-induced working temperature and mechanical properties in Ni–Mn–In shape memory alloys. We predict that the Ni16Mn12In4 alloy with Pt doping can solve the problems simultaneously through a comprehensive first-principles study. The calculations show that Pt occupying Ni sites can increase the martensitic temperature (TM) and Curie temperature (TC) simultaneously. TM and TC of Ni14Mn12In4Pt2 are predicted to be as high as 440 and 476 K, respectively. This is mainly due to the increased phase stability of the martensite and Pt–Mn bonds having stronger ferromagnetic exchange effects than Ni–Mn bonds after Pt doping. Moreover, according to the increase of B/G and v after Pt doping, it can be concluded that the mechanical properties of the alloy have been improved.

Background: Hypertension (HTN), dyslipidemia and hyperhomocysteinemia (HHcy) are risk factors for cardiovascular disease (CVD). Methods: Hypertensive Chinese subjects (n = 228) were enrolled. MTHFR C667T, MTHFR A1298C, MTR A2756G, and MTRR A66G genotypes were determined. Unconditional logistic regression was performed to determine the associations of serum Hcy status and genotypes with HTN and dyslipidemia. Results: The mean age of hypertensive adults was 65.53 ± 9.94 years, including 88 (38.6%) men and 140 (61.4%) women. Patients with MTHFR 667TT and MTRR GG carriers showed higher serum Hcy levels (P = 0.019 and 0.018, respectively), which is associated with higher serum triacylglycerols (TAG) and total cholesterol (TC) levels (P = 0.014 and 0.044, respectively) and a higher risk for hypertriglyceridemia (OR = 1.889, 95% CI: 1.105–3.229, P = 0.020). Compared with low Hcy and MTRR 66AA, those with high Hcy and 66AA or 66AG+GG showed higher odd\s of hypertriglyceridemia (MTRR 66AA+ high Hcy: OR: 2.692, 95% CI: 1.189–6.096, Pcombined = 0.018; MTRR 66AG/GG+ high Hcy: OR: 3.433, 95% CI: 1.517–7.772, Pcombined = 0.003, respectively). Patients with high Hcy and MTHFR 667CC, as well as those with low Hcy and 667CT+TT, showed lower odds of uncontrolled SBP (MTHFR 667CC+ high Hcy: OR: 0.338, 95% CI: 0.115–0.996, Pcombined = 0.049; MTHFR 667CT/TT+ low Hcy: OR: 0.421, 95% CI: 0.193–0.921, Pcombined = 0.030) compared to patients with low Hcy and MTHFR 667CC. Conclusions: Serum Hcy status and Hcy metabolism gene polymorphisms (MTHFR C667T and MTRR A66G) may have synergistic effects on the prevalence of HTN and dyslipidemia.

Ni-Mn-Sn ferromagnetic shape memory alloys, which can be stimulated by an external magnetic field, exhibit a fast response and have aroused wide attention. However, the fixed and restricted working temperature range has become a challenge in practical application. Here, we introduced strain engineering, which is an effective strategy to dynamically tune the broad working temperature region of Ni-Co-Mn-Sn alloys. The influence of biaxial strain on the working temperature range of Ni-Co-Mn-Sn alloy was systematically investigated by the ab initio calculation. These calculation results show a wide working temperature range (200 K) in Ni14Co2Mn13Sn3 FSMAs can be achieved with a slight strain from 1.5% to −1.5%, and this wide working temperature range makes Ni14Co2Mn13Sn3 meet the application requirements for both low-temperature and high-temperature (151–356 K) simultaneously. Moreover, strain engineering is demonstrated to be an effective method of tuning martensitic transformation. The strain can enhance the stability of the Ni14Co2Mn13Sn3 martensitic phase. In addition, the effects of strain on the magnetic properties and the martensitic transformation are explained by the electronic structure in Ni14Co2Mn13Sn3 FSMAs.

Maternal obesity or exposure to a high-fat diet (HFD) has an irreversible impact on the structural and functional development of offspring brains. This study aimed to investigate whether maternal HFD during pregnancy and lactation impairs dentate gyrus (DG) neurogenesis in offspring by altering neural stem cells (NSCs) behaviors. Pregnant Sprague-Dawley rats were fed a chow diet (CHD) or HFD (60% fat) during gestation and lactation. Pups were collected on postnatal day 1 (PND 1), PND 10 and PND 21. Changes in offspring body weight, brain structure and granular cell layer (GCL) thickness in the hippocampus were analyzed. Hippocampal NSCs behaviors, in terms of proliferation and differentiation, were investigated after immunohistochemical staining with Nestin, Ki67, SOX2, Doublecortin (DCX) and NeuN. Maternal HFD accelerated body weight gain and brain structural development in offspring after birth. It also reduced the number of NSCs and their proliferation, leading to a decrease in NSCs pool size. Furthermore, maternal HFD intensified NSCs depletion and promoted neuronal differentiation in the early postnatal development period. These findings suggest that maternal HFD intake significantly reduced the amount and capability of NSCs via reducing type–2 NSCs and promoting premature neuronal differentiation during postnatal hippocampal development.

A crucial point of restricting its development and application is the lack of dynamically tunable devices in the terahertz fields. In this work, shape memory alloys (SMAs) are innovatively introduced into the design of THz metamaterials absorber (MMA). An optimized structure design is proposed, and the MMA exhibits the perfect properties of dynamical tuning, polarization insensitivity, and dual-band absorption. In detail, two discrete resonance peaks can be detected, and their corresponding absorbance is up to 98.8% at 0.9982 THz and 96.8% at 1.5328 THz, respectively. The effect of structural parameters on the absorption performance is investigated further to reveal these two peaks' formation mechanism. Based on the martensitic transformation of TiNi alloy, the absorption peaks can be dynamically tuned to the desired operating frequencies through varying the external thermal field. Meanwhile, the absorber is polarization-insensitive when it is incident vertically due to the symmetry of the structure, and the excellent absorption performance can be maintained over a wide angular range of incidence. On account of the ultra-narrow bandwidth and the high-quality factor Q, we discuss the sensing ability of peak B. It can be found that peak B is sensitive to a minor change of the refractive index n of surrounding media and shows sensing ability. Through theoretical analysis, the sensitivity of the sensor is up to 0.88 THz/RIU, and the sensor’s figure of merit can be up to 92.63. This work proposes a novel idea of the design of various SMAs-based dynamically tunable terahertz optical devices.

Nanocarriers encapsulating multiple chemotherapeutics are a promising strategy to achieve combinational chemotherapy for cancer therapy; however, they generally use exotic new carriers without therapeutic effect, which usually suffer from carrier-related toxicity issues, as well as having to pass extensive clinical trials to be drug excipients before any clinical applications. Cargo-free nanomedicines, which are fabricated by drugs themselves without new excipients and possess nanoscale characteristics to realize favorable pharmacokinetics and intracellular delivery, have been rapidly developed and drawn much attention to cancer treatment. Herein, we discuss recent advances of cargo-free nanomedicines for cancer treatment. After a brief introduction to the major types of carrier-free nanomedicine, some representative applications of these cargo-free nanomedicines are discussed, including combination therapy, immunotherapy, as well as self-monitoring of drug release. More importantly, this review draws a brief conclusion and discusses the future challenges of cargo-free nanomedicines from our perspective.

The cross-talk between hepatocellular carcinoma (HCC) cells and activated hepatic stellate cells (HSCs) is considered to be important for modulating the biological behavior of tumor cells. However, the molecular links between inflammation and cancer in the activation of HSCs remain to be elucidated. The present study demonstrated that cluster of differentiation (CD)147 is a key molecule involved in the interaction between HCC cells and HSCs. The effects of conditioned medium from human HCC cells on the activation of the human HSC line, LX-2, were assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Western blotting, RT-qPCR and gelatin zymography were also used to investigate the effects of CD147 on the activation of LX-2. The expression levels of α-smooth muscle actin (α-SMA) and CD147 were assessed in a co-culture system of LX-2 and FHCC-98 cells by immunofluorescence staining and immunoblotting. In hepatic tissues from a rat model of fibrosis, immunohistochemistry and immunoblotting were performed to detect the expression levels of α-SMA and CD147. Tumor-conditioned medium and CD147 promoted cell proliferation, activated LX-2 cells, increased the expression levels of α-SMA, collagen I and tissue inhibitor of metalloproteinase-1 (TIMP-1), and increased the secretion of matrix metalloproteinase (MMP)-2. The HSCs, which were induced in the co-culture system of HCC cells and HSCs exhibited marked expression levels of CD147. In the hepatic tissue of rat models of fibrosis induced by CCl4, marked expression levels of CD147 were observed in the activated HSCs. Therefore, CD147 promoted the activation of HSCs and was a key molecule during HCC cell-HSC cross-talk in the rat liver. [ABSTRACT FROM AUTHOR]