Cardiovascular disease (CVD) and environmental degradation are leading global health problems of our time. Recent studies have linked exposure to heavy metals to the risks of CVD and diabetes, ...particularly in populations from low- and middle-income countries, where concomitant rapid development occurs. In this review, we 1) assessed the totality, quantity, and consistency of the available epidemiological studies, linking heavy metal exposures to the risk of CVD (including stroke and coronary heart disease); 2) discussed the potential biological mechanisms underlying some tantalizing observations in humans; and 3) identified gaps in our knowledge base that must be investigated in future work. An accumulating body of evidence from both experimental and observational studies implicates exposure to heavy metals, in a dose-response manner, in the increased risk of CVD. The limitations of most existing studies include insufficient statistical power, lack of comprehensive assessment of exposure, and cross-sectional design. Given the widespread exposure to heavy metals, an urgent need has emerged to investigate these putative associations of environmental exposures, either independently or jointly, with incident CVD outcomes prospectively in well-characterized cohorts of diverse populations, and to determine potential strategies to prevent and control the impacts of heavy metal exposure on the cardiometabolic health outcomes of individuals and populations.
Although progress has been made to improve photocatalytic CO2 reduction under visible light (λ>400 nm), the development of photocatalysts that can work under a longer wavelength (λ>600 nm) remains a ...challenge. Now, a heterogeneous photocatalyst system consisting of a ruthenium complex and a monolayer nickel‐alumina layered double hydroxide (NiAl‐LDH), which act as light‐harvesting and catalytic units for selective photoreduction of CO2 and H2O into CH4 and CO under irradiation with λ>400 nm. By precisely tuning the irradiation wavelength, the selectivity of CH4 can be improved to 70.3 %, and the H2 evolution reaction can be completely suppressed under irradiation with λ>600 nm. The photogenerated electrons matching the energy levels of photosensitizer and m‐NiAl‐LDH only localized at the defect state, providing a driving force of 0.313 eV to overcome the Gibbs free energy barrier of CO2 reduction to CH4 (0.127 eV), rather than that for H2 evolution (0.425 eV).
The selectivity of CH4 reached 70.3 % and the by‐product H2 was completely suppressed by monolayer‐NiAl‐LDH in CO2 photoreduction under irradiation with λ>600 nm. The defect state in monolayer‐NiAl‐LDH plays an important role in the outstanding selectivity by localizing the photogenerated electrons excited by photons with λ>600 nm.
The precise and large-scale identification of intact glycopeptides is a critical step in glycoproteomics. Owing to the complexity of glycosylation, the current overall throughput, data quality and ...accessibility of intact glycopeptide identification lack behind those in routine proteomic analyses. Here, we propose a workflow for the precise high-throughput identification of intact N-glycopeptides at the proteome scale using stepped-energy fragmentation and a dedicated search engine. pGlyco 2.0 conducts comprehensive quality control including false discovery rate evaluation at all three levels of matches to glycans, peptides and glycopeptides, improving the current level of accuracy of intact glycopeptide identification. The N-glycoproteome of samples metabolically labeled with
N/
C were analyzed quantitatively and utilized to validate the glycopeptide identification, which could be used as a novel benchmark pipeline to compare different search engines. Finally, we report a large-scale glycoproteome dataset consisting of 10,009 distinct site-specific N-glycans on 1988 glycosylation sites from 955 glycoproteins in five mouse tissues.Protein glycosylation is a heterogeneous post-translational modification that generates greater proteomic diversity that is difficult to analyze. Here the authors describe pGlyco 2.0, a workflow for the precise one step identification of intact N-glycopeptides at the proteome scale.
Key message
Cytokinins are a class of phytohormone that participate in the regulation of the plant growth, development, and stress response. In this review, the potential regulating mechanism during ...plant growth and stress response are discussed.
Cytokinins are a class of phytohormone that participate in the regulation of plant growth, physiological activities, and yield. Cytokinins also play a key role in response to abiotic stresses, such as drought, salt and high or low temperature. Through the signal transduction pathway, cytokinins interact with various transcription factors via a series of phosphorylation cascades to regulate cytokinin-target gene expression. In this review, we systematically summarize the biosynthesis and metabolism of cytokinins, cytokinin signaling, and associated gene regulation, and highlight the function of cytokinins during plant development and resistance to abiotic stress. We also focus on the importance of crosstalk between cytokinins and other classes of phytohormones, including auxin, ethylene, strigolactone, and gibberellin. Our aim is to provide a comprehensive overview of recent findings on the mechanisms by which cytokinins act as central regulators of plant development and stress reactions, and highlight topics for future research.
The lack of broad‐spectrum tumor antigens, limited immunogenicity of antigens, and immunosuppressive microenvironment in tumors have impeded the development of cancer vaccines. To address this issue, ...a vaccine platform is developed based on Spirulina skeleton fibers loaded with gold (Au) nanoparticles (Au@E‐SP). Upon subcutaneous administration, Au@E‐SP self‐aggregates in situ and forms a 3D vaccine scaffold owing to its elongated and helical architecture. Through the aggregation of Au@E‐SP, Au nanoparticles are concentrated, which significantly enhances the local photothermal effect and releases more tumor‐associated antigens. In addition, the retained E‐SP serves as a natural immune adjuvant that sustainably reverses the immunosuppressive microenvironment in vivo. Combining these advantages, the vaccines induce a potent anti‐tumor immune response, effectively inhibiting tumor recurrence and metastasis. This strategy utilizes microalgae as a self‐adjuvant vaccine, providing a promising avenue for further research in tumor immunotherapy.
The study reports on the use of a vaccine platform loaded with gold (Au) nanoparticles in the Spirulina skeleton fibers (Au@E‐SP) to enhance the efficacy of thermal immunotherapy. Au@E‐SP is capable of spontaneously aggregating in situ and forming a 3D vaccine scaffold upon subcutaneous administration for effective inhibition of tumor recurrence and metastasis.
Immunotherapy has provided a promising strategy for the treatment of cancers. However, even in tumors with high antigen burdens, the systemic inhibition of the antigen presentation still greatly ...restricts the application of immunotherapy. Here, we construct a tumor protein-engineering system based on the functional tripeptide, Asp-Phe-Tyr (DFY), which can automatically collect and deliver immunogenetic tumor proteins from targeted cells to immune cells. Through a tyrosinase-catalyzed polymerization, the DFY tripeptide selectively accumulates in tyrosinase high-expressed melanoma cells. Then quinone-rich intermediates are covalently linked with tumor-specific proteins by Michael addition and form tumor protein-carried microfibers that could be engulfed by antigen-presenting cells and exhibited tumor antigenic properties for boosting immune effect. In melanoma cells with deficient antigen presentation, this system can successfully enrich and transport tumor antigen-containing proteins to immune cells. Furthermore, in the in vivo study on murine melanoma, the transdermal delivery of the DFY tripeptide suppressed the tumor growth and the postsurgery recurrence. Our findings provide an avenue for the regulation of the immune system on an organism by taking advantage of certain polymerization reactions by virtue of chemical biology.
Dual-band bandpass filters using novel stub-loaded resonators (SLRs) are presented in this letter. Characterized by both theoretical analysis and full-wave simulation, the proposed SLR is found to ...have the advantage that the even-mode resonant frequencies can be flexibly controlled whereas the odd-mode resonant frequencies are fixed. Based on the proposed SLR, a dual-band filter is implemented with three transmission zeros. To further improve the selectivity, a filter with four transmission zeros on either side of both passbands is designed by introducing spur-line. The measured results validate the proposed design.
Background
Diagnostic criteria for sarcopenia have not been established in Chinese. This study established criteria based on the L3‐skeletal muscle index (L3‐SMI) and assessed its value for outcomes ...predicting in cirrhotic Chinese patients.
Methods
Totally 911 subjects who underwent a CT scan at two centres were enrolled in Cohort 1 (394 male and 417 female subjects, aged 20–80 years). The data of those subjects younger than 60 years (365 male and 296 female subjects) were used to determine the reference intervals of the L3‐SMI and its influencing factors. Cohort 2 consisted of 480 patients (286 male and 184 female patients) from three centres, and their data were used to investigate the prevalence of sarcopenia and evaluate the value of L3‐SMI for predicting the prognosis and complications of cirrhosis.
Results
Age and sex had the greatest effects on the L3‐SMI (P < 0.001). The L3‐SMI scores were clearly higher in male patients than in female patients (52.94 ± 8.41 vs. 38.91 ± 5.65 cm2/m2, P < 0.001) and sharply declined in subjects aged ≥ 60 years. Based on the mean −1.28 × SD among adults aged < 60 years, the L3‐SMI cut‐off value for sarcopenia was 44.77 cm2/m2 in male patients and 32.50 cm2/m2 in female patients. Using these values, 22.5% of the cirrhotic patients (28.7% of male patients and 11.9% of female patients) were diagnosed with sarcopenia. Compared with non‐sarcopenia individuals, sarcopenia patients had lower body mass index (21.28 ± 3.01 vs. 24.09 ± 3.39 kg/m2, P < 0.001) and serum albumin levels (31.54 ± 5.93 vs. 32.93 ± 5.95 g/L, P = 0.032), longer prothrombin times (16.39 ± 3.05 vs. 15.71 ± 3.20 s, P = 0.049), higher total bilirubin concentrations (41.33 ± 57.38 vs. 32.52 ± 31.48 μmol/L, P = 0.039), worse liver function (Child–Pugh score, 8.05 ± 2.11 vs. 7.32 ± 2.05, P = 0.001), higher prevalence of cirrhosis‐related complications (81.82% vs. 62.24%, P < 0.001) and mortality (30.68% vs. 11.22%, P < 0.001). Overall survival was significantly lower in the sarcopenia group risk ratio (RR) = 2.643, 95% confidence interval (CI) 1.646–4.244, P < 0.001, accompanied with an increased cumulative incidence of ascites (RR = 1.827, 95% CI 1.259–2.651, P = 0.002), spontaneous bacterial peritonitis (RR = 3.331, 95% CI 1.404–7.903, P = 0.006), hepatic encephalopathy (RR = 1.962, 95% CI 1.070–3.600, P = 0.029), and upper gastrointestinal varices (RR = 2.138, 95% CI 1.319–3.466, P = 0.002). Subgroup analysis showed sarcopenia shortened the survival of the patients with Model For End‐Stage Liver Disease score > 14 (RR = 4.310, 95% CI 2.091–8.882, P < 0.001) or Child–Pugh C (RR = 3.081, 95% CI 1.516–6.260, P = 0.002).
Conclusions
Sarcopenia is a common comorbidity of cirrhosis and can be used to predict cirrhosis‐related complications and the prognosis.
Proteolysis targeting chimeric (PROTAC) technology is an effective endogenous protein degradation tool developed in recent years that can ubiquitinate the target proteins through the ...ubiquitin-proteasome system (UPS) to achieve an effect on tumor growth. A number of literature studies on PROTAC technology have proved an insight into the feasibility of PROTAC technology to degrade target proteins. Additionally, the first oral PROTACs (ARV-110 and ARV-471) have shown encouraging results in clinical trials for prostate and breast cancer treatment, which inspires a greater enthusiasm for PROTAC research. Here we focus on the structures and mechanisms of PROTACs and describe several classes of effective PROTAC degraders based on E3 ligases.
Renal cell carcinoma (RCC) is a common kidney cancer worldwide. Even though current treatments show promising therapeutic effectiveness, metastatic RCC still has limited therapeutic options so that ...novel treatments were urgently needed. Here, we identified that MUC12 was overexpressed in RCC patients and served as poor prognostic factor for RCC progression. Overexpression of MUC12 increased RCC cell growth and cell invasion while deficiency of MUC12 exerted opposite effects on RCC cells. Mechanistic dissection demonstrated that MUC12‐mediated RCC cell growth and cell invasion were dependent of TGF‐β1 signalling because they could be blocked in the presence of TGF‐β1 inhibitor. Moreover, the regulation of TGF‐β1 by MUC12 relied on the transactivation of c‐Jun. MUC12 promoted the recruitment of c‐Jun on the promoter of TGF‐β1, leading to its transcription. Importantly, knockdown of c‐Jun also attenuated MUC12‐mediated TGF‐β1 induction and RCC cell invasion. In summary, our study defines the role of MUC12 in RCC progression and provides rational to develop novel targeted therapy to battle against RCC.
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