China has pledged to peak carbon emissions before 2030 and strive to achieve carbon neutrality before 2060. However, the significant variations of provincial carbon emissions make it unclear whether ...they can jointly fulfill the national carbon peak and neutrality goal. Thus, this study predicts the emission trajectories at provincial level in China by employing the extended STIRPAT (Stochastic Impacts by Regression on Population, Affluence, and Technology) model to see the feasibility and time of reaching peak carbon emissions and carbon neutrality. We found that most provinces can achieve peak emission before 2030 but challenging to achieve carbon neutrality before 2060, even considering the ecological carbon sink. The provincial neutrality time is concentrated between 2058 and 2070; the sooner the carbon emission peaks, the earlier the carbon neutral will be realized. The aggregated carbon emissions at provincial level show that China can achieve its carbon emission peak of 9.64–10.71 Gt before 2030, but it is unlikely to achieve the carbon neutrality goal before 2060 without carbon capture, utilization, and storage (CCUS). With high CCUS development, China is expected to achieve carbon neutrality in 2054–2058, irrespective of the socio-economic scenarios. With low CCUS development, China's carbon neutrality target will be achieved only under the accelerated-improvement scenario, while it will postpone to 2061 and 2064 under the continued-improvement and the business-as-usual scenarios, respectively.
The pandemic of coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has caused an unprecedented global social and economic impact, and ...high numbers of deaths. Many risk factors have been identified in the progression of COVID‐19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID‐19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high‐sensitivity C‐reactive protein, proinflammatory cytokines such as interleukin (IL)‐6, IL‐1β, Krebs von den Lungen‐6 (KL‐6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID‐19.
Globally, liver cancer, which is one of the major cancers worldwide, has attracted the growing attention of technological researchers for its high mortality and limited treatment options. Hydrogels ...are soft 3D network materials containing a large number of hydrophilic monomers. By adding moieties such as nitrobenzyl groups to the network structure of a cross‐linked nanocomposite hydrogel, the click reaction improves drug‐release efficiency in vivo, which improves the survival rate and prolongs the survival time of liver cancer patients. The application of a nanocomposite hydrogel drug delivery system can not only enrich the drug concentration at the tumor site for a long time but also effectively prevents the distant metastasis of residual tumor cells. At present, a large number of researches have been working toward the construction of responsive nanocomposite hydrogel drug delivery systems, but there are few comprehensive articles to systematically summarize these discoveries. Here, this systematic review summarizes the synthesis methods and related applications of nanocomposite responsive hydrogels with actions to external or internal physiological stimuli. With different physical or chemical stimuli, the structural unit rearrangement and the controlled release of drugs can be used for responsive drug delivery in different states.
Cross‐linked hydrophilic polymer chains that can form gels are widely utilized for biomedical applications, such as drug delivery. Various studies have also demonstrated the effects of particle size and surface morphology on drug release from particles in liver cancer therapy. Mechanistic understandings of responsive hydrogels in responsive stimuli are provided, by which better clinical choices may be approached.
LINKED CONTENT
This article is linked to Toyoda et al papers. To view these articles, visit https://doi.org/10.1111/apt.17088 and https://doi.org/10.1111/apt.17139
Although clinical studies have shown promise for targeting programmed cell death protein-1 (PD-1) and ligand (PD-L1) signaling in non-small cell lung cancer (NSCLC), the factors that predict which ...subtype patients will be responsive to checkpoint blockade are not fully understood.
We performed an integrated analysis on the multiple-dimensional data types including genomic, transcriptomic, proteomic, and clinical data from cohorts of lung adenocarcinoma public (discovery set) and internal (validation set) database and immunotherapeutic patients. Gene set enrichment analysis (GSEA) was used to determine potentially relevant gene expression signatures between specific subgroups.
We observed that
mutation significantly increased expression of immune checkpoints and activated T-effector and interferon-γ signature. More importantly, the
comutated subgroup manifested exclusive increased expression of PD-L1 and a highest proportion of
Meanwhile,
or
-mutated tumors showed prominently increased mutation burden and specifically enriched in the transversion-high (TH) cohort. Further analysis focused on the potential molecular mechanism revealed that
or
mutation altered a group of genes involved in cell-cycle regulating, DNA replication and damage repair. Finally, immunotherapeutic analysis from public clinical trial and prospective observation in our center were further confirmed that
or
mutation patients, especially those with co-occurring
mutations, showed remarkable clinical benefit to PD-1 inhibitors.
This work provides evidence that
and
mutation in lung adenocarcinoma may be served as a pair of potential predictive factors in guiding anti-PD-1/PD-L1 immunotherapy.
.
Background
Cancer stem cells (CSCs) are responsible for drug resistance, cancer relapse, and metastasis. Here, we report the first analysis of Palladin expression and its impacts on stem cell‐like ...properties in lung cancer.
Methods
Tissue microarrays were used to investigate Palladin expression and its association with prognosis. Immunofluorescence (IF), flow fluorescence assay, and Western blot were performed to detect Palladin expression in 6 NSCLC cell lines. Cell phenotypes and drug resistance were evaluated. Xenograft models were constructed to confirm the role of Palladin in vivo.
Results
By using the tissue microarrays, Palladin was identified to be highly expressed in the cytoplasm, specifically in the cytomembrane of NSCLC, and its high expression is associated with poor prognosis. Palladin is widely expressed and enriched in the sphere cells. The in vitro and in vivo studies showed that Palladin promoted stem cell‐like properties, including cell viability, invasion, migration, self‐renewal abilities, taxol resistance, and tumorigenicity. Western blot revealed that Palladin promoted the accumulation of β‐catenin and activated Wnt/β‐catenin signaling. Tissue microarrays analysis further confirmed the positive correlation between Palladin and β‐catenin. Wnt/β‐catenin pathway inhibitor blocked the Palladin‐induced enhancement of sphere‐forming.
Conclusions
Palladin might act as an oncogene by promoting CSCs‐like properties and tumorigenicity of NSCLC cells via the Wnt/β‐catenin signaling pathway. Besides, Palladin was identified to have the potential as a cell surface marker for LCSCs identification. These findings provide a possible target for developing putative agents targeted to LCSCs.
Palladin was identified to be specifically expressed in the cytomembrane of patients with NSCLC, suggesting its potential as a cell surface marker for LCSCs identification. More importantly, we demonstrated that Palladin might serve as a tumor oncogene and promote the biological properties of LCSCs, possibly by activating the Wnt/β‐catenin signaling in NSCLC for the first time. The elucidation of this new molecular mechanism for Palladin and Wnt/β‐catenin signaling activation is conducive to understand the pathogenesis of NSCLC, providing a novel possibility of the development of novel therapeutic target for CSCs targeted therapy.
The lateral parabrachial nucleus (LPBN) is known to relay noxious information to the amygdala for processing affective responses. However, it is unclear whether the LPBN actively processes ...neuropathic pain characterized by persistent hyperalgesia with aversive emotional responses. Here we report that neuropathic pain-like hypersensitivity induced by common peroneal nerve (CPN) ligation increases nociceptive stimulation-induced responses in glutamatergic LPBN neurons. Optogenetic activation of GABAergic LPBN neurons does not affect basal nociception, but alleviates neuropathic pain-like behavior. Optogenetic activation of glutamatergic or inhibition of GABAergic LPBN neurons induces neuropathic pain-like behavior in naïve mice. Inhibition of glutamatergic LPBN neurons alleviates both basal nociception and neuropathic pain-like hypersensitivity. Repetitive pharmacogenetic activation of glutamatergic or GABAergic LPBN neurons respectively mimics or prevents the development of CPN ligation-induced neuropathic pain-like hypersensitivity. These findings indicate that a delicate balance between excitatory and inhibitory LPBN neuronal activity governs the development and maintenance of neuropathic pain.
A novel fast-diagnostic method for open-switch faults in inverters without sensors is proposed to improve the reliability of power electronic system in this paper. The presented method is achieved by ...analysis of switching function model of the inverter under both healthy and faulty conditions. Due to the different voltages endured by each power switch under healthy condition from open-switch faults in some cases, open-circuit faults can be detected by sensing the collector-emitter voltages of the lower power switches in each leg. The diagnostic scheme employs the simple hardware circuit to obtain indirectly the voltages of lower power switches and to get rid of high cost and complexity as a result of sensors. Also, this method minimizes the detection time and is available for the inverter faults in the systems with open-loop or closed-loop current control strategies. To ensure the effectiveness and reliability of the proposed diagnostic method, the rising-edge delays for switching signals are used to avoid misdiagnostic results because of the ON-OFF processes of power switches, and the delay durations are determined considering various factors. Simulation and experimental results validate the proposed scheme for detecting switch and leg open-circuit faults.
•Fever and cough are the most common symptoms in patients with COVID-19.•The most prevalent comorbidities are hypertension and diabetes which are associated with the severity of COVID-19.•ARDS and ...ACI may be the main obstacles to treatment recovery for patients.•The case severe rate and mortality is lower than that of SARS and MERS.
Since being first reported in Wuhan, China, in December 8, 2019, the outbreak of the novel coronavirus, now known as COVID-19, has spread globally. Some case studies regarding the characteristics and outcome of patients with COVID-19 have been published recently. We conducted a meta-analysis to evaluate the risk factors of COVID-19.
Medline, SinoMed, EMBASE, and Cochrane Library were searched for clinical and epidemiological studies on confirmed cases of COVID-19.
The incidence of fever, cough, fatigue, and dyspnea symptoms were 85.6 % (95CI 81.3–89.9 %), 65.7 % (95CI 60.1–71.4 %), 42.4 % (95CI 32.2–52.6 %) and 21.4 % (95CI 15.3–27.5 %). The prevalence of diabetes was 7.7 % (95CI 6.1–9.3 %), hypertension was 15.6 % (95CI 12.6–18.6 %), cardiovascular disease was 4.7 % (95CI 3.1–6.2 %), and malignancy was 1.2 % (95CI 0.5–1.8 %). The complications, including ARDS risk, ranged from 5.6–13.2 %, with the pooled estimate of ARDS risk at 9.4 %, ACI at 5.8 % (95CI 0.7–10.8 %), AKI at 2.1 % (95CI 0.6–3.7 %), and shock at 4.7 % (95CI 0.9–8.6 %). The risks of severity and mortality ranged from 12.6 to 23.5% and from 2.0 to 4.4 %, with pooled estimates at 18.0 and 3.2 %, respectively. The percentage of critical cases in diabetes and hypertension was 44.5 % (95CI 27.0–61.9 %) and 41.7 % (95CI 26.4–56.9 %), respectively.
Fever is the most common symptom in patients with COVID-19. The most prevalent comorbidities are hypertension and diabetes which are associated with the severity of COVID-19. ARDS and ACI may be the main obstacles for patients to treatment recovery. The case severe rate and mortality is lower than that of SARS and MERS.
Abstract
Background
Circular RNA (circRNAs) and hypoxia have been found to play the key roles in the pathogenesis and progression of cancer including colorectal cancer (CRC). However, the expressions ...and functions of the specific circRNAs in regulating hypoxia-involved CRC metastasis, and the circRNAs that are relevant to regulate HIF-1α levels in CRC remain elusive.
Methods
qRT-PCR was used to detect the expression of circRNAs and mRNA in CRC cells and tissues. Fluorescence in situ hybridization (FISH) was used to analyze the location of circ-ERBIN. Function-based experiments were performed using circ-ERBIN overexpression and knockdown cell lines in vitro and in vivo, including CCK8, colony formation, EdU assay, transwell, tumor growth and metastasis models. Mechanistically, luciferase reporter assay, western blots and immunohistochemical stainings were performed.
Results
Circ-Erbin was highly expressed in the CRC cells and Circ-Erbin overexpression facilitated the proliferation, migration and metastasis of CRC in vitro and in vivo. Notably, circ-Erbin overexpression significantly promoted angiogenesis by increasing the expression of hypoxia induced factor (HIF-1α) in CRC. Mechanistically, circ-Erbin accelerated a cap-independent protein translation of HIF-1α in CRC cells as the sponges of miR-125a-5p and miR-138-5p, which synergistically targeted eukaryotic translation initiation factor 4E binding protein 1(4EBP-1).
Conclusions
Our findings uncover a key mechanism for circ-Erbin mediated HIF-1α activation by miR-125a-5p-5p/miR-138-5p/4EBP-1 axis and circ-ERBIN is a potential target for CRC treatment.
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