Vertical cavity surface-emitting lasers (VCSELs) have made indispensable contributions to the development of modern optoelectronic technologies. However, arbitrary beam shaping of VCSELs within a ...compact system has remained inaccessible until now. The emerging ultra-thin flat optical structures, namely metasurfaces, offer a powerful technique to manipulate electromagnetic fields with subwavelength spatial resolution. Here, we show that the monolithic integration of dielectric metasurfaces with VCSELs enables remarkable arbitrary control of the laser beam profiles, including self-collimation, Bessel and Vortex lasers, with high efficiency. Such wafer-level integration of metasurface through VCSEL-compatible technology simplifies the assembling process and preserves the high performance of the VCSELs. We envision that our approach can be implemented in various wide-field applications, such as optical fibre communications, laser printing, smartphones, optical sensing, face recognition, directional displays and ultra-compact light detection and ranging (LiDAR).
Cancer is one of the leading causes of death globally, but its burden is not uniform. GLOBOCAN 2020 has newly updated the estimates of cancer burden. This study summarizes the most recent changing ...profiles of cancer burden worldwide and in China and compares the cancer data of China with those of other regions.
We conducted a descriptive secondary analysis of the GLOBOCAN 2020 data. To depict the changing global profile of the leading cancer types in 2020 compared with 2018, we extracted the numbers of cases and deaths in 2018 from GLOBOCAN 2018. We also obtained cancer incidence and mortality from the 2015 National Cancer Registry Report in China when sorting the leading cancer types by new cases and deaths. For the leading cancer types according to sex in China, we summarized the estimated numbers of incidence and mortality, and calculated China's percentage of the global new cases and deaths.
Breast cancer displaced lung cancer to become the most leading diagnosed cancer worldwide in 2020. Lung, liver, stomach, breast, and colon cancers were the top five leading causes of cancer-related death, among which liver cancer changed from the third-highest cancer mortality in 2018 to the second-highest in 2020. China accounted for 24% of newly diagnosed cases and 30% of the cancer-related deaths worldwide in 2020. Among the 185 countries included in the database, China's age-standardized incidence rate (204.8 per 100,000) ranked 65th and the age-standardized mortality rate (129.4 per 100,000) ranked 13th. The two rates were above the global average. Lung cancer remained the most common cancer type and the leading cause of cancer death in China. However, breast cancer became the most frequent cancer type among women if the incidence was stratified by sex. Incidences of colorectal cancer and breast cancer increased rapidly. The leading causes of cancer death varied minimally in ranking from 2015 to 2020 in China. Gastrointestinal cancers, including stomach, colorectal, liver, and esophageal cancers, contributed to a massive burden of cancer for both sexes.
The burden of breast cancer is increasing globally. China is undergoing cancer transition with an increasing burden of lung cancer, gastrointestinal cancer, and breast cancers. The mortality rate of cancer in China is high. Comprehensive strategies are urgently needed to target China's changing profiles of the cancer burden.
The automated steering control technology is crucial for an autonomous vehicle, but due to parametric uncertainties and time varying, the performance of automated steering control can be degraded. ...Therefore, a vehicle automated steering controller based on a model predictive control (MPC) approach is proposed in this article. First, considering tire nonlinear characteristics, the state and control matrices are modified, then the time-varying vehicle speed is considered and a linear parameter varying lateral model is established through utilizing a polytope with finite vertices to describe vehicle longitudinal velocity. Then, the MPC-based vehicle path tracking controller, which is robust against parameter uncertainties, is designed; the proposed controller can be solved via a set of linear matrix inequalities (LMI), which are derived from Lyapunov asymptotic stability and the minimization of the worst case infinite horizon quadratic objective function. The proposed control system is evaluated by both cosimulations of MATLAB/Simulink & CarSim and real-bus tests. Results show the effectiveness of the proposed controller, and it can ensure the control accuracy and strong robustness.
Globally, colorectal cancer (CRC) imposes a substantial burden on healthcare systems and confers considerable medical expenditures. We aimed to evaluate the global and regional burden in ...epidemiological trends and factors associated with the incidence and mortality of CRC.
We used data from the GLOBOCAN database to estimate CRC incidence and mortality worldwide in 2020 and their association with the human development index (HDI). Trends of age-standardized rates of incidence and mortality in 60 countries (2000-2019) were evaluated by Joinpoint regression analysis using data of Global Burden of Disease 2019. The association between exposure to country-level lifestyle, metabolic and socioeconomic factors obtained from the World Health Organization Global Health Observatory and World Bank DataBank data and CRC incidence and mortality was determined by multivariable linear regression.
CRC incidence and mortality varied greatly in the 60 selected countries, and much higher incidence and mortality were observed in countries with higher HDIs, and vice versa. From 2000 to 2019, significant increases of incidence and mortality were observed for 33 countries (average annual percent changes AAPCs, 0.24-3.82) and 18 countries (AAPCs, 0.41-2.22), respectively. A stronger increase in incidence was observed among males (AAPCs, 0.36-4.54) and individuals <50 years (AAPCs, 0.56-3.86). Notably, 15 countries showed significant decreases in both incidence (AAPCs, -0.24 to -2.19) and mortality (AAPCs, -0.84 to -2.74). A significant increase of incidence among individuals <50 years was observed in 30 countries (AAPCs, 0.28-3.62). Countries with higher incidence were more likely to have a higher prevalence of alcohol drinking, higher level of cholesterol level, higher level of unemployment, and a poorer healthcare system.
Some high-HDI countries showed decreasing trends in CRC incidence and mortality, whereas developing countries that previously had low disease burden showed significantly increased incidence and mortality trends, especially in males and populations ≥50 years, which require targeted preventive health programs.
The clinical efficacy of the hospital preparation compound granules of Hedyotis diffusa (CGHD), which is composed of Hedyotis diffusa Willd, Smilax china L., Solanum lyratum Thunb., has accumulated a ...good reputation over the past decades. However, because it is a hospital preparation, few researchers have paid attention to it, resulting in a lack of systematic basic research studies. Thus, it is not clear whether there are safety concerns that restrict its clinical application, and toxicological evaluation of CGHD is needed.
The aim of this study was to evaluate the safety of CGHD by conducting acute toxicity and long-term toxicity experiments, with the objective of providing evidence for its clinical safety and a theoretical foundation for its clinical application.
KM mice were selected for the acute toxicity experiment and were administered water or CGHD-E 3 times within 24 h. The reactions of the animals to CGHD treatment were observed and recorded within 1 h after administration and then once a day for 14 consecutive days. SD rats were selected to conduct the long-term toxicity experiment. The drug-treated groups were administered different doses of CGHD-E, which were equivalent to 10 times, 20 times and 50 times the clinical dose in humans. The rats were administered the drug for 28 consecutive days. After 28 days, the animals were sacrificed, and routine blood tests, blood coagulation function analysis, liver and kidney function tests, and glycolipid metabolism related tests were conducted. The major organs of the rats were collected to calculate organ coefficients and perform hematoxylin-eosin (HE) staining.
In the CGHD-E acute toxicity experiment, the drug-treated groups did not show adverse reactions or poisoning symptoms, and the maximum tolerated dose of CGHD-E in mice was greater than 45.072 g/kg. In the long-term toxicity experiment, drug-treated rats generally exhibited a good condition, but continuous administration decreased on body weight and food intake, especially in male rats. Coagulation function alterations and the impact on the liver during long-term drug administration were also assessed, which should be emphasized in clinical applications. No significant toxic effects were observed according to routine blood tests or test of liver and kidney function, glucose and lipid metabolism, or ion metabolism.
The results of this study showed that CGHD was nontoxic or had low toxicity, providing not only a scientific basis for its clinical application, determining the appropriate clinical dose and monitoring clinical toxicity but also theoretical support for subsequent clinical drug trials.
Increasing evidence indicates that stimulating hippocampal neurogenesis could provide novel avenues for the treatment of depression, and recent studies have shown that in vitro neurogenesis is ...enhanced by hypoxia. The aim of this study was to investigate the potential regulatory capacity of an intermittent hypobaric hypoxia (IH) regimen on hippocampal neurogenesis and its possible antidepressant-like effect. Here, we show that IH promotes the proliferation of endogenous neuroprogenitors leading to more newborn neurons in hippocampus in adult rats. Importantly, IH produces antidepressant-like effects in multiple animal models screening for antidepressant activity, including the forced swimming test, chronic mild stress paradigm, and novelty-suppressed feeding test. Hippocampal x-ray irradiation blocked both the neurogenic and behavioral effects of IH, indicating that IH likely produces antidepressant-like effects via promoting neurogenesis in adult hippocampus. Furthermore, IH stably enhanced the expression of BDNF in hippocampus; both the antidepressant-like effect and the enhancement of cell proliferation induced by IH were totally blocked by pharmacological and biological inhibition of BDNF-TrkB (tyrosine receptor kinase B) signaling, suggesting that the neurogenic and antidepressant-like effects of IH may involve BDNF signaling. These observations might contribute to both a better understanding of physiological responses to IH and to developing IH as a novel therapeutic approach for depression.
•Regulatory T cells are involved in immunosuppressive tumor microenvironment.•Targeting Regulatory T cells represents a promising antitumor immunotherapy.•Immunotherapies by targeting Treg cells by ...using regulators are reviewed.•Include immune checkpoints, co-stimulatory molecules, cytokine receptors and agents.•Points to the future direction of this therapy.•Provides timely and comprehensive information on immunotherapies.
Regulatory T (Treg) cells maintain immune homeostasis by inhibiting abnormal/overactive immune responses to both autogenic and nonautogenic antigens. Treg cells play an important role in immune tolerance, autoimmune diseases, infectious diseases, organ transplantation, and tumor diseases. Treg cells have two functional characteristics: T cell anergy and immunosuppression. Treg cells remain immune unresponsive to high concentrations of interleukin-2 and anti-CD3 monoclonal antibodies. In addition, the activation of Treg cells after TCR-mediated signal stimulation inhibits the activation and proliferation of effector T cells. In the process of tumor development, Treg cells accumulate locally in the tumor and lead to tumor escape by inducing anergy and immunosuppression. It is believed that targeted elimination of Treg cells can activate tumor-specific effector T cells and improve the efficiency of cancer immunotherapy. Therefore, inhibition/clearance of Treg cells is a promising strategy for enhancing antitumor immunity. Here, we review studies of cancer immunotherapies targeting Treg cells.
Acute graft-versus-host disease (aGVHD) remains the major cause of early mortality after haploidentical related donor (HID) hematopoietic stem cell transplantation (HSCT). We aimed to establish a ...comprehensive model which could predict severe aGVHD after HID HSCT.
Consecutive 470 acute leukemia patients receiving HID HSCT according to the protocol registered at https://clinicaltrials.gov (NCT03756675) were enrolled, 70% of them (n = 335) were randomly selected as training cohort and the remains 30% (n = 135) were used as validation cohort.
The equation was as follows: Probability (grade III-IV aGVHD) = Formula: see text, where Y = -0.0288 × (age) + 0.7965 × (gender) + 0.8371 × (CD3 + /CD14 + cells ratio in graft) + 0.5829 × (donor/recipient relation) - 0.0089 × (CD8 + cell counts in graft) - 2.9046. The threshold of probability was 0.057392 which helped separate patients into high- and low-risk groups. The 100-day cumulative incidence of grade III-IV aGVHD in the low- and high-risk groups was 4.1% (95% CI 1.9-6.3%) versus 12.8% (95% CI 7.4-18.2%) (P = 0.001), 3.2% (95% CI 1.2-5.1%) versus 10.6% (95% CI 4.7-16.5%) (P = 0.006), and 6.1% (95% CI 1.3-10.9%) versus 19.4% (95% CI 6.3-32.5%) (P = 0.017), respectively, in total, training, and validation cohort. The rates of grade III-IV skin and gut aGVHD in high-risk group were both significantly higher than those of low-risk group. This model could also predict grade II-IV and grade I-IV aGVHD.
We established a model which could predict the development of severe aGVHD in HID HSCT recipients.
Liver cancer is caused by complex interactions among genetic factors, viral infection, alcohol abuse, and metabolic diseases. We conducted a genome-wide association study and polygenic risk score ...(PRS) model in Taiwan, employing a nonspecific etiology approach, to identify genetic risk factors for hepatocellular carcinoma (HCC). Our analysis of 2836 HCC cases and 134,549 controls revealed 13 novel associated loci such as the FAM66C gene, noncoding genes, liver-fibrosis-related genes, metabolism-related genes, and HCC-related pathway genes. We incorporated the results from the UK Biobank and Japanese database into our study for meta-analysis to validate our findings. We also identified specific subtypes of the major histocompatibility complex that influence both viral infection and HCC progression. Using this data, we developed a PRS to predict HCC risk in the general population, patients with HCC, and HCC-affected families. The PRS demonstrated higher risk scores in families with multiple HCCs and other cancer cases. This study presents a novel approach to HCC risk analysis, identifies seven new genes associated with HCC development, and introduces a reproducible PRS model for risk assessment.
PDF
