•There are estimated 1.93 million new CRC cases diagnosed, and 0.94 million CRC caused deaths in 2020 worldwide.•The global new CRC cases is predicted to reach 3.2 million in 2040.•China and the ...United States have the highest estimated number of new CRC cases in the next 20 years.•The number of new CRC cases is increased from 0.56 million (2020) to 0.91 million (2040) in China.•The number of new CRC cases is increased from 0.16 million (2020) to 0.21 million (2040) in the United States.
As the third most common malignancy and the second most deadly cancer, colorectal cancer (CRC) induces estimated 1.9 million incidence cases and 0.9 million deaths worldwide in 2020. The incidence of CRC is higher in highly developed countries, and it is increasing in middle- and low-income countries due to westernization. Moreover, a rising incidence of early-onset CRC is also emerging. The large number of CRC cases poses a growing global public health challenge. Raising awareness of CRC is important to promote healthy lifestyle choices, novel strategies for CRC management, and implementation of global screening programs, which are critical to reducing CRC morbidity and mortality in the future. CRC is a heterogeneous disease, and its subtype affiliation influences prognosis and therapeutic response. An accurate CRC subtype classification system is of great significance for basic research and clinical outcome. Here, we present the global epidemiology of CRC in 2020 and projections for 2040, review the major CRC subtypes to better understand CRC molecular basis, and summarize current risk factors, prevention, and screening strategies for CRC.
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In this study, we conducted a literature review of relevant research and then statistically analyzed global greenhouse gas (GHG) emissions from natural systems, including forest fires, oceans, ...wetlands, permafrost, mud volcanoes, volcanoes, and earthquakes. Drawing on the Global Carbon Project (GCP) report, we also summarized the global anthropogenic GHG emissions. We then compared the global annual GHG emissions from natural systems with those generated by human activity. The results indicate that the global annual GHG emissions range approximately between 54.33 and 75.50 Gt CO2-eq, of which natural emissions account for 18.13–39.30 Gt CO2-eq, with the most likely value being approximately 29.07 Gt CO2-eq. According to the GCP report, the global anthropogenic emissions have increased from 22 Gt CO2-eq in 1990 to 36.2 Gt CO2-eq in 2016. The amounts of natural and anthropogenic GHGs emissions are roughly of the same order of magnitude. Anthropogenic emissions account for approximately 55.46% of the total global GHGs emissions (2016 value), i.e., the ratio of natural to anthropogenic emissions is approximately 0.8. In addition, the annual amount of GHGs absorbed by Earth systems (ocean and terrestrial ecosystems) ranges between approximately 14.4 Gt CO2-eq and 26.5 Gt CO2-eq, with natural system GHG emissions and sinks also having roughly the same order of magnitude. This finding indicates that the GHG emissions generated by human activity exert extra pressure on what is otherwise a self-balancing Earth system.
The globally increasing annual incidence of chronic obstructive pulmonary disease (COPD), a common chronic disease, poses a serious risk to public health. Although the exact mechanism underlying the ...pathogenesis of COPD remains unclear, a large number of studies have shown that its pathophysiology and disease course are closely related to oxidative stress, inflammation, apoptosis, autophagy, and aging. The key players involved in COPD include the sirtuin family of NAD-dependent deacetylases that comprise seven members (SIRT1-7) in mammals. Sirtuins play an important role in metabolic diseases, cell cycle control, proliferation, apoptosis, and senescence. Owing to differences in subcellular localization, sirtuins exhibit anisotropy. In this narrative review, we discuss the roles and molecular pathways of each member of the sirtuin family involved in COPD to provide novel insights into the prevention and treatment of COPD and how sirtuins may serve as adjuvants for COPD treatment.
The incidence of obesity and colorectal cancer (CRC) has risen rapidly in recent decades. More than 650 million obese and 2 billion overweight individuals are currently living in the world. CRC is ...the third most common cancer. Obesity is regarded as one of the key environmental risk factors for the pathogenesis of CRC. In the present review, we mainly focus on the epidemiology of obesity and CRC in the world, the United States, and China. We also summarize the molecular mechanisms linking obesity to CRC in different aspects, including nutriology, adipokines and hormones, inflammation, gut microbiota, and bile acids. The unmet medical needs for obesity-related CRC are still remarkable. Understanding the molecular basis of these associations will help develop novel therapeutic targets and approaches for the treatment of obesity-related CRC.
The human nervous system senses the physical world in an analogue but efficient way. As a crucial ability of the human brain, sound localization is a representative analogue computing task and often ...employed in virtual auditory systems. Different from well-demonstrated classification applications, all output neurons in localization tasks contribute to the predicted direction, introducing much higher challenges for hardware demonstration with memristor arrays. In this work, with the proposed multi-threshold-update scheme, we experimentally demonstrate the in-situ learning ability of the sound localization function in a 1K analogue memristor array. The experimental and evaluation results reveal that the scheme improves the training accuracy by ∼45.7% compared to the existing method and reduces the energy consumption by ∼184× relative to the previous work. This work represents a significant advance towards memristor-based auditory localization system with low energy consumption and high performance.
Phenothiazinone is a promising yet underutilized fluorophore, possibly due to the lack of a general accessibility. This study reports a robust and scalable TEMPO‐mediated electrochemical method to ...access a variety of phenothiazinones from 2‐aminothiophenols and quinones. The electrosynthesis proceeds in a simple cell architecture under mild condition, and notably carbon–halogen bond in quinones remains compared to conventional methods, enabling orthogonal downstream functionalization. Mechanistic studies corroborate that TEMPO exerts a protective effect in avoiding product decomposition at the cathode. In particular, benzophenothiazinones show intriguing luminescence in both solid and solution state, and thus their photophysical properties are scrutinized in detail. Further bio‐imaging of the lipid droplets in living cells highlights the considerable promise of benzophenothiazinones as fluorescent dye in the biomedical fields.
Electrochemical synthesis of phenothiazinone via oxidative cyclocondensation of quinone and 2‐aminothiophenol under mild condition is presented, along with its bio‐application as fluorophore for lipid droplets imaging in living cells.
The room‐temperature sodium‐sulfur (RT Na‐S) batteries have been seriously hindered in their practical application due to the sluggish redox kinetics and incomplete conversion of polysulfides. In ...this study, a structure‐determined Keggin‐type heteropolyvanadotungstate of H5PW10V2O40·30H2O (PW10V2) is engineered and reveal its catalytic mechanism in RT Na‐S system. With the assistance of precise V sites and highly reversible multi‐electron redox properties, PW10V2 as a bidirectional molecular catalyst expedites the complete conversions between polysulfides and the insoluble sodium sulfide, while undergoing the reversible transformation between its reduced and oxidized states. Furthermore, PW10V2 with multicenter active sites can capture polysulfides efficiently. Consequently, the cell with the constructed PW10V2‐based modified separator achieves the perdurable cyclability up to 4000 loops even at 10 C toward an exceptionally low capacity decay rate of 0.012% per cycle, far surpassing those of current state‐of‐the‐art RT Na‐S batteries that employ the functional materials based on separator. This work first demonstrates the underlying electrochemical reaction processes of polyoxometalate‐based functional materials, which guides solving the challenging issues related to sodium polysulfides in RT Na‐S batteries.
The structure‐determined Keggin‐type heteropolyvanadotungstate of H5PW10V2O40·30H2O (PW10V2) can function as a bidirectional molecular catalyst to unlock the complete conversions of S8 reduction and Na2S oxidation via two‐step 1, 2‐electron transfer behavior. Moreover, the V active center is more conducive to enhancing the adsorption of PW10V2 for NaPSs, which prominently restrains the shuttle effect of polysulfides.
In this article, we review the existing analog resistive switching memory (RSM) devices and their hardware technologies for in-memory learning, as well as their challenges and prospects. Since the ...characteristics of the devices are different for in-memory learning and digital memory applications, it is important to have an in-depth understanding across different layers from devices and circuits to architectures and algorithms. First, based on a top-down view from architecture to devices for analog computing, we define the main figures of merit (FoMs) and perform a comprehensive analysis of analog RSM hardware including the basic device characteristics, hardware algorithms, and the corresponding mapping methods for device arrays, as well as the architecture and circuit design considerations for neural networks. Second, we classify the FoMs of analog RSM devices into two levels. Level 1 FoMs are essential for achieving the functionality of a system (e.g., linearity, symmetry, dynamic range, level numbers, fluctuation, variability, and yield). Level 2 FoMs are those that make a functional system more efficient and reliable (e.g., area, operational voltage, energy consumption, speed, endurance, retention, and compatibility with back-end-of-line processing). By constructing a device-to-application simulation framework, we perform an in-depth analysis of how these FoMs influence in-memory learning and give a target list of the device requirements. Lastly, we evaluate the main FoMs of most existing devices with analog characteristics and review optimization methods from programming schemes to materials and device structures. The key challenges and prospects from the device to system level for analog RSM devices are discussed.
Background Internal tandem duplication (ITD) mutations in the juxtamembrane domain–coding sequence of the Fms-like tyrosine kinase 3 (FLT3) gene have been identified in 30% of acute myeloid leukemia ...(AML) patients and are associated with a poor prognosis. The kinase inhibitor sorafenib induces growth arrest and apoptosis at much lower concentrations in AML cell lines that harbor FLT3-ITD mutations than in AML cell lines with wild-type FLT3. Methods The antileukemic activity of sorafenib was investigated in isogenic murine Ba/F3 AML cell lines that expressed mutant (ITD, D835G, and D835Y) or wild-type human FLT3, in primary human AML cells, and in a mouse leukemia xenograft model. Effects of sorafenib on apoptosis and signaling in AML cell lines were investigated by flow cytometry and immunoblot analysis, respectively, and the in vivo effects were determined by monitoring the survival of leukemia xenograft–bearing mice treated with sorafenib (groups of 15 mice). In a phase 1 clinical trial, 16 patients with refractory or relapsed AML were treated with sorafenib on different dose schedules. We determined their FLT3 mutation status by a polymerase chain reaction assay and analyzed clinical responses by standard criteria. All statistical tests were two-sided. Results Sorafenib was 1000- to 3000-fold more effective in inducing growth arrest and apoptosis in Ba/F3 cells with FLT3-ITD or D835G mutations than in Ba/F3 cells with FLT3-D835Y mutant or wild-type FLT3 and inhibited the phosphorylation of tyrosine residues in ITD mutant but not wild-type FLT3 protein. In a mouse model, sorafenib decreased the leukemia burden and prolonged survival (median survival in the sorafenib-treated group vs the vehicle-treated group = 36.5 vs 16 days, difference = 20.5 days, 95% confidence interval = 20.3 to 21.3 days; P = .0018). Sorafenib reduced the percentage of leukemia blasts in the peripheral blood and the bone marrow of AML patients with FLT3-ITD (median percentages before and after sorafenib: 81% vs 7.5% P = .016 and 75.5% vs 34% P = .05, respectively) but not in patients without this mutation. Conclusion Sorafenib may have therapeutic efficacy in AML patients whose cells harbor FLT3-ITD mutations.
Scope
High‐fat‐diet (HFD) is an important factor in obesity. Extracellular matrix (ECM) regulates white adipose tissue (WAT), but its mechanism is unknown.
Methods and Results
This study uses three ...models—HFD‐fed mice, human with obesity, and 3T3‐L1 adipocytes with oleic acid (OA)/macromolecular crowders (MMC) treatment. Glucose and lipids metabolic disorders, increased collagen I/IV and laminin α2/4 (LAMA2/4), and upregulated integrins (ITGA1/ITGA7) – focal adhesion kinase (FAK) – c‐Jun N‐terminal kinase (JNK)/extracellular regulated protein kinase 1/2 (ERK1/2) signals in obese WAT from mice and human are observed. The upregulation of ECM – integrin – FAK signals is stronger in subcutaneous WAT than that in visceral WAT of mice, but these results are reversed in human. In vitro, oleic acid (OA) promotes lipid accumulation and upregulates collagen IV, LAMA4, and p‐JNK. MMC is used to induce ECM deposition in adipocytes. MMC promotes adipocyte differentiation and integrins – FAK – JNK/ERK1/2 signals. When FAK phosphorylation is inhibited, downstream p‐JNK is decreased. Inhibition of FAK phosphorylation reduces adipocyte differentiation, but MMC partially reverses this effect.
Conclusion
HFD‐induced ECM deposition, whose signals are transmitted into adipocytes through upregulating ITGA1/ITGA7, activates the phosphorylation of intracellular FAK – JNK/ERK1/2 signals, and promotes adipogenesis in WAT. This mechanism provides novel therapeutic targets to treat obesity.
High‐fat‐diet‐induced extracellular matrix (ECM, e.g., collagen I/IV, and LAMA2/4) deposition upregulate integrin (ITGA1/ITGA7) expression in adipocytes. Integrins activate the downstream phosphorylation of intracellular FAK – JNK/ERK1/2 signals to promote white adipose tissue (WAT) adipogenesis when obesity occurs. These signals are stronger in subcutaneous WAT than that in visceral WAT of mice, but the results are reversed in human WAT.
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