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Abstract DNA cleavage by nanomaterials has the potential to be utilized as an innovative tool for gene editing. Numerous nanomaterials exhibiting DNA cleavage properties have been identified and cataloged. Yet, the exploitation of property data through data-driven machine-learning approaches remains unexplored. A database was developed, compiling thirty distinctive characteristics, encompassing physical and chemical properties, as well as experimental conditions of nanomaterials that have demonstrated DNA cleavage capability such as in articles published over the past two decades. The DNA cleavage effect and efficiency of nanomaterials were predicted using machine learning algorithms such as support vector machines, deep neural networks, and random forest, and a classification accuracy of 0.93 for the cleavage effect was achieved. Moreover, the potential of utilizing larger datasets to enhance the predictive capacity of models was discussed. The findings indicate the feasibility of predicting nanomaterial properties based on experimental data. Evaluating the performance and effectiveness of the machine learning models trained using the existing data can furnish valuable insights for future materials research endeavors, especially for the design of DNA cleavage with specific sites.

Abstract Herein, thermally responsive reversible chiral supramolecules are reported, constructed by the chirality transfer from tripeptides to achiral network supramolecular organic frameworks (SOF) based on configurationally stepping confinement, which displayed not only highly selective reversible chirality transfer but also efficient enhanced near‐infrared (NIR) luminescence. Taking advantage of macrocyclic confinement, CB[8] separately encapsulated two kinds of tetracationic bis(phenothiazines) derivatives (G1, G2) at 2:1 stoichiometric to form organic 2D SOFs, efficiently enhancing 12.6 fold NIR luminescence and blueshifted from 705 to 680 nm for G1, and redshifted from 695 to 710 nm for G2, respectively. Uncommonly, the tripeptide coassembled with two kinds of achiral noncovalent frameworks (G1/CB[8] or G2/CB[8]) displayed different opposite circular dichroism signals based on different binding modes and affinity, achieving chirality transfer from tripeptide to organic supramolecular assemblies with further enhanced NIR fluorescence up to 46.2 times and the quantum yield (QY) increased from 0.71% to 10.29% for G2/CB[8], showing reversible chirality transfer and tunable NIR fluorescence under thermal stimulus. Therefore, the current research has achieved controllable chirality transfer from tripeptide to the SOFs and the enhancement of tunable NIR fluorescence, which is successfully applied in thermal responsive chiral logic gates, information encryption, and cell imaging.

Summary: Inflammatory bowel disease (IBD) has high prevalence in Western counties. The high fat content in Western diets is one of the leading causes for this prevalence; however, the underlying mechanisms have not been fully defined. Here, we find that high-fat diet (HFD) induces ferroptosis of intestinal regulatory T (Treg) cells, which might be the key initiating step for the disruption of immunotolerance and the development of colitis. Compared with effector T cells, Treg cells favor lipid metabolism and prefer polyunsaturated fatty acids (PUFAs) for the synthesis of membrane phospholipids. Therefore, consumption of HFD, which has high content of PUFAs such as arachidonic acid, cultivates vulnerable Tregs that are fragile to lipid peroxidation and ferroptosis. Treg-cell-specific deficiency of GPX4, the key enzyme in maintaining cellular redox homeostasis and preventing ferroptosis, dramatically aggravates the pathogenesis of HFD-induced IBD. Taken together, these studies expand our understanding of IBD etiology.

Celiac disease (CD), a gluten‐related disease, is a multi‐system rare disorder mainly involving the gastrointestinal tract. The clinical signs of CD are exceedingly heterogeneous, which increases the difficulty of clinical differential diagnosis. Neurological manifestations are one of the non‐classical CD symptoms. As some patients present only neurological symptoms at early stages, the diagnosis of CD is always delayed. Correct diagnosis and management could decrease patient morbidity and deaths. A 32‐year‐old male was admitted to the hospital due to progressive muscle atrophy of both lower limbs and lumbar stiffness. Based on positive gluten‐sensitive enteropathy autoantibody profiles and gastroscopy foundation, the diagnosis of CD was established. The patient was instructed to gluten‐free diet. The antibody titer of gluten‐sensitive enteropathy autoantibodies decreased, and the patient's symptoms alleviated. We emphasize the importance of CD screening in patients with neurological disorders of unknown aetiology.

The concept of “all cores are created equal” has been popular for several decades due to its simplicity and effectiveness in CPU (Central Processing Unit) design. The more cores the CPU has, the higher performance the host owns and the higher the power consumption. However, power-saving is also one of the key goals for servers in data centers and embedded devices (e.g., mobile phones). The big.LITTLE multicore architecture, which contains high-performance cores (namely big core) and power-saved cores (namely little core), has been developed by ARM (Advanced RISC Machine) and Intel to trade off performance and power efficiency. Facing the new heterogeneous computing architecture, the traditional lock algorithms, which are designed to run on homogeneous computing architecture, cannot work optimally as usual and drop into the performance issue for the difference between big core and little core. In our preliminary experiment, we observed that, in the big.LITTLE multicore architecture, all these lock algorithms exhibit sub-optimal performance. The FIFO-based (First In First Out) locks experience throughput degradation, while the performance of competition-based locks can be divided into two categories. One of them is big-core-friendly, so their tail latency increases significantly; the other is little-core-friendly. Not only does the tail latency increase, but the throughput is also degraded. Motivated by this observation, we propose a Core-Aware Lock for the big.LITTLE multicore architecture named CAL, which keeps each core having an equal opportunity to access the critical section in the program. The core idea of the CAL is to take the slowdown ratio as the matric to reorder lock requests of these big and little cores. By evaluating benchmarks and a real-world application named LevelDB, CAL is confirmed to achieve fairness goals in heterogeneous computing architecture without sacrificing the performance of the big core. Compared to several traditional lock algorithms, the CAL’s fairness has increased by up to 67%; and Its throughput is 26% higher than FIFO-based locks and 53% higher than competition-based locks, respectively. In addition, the tail latency of CAL is always kept at a low level.

Owing to environmental and lifestyle changes in modern society, physical and mental stress is on the rise among the population in attempting to compensate for the changes. Stress, defined as a series of non-specific responses to abnormal internal and external stimuli, has long been recognized to increase susceptibility to various diseases, including neurodegenerative diseases (NDs). Herpes simplex virus type 1 (HSV-1), a neurotropic herpes virus, establishes latent infections in the trigeminal ganglia for the lifetime of the host. Upon reactivation, the latent HSV-1 enters the lytic cycle, which not only causes a substantial production of reactive oxygen species (ROS) in the neurons, but also induces glial cells to produce inflammatory mediators, eventually resulting in neuronal damage and occurrence of NDs. Remarkably, both physical and psychological stress are common stimuli leading to latent HSV-1 reactivation. Acyclovir is a classic antiviral drug for the treatment of HSV-1 infection and recurrence, but acyclovir cannot reverse neuronal damage caused by HSV-1 reactivation. Recent studies have shown that traditional Chinese medicine (TCM) has advantages in the treatment of NDs. In addition, TCM is thought to prevent latent HSV-1 reactivation and NDs, which may involve regulation of the neuro-endocrine-immune network, treatment of emotional disorders, and modulation of oxidative stress. Understanding the mechanism underlying stress-induced reactivation of latent HSV-1 and the potential consequences of NDs is needed. TCM may be a promising alternative therapy for related diseases.

Although NAND (Not And) flash-based Solid-State Drive (SSD) has recently demonstrated a significant performance advantage against hard disk, it still suffers from non-negligible performance under-utilization issues as the access conflict often occurs during servicing IO requests due to the share mechanism (e.g., several chips share one channel bus, several planes share one data register inside the die). Many research works have been devoted to minimizing access conflict by redesigning IO scheduling, cache replacement, and so on. These works have achieved reasonable results; however, the potential data similarity characterization is not utilized fully in prior works to alleviate access conflict. The basic idea is that, as data duplication is common in many workloads where data with the same content from different requests could be distributed to the address with minimized access conflict (i.e., the address does not share the same channel or chip), the logic address is mapped to more than one physical address. Therefore, the data can be read out from candidate pages when the channel or chip of its original address is busy. Motivated by this idea, we propose Data Similarity aware Flash Translation Layer (DS-FTL), which mainly includes a content-aware page allocation scheme and a multi-path read scheme. The DS-FTL enables maximization of the channel-level and chip-level parallelism and avoids the read stall induced by bus-shared mechanisms. We also conducted a series of experiments on SSDsim, with the subsequent results depicting the effectiveness of our scheme. Compared with the state-of-art, our scheme reduces read latency by 35.3% on average in our workloads.

Water resources are important for supporting regional economic development. A scientific and reasonable evaluation of the carrying capacity of water resources is of high significance to regional sustainable development. Zhangjiakou City is China’s first capital water conservation functional area, which plays a role in ensuring the safety of water resources and ecological environment in the capital. Considering Chicheng County, Zhangjiakou City, as a typical area, its water resource carrying capacity in the current year (2018) and the plan year (2025) is evaluated by constructing a water resource carrying capacity evaluation index system for the county, determining the threshold of the bearing capacity evaluation index, and using the single-factor evaluation method and cloud theory method. In addition, the main factors affecting the water resource carrying capacity of Chicheng County are analyzed. The results show that: Based on the single factor evaluation results, the critical state of water resources carrying capacity was evaluated comprehensively, and the factor carrying capacity of total water consumption in the predicted planning level year (38.0603 in normal water year and 41.3403 in dry water year) does not exceed the total water consumption index (51.14). Furthermore, The water resources carrying capacity level of the present level year (.45) and the planned level year (.46) belong to the third level of the evaluation index system. There is further scope for the carrying capacity of water resources in Chicheng County to satisfy its economic and social development. However, it is urgent to solve the problems affecting the water quality elements of rivers, such as heavy river water pollution, low sewage treatment capacity, and weak pollution monitoring and supervision. It is necessary to optimize the industrial economic structure of Chicheng County, accelerate the improvement of water resources management system and mechanism, and ensure the long-term safety of water resources and ecological environment in the capital.

To investigate the failure mode and strength characteristics of rock-like materials containing two non-coplanar closed discontinues, and the influence of crack attitude on the shear failure of rock mass, a series of direct shear tests are carried out on rock-like materials containing two pre-existing cracks of different attitudes, one of them is horizontal crack, and the other is inclined crack. The specimens containing pre-existing cracks of four inclinations (0°, 45°, 135°, and 180°) and three dip angles (30°, 60°, and 90°) are prepared, and the failure form and stress-displacement curve are recorded during the tests. The results show that the attitude of the crack has a significant effect on the failure form and strength characteristics. In positive shear, the shear stress increases slowly and the crack initiation of the crack occurs relatively late, and in negative shear, the shear stress increases rapidly and the crack initiation stage appears earlier. Under the normal stress of 1 MPa, the fracture surface fluctuates along the pre-existing cracks, and the difference in shear strength of each specimen is less than 1.0 MPa. Under the normal stress of 5 MPa, the fracture surface mostly distributes along the horizontal direction, and the difference in shear strength of each specimen is about 2.0 MPa. Under the same level of normal stress, the crack initiation and peak stress vary with the attitude of pre-existing crack, and the variation trend of peak stress is changed when the normal stress increased due to the difference in failure form. It is calculated that the ratio of crack initiation stress to peak stress ranges from 0.61 to 0.80.

Background: In this study, we analyzed intestinal flora in an experimental mouse model of chronic kidney disease (CKD) and investigated whether oral supplementation with probiotic Lactobacillus rhamnosus GG could slow the decline in renal function and inflammatory status of mice with CKD. Methods: We surgically induced chronic kidney disease in C57BL/6J male mice aged 8–9 weeks. We used dual-stage 5/6 nephrectomy for this, while the mock group underwent a mock procedure. The experimental (CKD mice) and mock group were administered a daily dose of 10 × 109 colony forming unit (CFU) of probiotic L. rhamnosus GG or 2 g of maltodextrin as a placebo by oral gavage, respectively, for 5 weeks. At the end of the experiment, the fecal samples of the mice were collected and prepared for intestinal microbial diversity analysis. We examined the serum chemistry and renal histology of the mice. Results: Important serum and blood biomarkers were associated with the development of CKD, including increased serum concentrations of creatine, cystatin C, blood urea nitrogen (BUN), and a protein—interleukin-6 (denoted as IL-6), whereas decreased serum albumin concentration was also observed in the mice with CKD. The intestinal flora of the mice with CKD significantly declined in terms of diversity, richness, and homogeneity. The consumption of L. rhamnosus GG probiotic via oral gavage significantly decreased the serum concentration level present in creatinine and blood urea nitrogen. However, it increased albumin in the group with CKD. After probiotic treatment, serum IL-6 levels dropped considerably, and the kidney histopathology score in mice with CKD who were given L. rhamnosus GG improved. Moreover, supplementation with the probiotic significantly improved floral richness and lineage diversity in the mice with CKD.Conclusions: In this study, we found that probiotics significantly attenuated renal failure development, reduced serum levels of proinflammatory cytokine IL-6, and increased the abundance and lineage diversity of intestinal flora in mice with chronic kidney disease.

Maternal stress has been associated with poor birth outcomes, including preterm birth, infant mortality, and low birth weight. Bone development disorders in the embryo as a result of maternal stress are believed to be mediated through oxidative stress damage. Various species of free radicals, such as alkoxyl radicals, can be formed through endogenous redox response or exogenous stimuli in the womb and transmitted to embryos. Yet, whether these free radicals lead to abnormal fetal bone development is unclear. Here, we demonstrate prenatal bone growth retardation and ferroptosis-related signals of chondrocytes were induced by classic alkoxyl radical generators. We also show that alkoxyl radicals lead to significant accumulation of oxidized phospholipids in chondrocytes, through the iron-mediated Fenton reaction in embryos. We further demonstrate a role for the lipid peroxidation end product, 4-HNE, which forms adducts with the pivotal chondrogenesis transcription factor SOX9, leading to its degradation, therefore dampening chondrogenesis. Our data define a critical role for phospholipid peroxidation in alkoxyl radicals-evoked abnormal chondrogenesis, and pinpoint it being a precise target for treating oxidative stress-related bone development disorders.

Traumatic brain injury (TBI) is a major cause of death and disability in the population worldwide, of which key injury mechanism involving the death of nerve cells. Many recent studies have shown that regulatory necrosis is involved in the pathological process of TBI which includes necroptosis, pyroptosis, ferroptosis, parthanatos, and Cyclophilin D (CypD) mediated necrosis. Therefore, targeting the signaling pathways involved in regulatory necrosis may be an effective strategy to reduce the secondary injury after TBI. Meanwhile, drugs or genes are used as interference factors in various types of regulatory necrosis, so as to explore the potential treatment methods for the secondary injury after TBI. This review summarizes the current progress on regulatory necrosis in TBI.

Tetrandrine citrate (TetC), a novel tetrandrine salt with high water solubility, demonstrates a potent antitumor activity in chronic myeloid leukemia. Studies have indicated an important role of ferroptosis in breast cancer (BC). However, whether TetC inhibits BC progression via ferroptosis has never been explored. In the present study, we showed that TetC had a significant inhibitory effect on the proliferation and migration of MCF7 and MDA-MB-231 cells. Then, we combined TetC with different inhibitors to determine which form of cell death could be driven by TetC. MTT assay showed that ferrostatin (Fer-1) demonstrated the most potent effect on improving TetC-induced cell death in contrast to other inhibitors. TetC was also shown to significantly increase the mRNA level of prostaglandin-endoperoxide synthase 2 (Ptgs2), a ferroptosis marker. Further studies showed that TetC significantly suppressed the expression of glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1) but increased the expression of nuclear receptor coactivator 4 (NCOA4) in MCF7 and MDA-MB-231 cells even in the presence of erastin or Ras-selective lethal 3 (RSL3). Collectively, we showed novel data that ferroptosis was a major form of TetC-induced cell death. Moreover, TetC-induced ferroptotic cell death was achieved via suppressing GPX4 expression and activating NCOA4-mediated ferritinophagy in BC cells.

Based on the analysis of air quality data in Yunnan Province from 2015 to 2020, combined with spatial interpolation analysis and geographic detector factor analysis, the spatial–temporal evolution characteristics of air quality in Yunnan Province have been studied, and the main driving factors, the mechanisms, and the impact of regional COVID-19 control measures affecting air quality have been discussed. The results show that the air quality in Yunnan Province was generally good (superior rate > 98%) from 2015 to 2020, that the Air Quality Index (AQI) value is better in the wet season than in the dry season, and that the concentration of major pollutants shows a decreasing trend. AQI values are spatially high in the east and low in the west. The relative humidity, precipitation, population density, building construction area, and civil vehicles have a greater degree of explanation for the spatial differentiation of AQI, whereas the synergistic influence (maximum value 0.92) of socio-economic factors and meteorological factors is significantly greater than that of a single factor (maximum value 0.80) by the geographic detector model. The control measures for COVID-19 in 2020 reduced the concentration of major pollutants in the atmosphere to a certain extent. Controlling regional air pollution in urban agglomerations in low-latitude plateau areas can improve their air quality by reducing human activities. However, the control of O3 concentration is more complex, and more restrictive factors need to be considered. The results will provide a scientific basis for the prevention and control of air pollution in plateau cities.

To improve the robotic assembly effects in unstructured environments, a reinforcement learning (RL) algorithm is introduced to realize a variable admittance control. In this article, the mechanisms of a peg-in-hole assembly task and admittance model are first analyzed to guide the control strategy and experimental parameters design. Then, the admittance parameter identification process is defined as the Markov decision process (MDP) problem and solved with the RL algorithm. Furthermore, a fuzzy reward system is established to evaluate the action–state value to solve the complex reward establishment problem, where the fuzzy reward includes a process reward and a failure punishment. Finally, four sets of experiments are carried out, including assembly experiments based on the position control, fuzzy control, and RL algorithm. The necessity of compliance control is demonstrated in the first experiment. The advantages of the proposed algorithms are validated by comparing them with different experimental results. Moreover, the generalization ability of the RL algorithm is tested in the last two experiments. The results indicate that the proposed RL algorithm effectively improves the robotic compliance assembly ability.

The Tarim River Basin (TRB) is one of the world’s largest cotton-producing areas, and its agricultural water use accounts for up to 95% of the total water consumption in the basin. Quantifying the future changes in the irrigation area carrying capacity under global warming is therefore essential in TRB. In this study, we analyzed the variation in the irrigation area in TRB over the last few decades, utilized the nonlinear autoregressive with an exogenous input neural network to simulate the future changes in the available water resources, and predicted the future irrigation area carrying capacity based on the water balance equation. The results showed that the present (1970–2020) irrigation area in TRB exhibited an increasing trend from 491 km2 in 1970s to 1382 km2 in 2020, as most of the natural vegetation was transformed into cropland. In the future (2022–2050), the available water resource will show an upward tendency while the irrigation area carrying capacity mainly ranges from 12×102–21×102 km2 and 17×102–30×102 km2 under scenarios SSP (shared socioeconomic pathway) 245 and SSP585, respectively. The simulated results will provide useful information for the allocation of water resources and the regional sustainable development of TRB.