Regional noise source location based on the time delays between station pairs from ambient noise interferometry.

Identifying the location of a potential noise source assists in understanding the characteristics of the seismic or volcanic activity and provides valuable information for hazard assessment. Unlike the conventional waveform-based techniques that rebuild the source energy into the possible source region, we apply a simplified method to determine the absolute location of the noise source based on the station-pair time-delays from ambient noise interferometry. Synthetic tests demonstrate the robustness of the method and the locating precision is mainly influenced by the signal-to-noise ratio of the synthetic waveforms, and the higher frequency bandwidth source signals are more likely to result in accurate detection of the source. An application at the Central Tien Shan indicates that our method is capable of locating the known virtual source from the empirical Green's functions. Furthermore, assuming a surface wave velocity, the depth of the source can be generally recovered from ambient noise interferometry in a simplified 3-D homogeneous model. The new method sheds light on applications of ambient noise interferometry for locating potential sources, making it suitable for detecting time-dependent behavior.

Wireless flow-powered miniature robot capable of traversing tubular structures.

Wireless millimeter-scale robots capable of navigating through fluid-flowing tubular structures hold substantial potential for inspection, maintenance, or repair use in nuclear, industrial, and medical applications. However, prevalent reliance on external powering constrains these robots' operational range and applicable environments. Alternatives with onboard powering must trade off size, functionality, and operation duration. Here, we propose a wireless millimeter-scale wheeled robot capable of using environmental flows to power and actuate its long-distance locomotion through complex pipelines. The flow-powering module can convert flow energy into mechanical energy, achieving an impeller speed of up to 9595 revolutions per minute, accompanied by an output power density of 11.7 watts per cubic meter and an efficiency of 33.7%. A miniature gearbox module can further transmit the converted mechanical energy into the robot's locomotion system, allowing the robot to move against water flow at an average rate of up to 1.05 meters per second. The robot's motion status (moving against/with flow or pausing) can be switched using an external magnetic field or an onboard mechanical regulator, contingent on different proposed control designs. In addition, we designed kirigami-based soft wheels for adaptive locomotion. The robot can move against flows of various substances within pipes featuring complex geometries and diverse materials. Solely powered by flow, the robot can transport cylindrical payloads with a diameter of up to 55% of the pipe's diameter and carry devices such as an endoscopic camera for pipeline inspection, a wireless temperature sensor for environmental temperature monitoring, and a leak-stopper shell for infrastructure maintenance.

Genetic separation of Brca1 functions reveal mutation-dependent Polθ vulnerabilities.

Homologous recombination (HR)-deficiency induces a dependency on DNA polymerase theta (Polθ/Polq)-mediated end joining, and Polθ inhibitors (Polθi) are in development for cancer therapy. BRCA1 and BRCA2 deficient cells are thought to be synthetic lethal with Polθ, but whether distinct HR gene mutations give rise to equivalent Polθ-dependence, and the events that drive lethality, are unclear. In this study, we utilized mouse models with separate Brca1 functional defects to mechanistically define Brca1-Polθ synthetic lethality. Surprisingly, homozygous Brca1 mutant, Polq-/- cells were viable, but grew slowly and had chromosomal instability. Brca1 mutant cells proficient in DNA end resection were significantly more dependent on Polθ for viability; here, treatment with Polθi elevated RPA foci, which persisted through mitosis. In an isogenic system, BRCA1 null cells were defective, but PALB2 and BRCA2 mutant cells exhibited active resection, and consequently stronger sensitivity to Polθi. Thus, DNA end resection is a critical determinant of Polθi sensitivity in HR-deficient cells, and should be considered when selecting patients for clinical studies.

Isochromosome 7p, i(7)(p10): A rare AML, myelodysplasia-related entity.

We describe genomic findings in an AML case with isochromosome 7p, i(7)(p10), in which SNP array analysis uncovered an additional 7.07-Mb 20q deletion not detected by karyotyping. Several AML cases with i(7)(p10) as an isolated cytogenetic finding have been previously reported. Based on consequent loss of 7q, we propose that AML with i(7)(p10) represents a distinct entity belonging in the WHO group -7/7q-, which represents one of the genetic abnormalities defining AML, myelodysplasia-related. Additionally, the focal del(20q) identified here adds support for a specific common region of deletion in 20q in myeloid malignancies, implicating a small number of candidate genes.

360° Digital Travel to Improve Emotional State and Well-Being During the COVID-19 Pandemic: The Role of Presence and Sense of Place.

The continuation of the COVID-19 pandemic has caused a decline in people's subjective well-being and emotional states. Digital travel based on 360° videos provides an alternate way for people to improve their mental health at home during this specific period. Yet, how to construct effective digital travel content that improves emotions remains an issue. This investigation assessed the impact of people's perceived presence and sense of place (SOP) on emotional improvement during a 360° digital travel experience. A total of 156 undergraduate students volunteered to participate, and anxiety, emotion levels, and life satisfaction were measured before and after the digital travel experience; presence and SOP ratings were also collected after the experience. A Latent Change Score model was then developed, and the results indicated that the greater presence and SOP individuals experienced during their digital travel, the better their digital travel experience and emotional improvement. Furthermore, the current data highlight that SOP has a greater impact on emotional improvement than presence. This result provides a novel understanding that how SOP is generated may be more critical to digital travel than presence. This new understanding should help improve relevant applications in the field of digital travel, such as the possibility of providing meaningful narrative context in a virtual environment to induce SOP more effectively, and improve the digital travel experience. Overall, the findings of this study expand our understanding of the digital travel experience and lay the groundwork for future research on SOP and digital travel.

A Thermopile-Based Gas Flow Sensor with High Sensitivity for Noninvasive Respiration Monitoring.

In this work, a N/P polySi thermopile-based gas flow device is presented, in which a microheater distributed in a comb-shaped structure is embedded around hot junctions of thermocouples. The unique design of the thermopile and the microheater effectively enhances performance of the gas flow sensor leading to a high sensitivity (around 6.6 µV/(sccm)/mW, without amplification), fast response (around 35 ms), high accuracy (around 0.95%), and mood long-term stability. In addition, the sensor has the advantages of easy production and compact size. With such characteristics, the sensor is further used in real-time respiration monitoring. It allows detailed and convenient collection of respiration rhythm waveform with sufficient resolution. Information such as respiration periods and amplitudes can be further extracted to predict and alert of potential apnea and other abnormal status. It is expected that such a novel sensor could provide a new approach for respiration monitoring related noninvasive healthcare systems in the future.

New ε-N-thioglutaryl-lysine derivatives as SIRT5 inhibitors: Chemical synthesis, kinetic and crystallographic studies.

SIRT5 has been implicated in various physiological processes and human diseases, including cancer. Development of new highly potent, selective SIRT5 inhibitors is still needed to investigate disease-related mechanisms and therapeutic potentials. We here report new ε-N-thioglutaryllysine derivatives, which were designed according to SIRT5-catalysed deacylation reactions. These ε-N-thioglutaryllysine derivatives displayed potent SIRT5 inhibition, of which the potential photo-crosslinking derivative 8 manifested most potent inhibition with an IC50 value of 120 nM to SIRT5, and low inhibition to SIRT1-3 and SIRT6. The enzyme kinetic assays revealed that the ε-N-thioglutaryllysine derivatives inhibit SIRT5 by lysine-substrate competitive manner. Co-crystallographic analyses demonstrated that 8 binds to occupy the lysine-substate binding site by making hydrogen-bonding and electrostatic interactions with SIRT5-specific residues, and is likely positioned to react with NAD+ and form stable thio-intermediates. Compound 8 was observed to have low photo-crosslinking probability to SIRT5, possibly due to inappropriate position of the diazirine group as observed in SIRT5:8 crystal structure. This study provides useful information for developing drug-like inhibitors and cross-linking chemical probes for SIRT5-related studies.

Visualizing Cathepsin K-Cre Expression at the Single-Cell Level with GFP Reporters.

The Cre/lox system is a fundamental tool for functional genomic studies, and a number of Cre lines have been generated to target genes of interest spatially and temporally in defined cells or tissues; this approach has greatly expanded our knowledge of gene functions. However, the limitations of this system have recently been recognized, and we must address the challenge of so-called nonspecific/off-target effects when a Cre line is utilized to investigate a gene of interest. For example, cathepsin K (Ctsk) has been used as a specific osteoclast marker, and Cre driven by its promoter is widely utilized for osteoclast investigations. However, Ctsk-Cre expression has recently been identified in other cell types, such as osteocytes, periosteal stem cells, and tenocytes. To better understand Ctsk-Cre expression and ensure appropriate use of this Cre line, we performed a comprehensive analysis of Ctsk-Cre expression at the single-cell level in major organs and tissues using two green fluorescent protein (GFP) reporters (ROSA nT-nG and ROSA tdT) and a tissue clearing technique in young and aging mice. The expression profile was further verified by immunofluorescence staining and droplet digital RT-PCR. The results demonstrate that Ctsk-Cre is expressed not only in osteoclasts but also at various levels in osteoblast lineage cells and other major organs/tissues, particularly in the brain, kidney, pancreas, and blood vessels. Furthermore, Ctsk-Cre expression increases markedly in the bone marrow, skeletal muscle, and intervertebral discs in aging mice. These data will be valuable for accurately interpreting data obtained from in vivo studies using Ctsk-Cre mice to avoid potentially misleading conclusions. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

A modularity design approach to behavioral research with immersive virtual reality: A SkyrimVR-based behavioral experimental framework.

Virtual reality (VR) has been shown to be a potential research tool, yet the gap between traditional and VR behavioral experiment systems poses a challenge for many behavioral researchers. To address the challenge posed, the present study first adopted a modularity design strategy and proposed a five-module architectural framework for a VR behavioral experiment system that aimed to reduce complexity and costs of development. Applying the five-module architectural framework, the present study developed the SkyrimVR-based behavioral experimental framework (SkyBXF) module, a basic experimental framework module that adopted and integrated the classic human behavior experiment structure (i.e., session-block-trial model) with the modifiable VR massive gaming franchise The Elder Scrolls V: Skyrim VR. A modified version of previous behavioral research to investigate the effects of masked peripheral vision on visually-induced motion sickness in an immersive virtual environment was conducted as a proof of concept to showcase the feasibility of the proposed five-module architectural framework and the SkyBXF module developed. Behavioral data acquired through the case study were consistent with those from previous behavioral research. This indicates the viability of the proposed five-module architectural framework and the SkyBXF module developed, and provides proof that future behavioral researchers with minimal programming proficiency, 3D environment development expertise, time, personnel, and resources may reuse ready-to-go resources and behavioral experiment templates offered by SkyBXF to swiftly establish realistic virtual worlds that can be further customized for experimental need on the go.

Study on the Influencing Factors and Willingness to Pay of Consumers Purchasing Ecological Agricultural Products.

With the steady rise of China's agricultural production and management level, the market of ecological agricultural products has developed rapidly, and consumers are increasingly concerned about ecological agricultural products. Consumers' cognition and purchase intention are the keys to determine their future development. This research is aimed at ensuring that consumers have access to high-quality ecological agricultural products, thereby promoting the supply and production of ecological agricultural products, minimizing agricultural carbon emissions, and providing information on sustainable food pricing. Based on the research status at home and abroad, this study combines the questionnaire survey method to study the influencing factors and willingness to pay of consumers purchasing ecological agricultural products. A total of 601 online questionnaires from consumers in Harbin, a city in northeastern China, were collected, and statistical factor analysis, principal component analysis, and regression analysis were used to study the influencing factors of consumers' purchase of ecological agricultural products from both positive and negative aspects, and in-depth analysis of the reasons why consumers refuse to pay, get the most real willingness to pay and related influencing factors, and quantify the influence of various variables on consumers' purchasing behavior was done. On this basis, a logit model of survival analysis is constructed to study the premium payment level of consumers for ecological agricultural products, and the payment premium is 24.95%. The research results show that married, who have purchased ecological agricultural products, the higher the understanding of ecological agricultural products, the consumers who buy ecological agricultural products in farmers' markets, Meituan and community group purchases, and the households with higher monthly consumption of agricultural products have a significant positive correlation with consumers' purchase of ecological agricultural products. The higher the education level, the older the age, and the larger the family size were significantly negatively correlated with consumers' purchase of ecological agricultural products.

Ferroptosis and Its Multifaceted Role in Cancer: Mechanisms and Therapeutic Approach.

Ferroptosis, a new type of non-apoptotic cell death modality, is different from other modes of cell death and has been primarily found in tumor cells. Previous studies have reported that ferroptosis can be triggered by specific modulators (e.g., drugs, nutrients, and iron chelators), leading to increased intracellular lipid reactive oxygen species (ROS) accumulation and iron overload. Recent reports have shown that ferroptosis at the cellular and organism levels can prevent an inflammatory storm and cancer development. Emerging evidence suggests potential mechanisms (e.g., system Xc-, glutathione peroxidase 4 (GPX4), lipid peroxidation, glutathione (GSH), and iron chelators) are involved in ferroptosis, which may mediate biological processes such as oxidative stress and iron overload to treat cancer. To date, there are at least three pathways that mediate ferroptosis in cancer cells: system Xc-/GSH/GPX4, FSP1/CoQ10/NAD(P)H, and ATG5/ATG7/NCOA4. Here, we summarize recent advances in the occurrence and development of ferroptosis in the context of cancer, the associations between ferroptosis and various modulators, and the potential mechanisms and therapeutic strategies targeting ferroptosis for the treatment of cancer.

Soft-robotic ciliated epidermis for reconfigurable coordinated fluid manipulation.

The fluid manipulation capabilities of current artificial cilia are severely handicapped by the inability to reconfigure near-surface flow on various static or dynamically deforming three-dimensional (3D) substrates. To overcome this challenge, we propose an electrically driven soft-robotic ciliated epidermis with multiple independently controlled polypyrrole bending actuators. The beating kinematics and the coordination of multiple actuators can be dynamically reconfigured to control the strength and direction of fluid transportation. We achieve fluid transportation along and perpendicular to the beating directions of the actuator arrays, and toward or away from the substrate. The ciliated epidermises are bendable and stretchable and can be deployed on various static or dynamically deforming 3D surfaces. They enable previously difficult to obtain fluid manipulation functionalities, such as transporting fluid in tubular structures or enhancing fluid transportation near dynamically bending and expanding surfaces.

Usability and Effects of a Combined Physical and Cognitive Intervention Based on Active Video Games for Preschool Children.

Executive functions (EFs) are essential for early childhood development, and effective programs to improve EFs in preschool education are becoming increasingly crucial. There is rising evidence that combined physical-cognitive intervention training utilizing active video games (exergames) could be a viable strategy to improve EFs. However, there is a shortage of empirical evidence on the application of this approach in preschool education. The effectiveness of exergame intervention training in preschools must be evaluated. This study conducted a randomized controlled trial to assess the effects of exergames intervention training on preschool children's EFs. A total of 48 participants aged 4-5 years were enrolled; 24 were randomly allocated to receive exergames physical activity training, and the remaining 24 received conventional physical activity training. After a four-week intervention, the children who received the exergames intervention training exhibited considerably greater gains in all three EFs tasks than children who received the conventional physical activity program. Follow-up interviews revealed that the children accepted the exergames well. The results demonstrate the viability of incorporating exergames into preschool education to improve children's EFs, supporting prior findings and offering more empirical evidence from early childhood research.

Bioinspired Stretchable Fiber-Based Sensor toward Intelligent Human-Machine Interactions.

Wearable integrated sensing devices with flexible electronic elements exhibit enormous potential in human-machine interfaces (HMI), but they have limitations such as complex structures, poor waterproofness, and electromagnetic interference. Herein, inspired by the profile of Lindernia nummularifolia (LN), a bionic stretchable optical strain (BSOS) sensor composed of an LN-shaped optical fiber incorporated with a stretchable substrate is developed for intelligent HMI. Such a sensor enables large strain and bending angle measurements with temperature self-compensation by the intensity difference of two fiber Bragg gratings' (FBGs') center wavelength. Such configurations enable an excellent tensile strain range of up to 80%, moreover, leading to ultrasensitivity, durability (≥20,000 cycles), and waterproofness. The sensor is also capable of measuring different human activities and achieving HMI control, including immersive virtual reality, robot remote interactive control, and personal hands-free communication. Combined with the machine learning technique, gesture classification can be achieved using muscle activity signals captured from the BSOS sensor, which can be employed to obtain the motion intention of the prosthetic. These merits effectively indicate its potential as a solution for medical care HMI and show promise in smart medical and rehabilitation medicine.

Creating three-dimensional magnetic functional microdevices via molding-integrated direct laser writing.

Magnetically driven wireless miniature devices have become promising recently in healthcare, information technology, and many other fields. However, they lack advanced fabrication methods to go down to micrometer length scales with heterogeneous functional materials, complex three-dimensional (3D) geometries, and 3D programmable magnetization profiles. To fill this gap, we propose a molding-integrated direct laser writing-based microfabrication approach in this study and showcase its advanced enabling capabilities with various proof-of-concept functional microdevice prototypes. Unique motions and functionalities, such as metachronal coordinated motion, fluid mixing, function reprogramming, geometrical reconfiguring, multiple degrees-of-freedom rotation, and wireless stiffness tuning are exemplary demonstrations of the versatility of this fabrication method. Such facile fabrication strategy can be applied toward building next-generation smart microsystems in healthcare, robotics, metamaterials, microfluidics, and programmable matter.

Effects of Dietary Protein Level on the Microbial Composition and Metabolomic Profile in Postweaning Piglets.

Since the human and porcine digestive systems have similar anatomical structures and physiological functions, pigs are a useful animal model for studying human digestive diseases. By investigating intestinal metabolites in piglets after weaning, this study attempted to identify the inherent connection between dietary protein levels and changes in the intestinal microbiota of piglets. Casein was employed as the only source of protein for the piglets in this study to avoid the influence of other protein sources. 14 weaning at 28-day-old piglets (6.9 ± 0.19 kg) formed into two dietary groups: 17% casein fed group (LP) and 30% casein fed group (HP). Piglets were allowed to free food and water during the 2-week experiment. Throughout the trial, the piglets' diarrhea index (1: no diarrhea and 3: watery diarrhea) and food intake were noted during the experiment. We discovered piglets fed a high-protein diet developed diarrhea throughout the duration of the research, whereas piglets fed a normal protein diet did not. In addition, the HP group had lower feed intake and body weight than the control group (P < 0.05). The HP diet influenced the content of short-chain and branched-chain fatty acids in the colon, including acetate and isovaleric acid. The ileal microbiota's 16S rRNA gene was sequenced, and it was discovered that the relative abundance of gastrointestinal bacteria differed between the HP and control groups. Dietary protein levels influenced bile acid biosynthesis, alpha-linolenic acid metabolism, phospholipid biosynthesis, arachidonic acid metabolism, fatty acid biosynthesis, retinol metabolism, arginine and proline metabolism, pyrimidine metabolism, tryptophan metabolism, and glycine and serine metabolism, according to gas chromatography-mass spectrometry analysis. Furthermore, a correlation analysis of the pooled information revealed a possible link between intestinal metabolites and specific bacteria species. These findings demonstrate that weaned piglets' microbiota composition and metabolites are modified by a high-protein diet and thus inducing severe postweaning diarrhea and inhibiting growth performance. However, the potential molecular mechanism of this regulation in the growth of piglets remains unclear.

Soft-bodied adaptive multimodal locomotion strategies in fluid-filled confined spaces.

Soft-bodied locomotion in fluid-filled confined spaces is critical for future wireless medical robots operating inside vessels, tubes, channels, and cavities of the human body, which are filled with stagnant or flowing biological fluids. However, the active soft-bodied locomotion is challenging to achieve when the robot size is comparable with the cross-sectional dimension of these confined spaces. Here, we propose various control and performance enhancement strategies to let the sheet-shaped soft millirobots achieve multimodal locomotion, including rolling, undulatory crawling, undulatory swimming, and helical surface crawling depending on different fluid-filled confined environments. With these locomotion modes, the sheet-shaped soft robot can navigate through straight or bent gaps with varying sizes, tortuous channels, and tubes with a flowing fluid inside. Such soft robot design along with its control and performance enhancement strategies are promising to be applied in future wireless soft medical robots inside various fluid-filled tight regions of the human body.

Voxelated three-dimensional miniature magnetic soft machines via multimaterial heterogeneous assembly.

Small-scale soft-bodied machines that respond to externally applied magnetic field have attracted wide research interest because of their unique capabilities and promising potential in a variety of fields, especially for biomedical applications. When the size of such machines approach the sub-millimeter scale, their designs and functionalities are severely constrained by the available fabrication methods, which only work with limited materials, geometries, and magnetization profiles. To free such constraints, here, we propose a bottom-up assembly-based 3D microfabrication approach to create complex 3D miniature wireless magnetic soft machines at the milli- and sub-millimeter scale with arbitrary multimaterial compositions, arbitrary 3D geometries, and arbitrary programmable 3D magnetization profiles at high spatial resolution. This approach helps us concurrently realize diverse characteristics on the machines, including programmable shape morphing, negative Poisson's ratio, complex stiffness distribution, directional joint bending, and remagnetization for shape reconfiguration. It enlarges the design space and enables biomedical device-related functionalities that are previously difficult to achieve, including peristaltic pumping of biological fluids and transport of solid objects, active targeted cargo transport and delivery, liquid biopsy, and reversible surface anchoring in tortuous tubular environments withstanding fluid flows, all at the sub-millimeter scale. This work improves the achievable complexity of 3D magnetic soft machines and boosts their future capabilities for applications in robotics and biomedical engineering.

D-Galactose Induces Chronic Oxidative Stress and Alters Gut Microbiota in Weaned Piglets.

Oxidative stress commonly occurs in pig production, which can severely damage the intestinal function of weaned piglets. This study was conducted to investigate the effects of D-galactose with different levels used to induce chronic oxidative stress on growth performance, intestinal morphology and gut microbiota in weaned piglets. The results showed that addition of 10 and 20 g/kg BW D-galactose reduced average daily gain and average daily feed intake from the first to the third week. 10 g/kg BW D-galactose increased the concentration of serum MDA at the second and third week. 10 g/kg BW D-galactose significantly influenced the jejunal and ileal expressions of GPx1, CAT1, and MnSOD. The results of 16S rRNA sequencing showed that compared with the control, 10 and 20 g/kg BW D-galactose significantly decreased the relative abundance of Tenericutes, Erysipelotrichia, Erysipelotrichales, and Erysipelotrichaceae, while increased the relative abundance of Negativicutes, Selenomonnadales, and Veillonellaceae. The results indicated that treatment with 10 g/kg BW/day D-galactose for 3 weeks could induce chronic oxidative stress, reduce the growth performance and alter gut microbiota in weaned piglets.

Immortalization of human primary prostate epithelial cells via CRISPR inactivation of the CDKN2A locus and expression of telomerase.

BACKGROUND: Immortalization of primary prostate epithelial cells (PrEC) with just hTERT expression is particularly inefficient in the absence of DNA tumor viral proteins or p16INK4A knockdown. MATERIALS AND METHODS: Here, we describe the establishment of immortalized normal prostate epithelial cell line models using CRISPR technology to inactivate the CDKN2A locus concomitantly with ectopic expression of an hTERT transgene. RESULTS: Using this approach, we have obtained immortal cell clones that exhibit fundamental characteristics of normal cells, including diploid genomes, near normal karyotypes, normal p53 and pRB cell responses, the ability to form non-invasive spheroids, and a non-transformed phenotype. Based on marker expression, these clones are of basal cell origin. CONCLUSIONS: Use of this approach resulted in the immortalization of independent clones of PrEC that retained normal characteristics, were stable, and non-transformed. Thus, this approach could be used for the immortalization of normal primary prostate cells. This technique could also be useful for establishing cell lines from prostate tumor tissues of different tumor grades and/or from patients of diverse ethnicities to generate cell line models that facilitate the study of the molecular basis of disease disparity.