LILRB4 on multiple myeloma cells promotes bone lesion by p-SHP2/NF-κB/RELT signal pathway.

BACKGROUND: Leukocyte Ig-like receptor B family 4 (LILRB4) as an immune checkpoint on myeloid cells is a potential target for tumor therapy. Extensive osteolytic bone lesion is the most characteristic feature of multiple myeloma. It is unclear whether ectopic LILRB4 on multiple myeloma regulates bone lesion. METHODS: The conditioned medium (CM) from LILRB4-WT and -KO cells was used to analyze the effects of LILRB4 on osteoclasts and osteoblasts. Xenograft, syngeneic and patient derived xenograft models were constructed, and micro-CT, H&E staining were used to observe the bone lesion. RNA-seq, cytokine array, qPCR, the activity of luciferase, Co-IP and western blotting were used to clarify the mechanism by which LILRB4 mediated bone damage in multiple myeloma. RESULTS: We comprehensively analyzed the expression of LILRB4 in various tumor tissue arrays, and found that LILRB4 was highly expressed in multiple myeloma samples. The patient's imaging data showed that the higher the expression level of LILRB4, the more serious the bone lesion in patients with multiple myeloma. The conditioned medium from LILRB4-WT not -KO cells could significantly promote the differentiation and maturation of osteoclasts. Xenograft, syngeneic and patient derived xenograft models furtherly confirmed that LILRB4 could mediate bone lesion of multiple myeloma. Next, cytokine array was performed to identify the differentially expressed cytokines, and RELT was identified and regulated by LILRB4. The overexpression or exogenous RELT could regenerate the bone damage in LILRB4-KO cells in vitro and in vivo. The deletion of LILRB4, anti-LILRB4 alone or in combination with bortezomib could significantly delay the progression of bone lesion of multiple myeloma. CONCLUSIONS: Our findings indicated that LILRB4 promoted the bone lesion by promoting the differentiation and mature of osteoclasts through secreting RELT, and blocking LILRB4 singling pathway could inhibit the bone lesion.

Protozoan-Derived Cytokine-Transgenic Macrophages Reverse Hepatic Fibrosis.

Macrophage therapy for liver fibrosis is on the cusp of meaningful clinical utility. Due to the heterogeneities of macrophages, it is urgent to develop safer macrophages with a more stable and defined phenotype for the treatment of liver fibrosis. Herein, a new macrophage-based immunotherapy using macrophages stably expressing a pivotal cytokine from Toxoplasma gondii, a parasite that infects ≈ 2 billion people is developed. It is found that Toxoplasma gondii macrophage migration inhibitory factor-transgenic macrophage (Mφtgmif) shows stable fibrinolysis and strong chemotactic capacity. Mφtgmif effectively ameliorates liver fibrosis and deactivates aHSCs by recruiting Ly6Chi macrophages via paracrine CCL2 and polarizing them into the restorative Ly6Clo macrophage through the secretion of CX3CL1. Remarkably, Mφtgmif exhibits even higher chemotactic potential, lower grade of inflammation, and better therapeutic effects than LPS/IFN-γ-treated macrophages, making macrophage-based immune therapy more efficient and safer. Mechanistically, TgMIF promotes CCL2 expression by activating the ERK/HMGB1/NF-κB pathway, and this event is associated with recruiting endogenous macrophages into the fibrosis liver. The findings do not merely identify viable immunotherapy for liver fibrosis but also suggest a therapeutic strategy based on the evolutionarily designed immunomodulator to treat human diseases by modifying the immune microenvironment.

Human milk-derived MANF, as an immuno-nutritional factor, maintains the intestinal epithelial barrier and protects against necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a leading cause of death in preterm infants. Compared to formula milk, breastfeeding protects against NEC. However, the composition of breast milk is quite complicated, and many immunological compositions remain unknown. In this study, we aimed to investigate the concentration of a secreted protein, Mesencephalic astrocyte-derived neurotrophic factor (MANF), in breastmilk and evaluate its immune-regulatory function in protecting the intestinal epithelial barrier. Our data indicated that MANF was secreted in human milk but could not be detected in infant formulas. More importantly, the amount of MANF in colostrum was higher than that in mature milk. We also clarified that MANF was mainly expressed in intestinal macrophages and was capable of inducing apoptosis and decreasing the inflammation of pro-inflammatory macrophages in both NEC intestinal tissues and BMDMs. Mechanismly, MANF protein significantly inhibited the apoptosis of intestinal epithelial cells and protected epithelial tight junctions through downregulation of the NF-κB pathway in pro-inflammatory macrophages. These results reveal the crucial function of human milk-derived MANF in intestinal macrophages, which contributes to downregulating the intestinal inflammatory response and protecting the homeostasis of intestinal epithelial cells. Our study not only demonstrates a potential mechanism underlying breastfeeding protective effects in NEC but also, more importantly, enables clinical translation, facilitating new strategies for the development of nutritional interventions in the prevention of NEC.

Targeting the Immunoglobulin IGSF9 Enhances Antitumor T-cell Activity and Sensitivity to Anti-PD-1 Immunotherapy.

Immune checkpoints modulate the immune response and represent important immunotherapy targets for cancer treatment. However, as many tumors are resistant to current immune checkpoint inhibitors, the discovery of novel immune checkpoints could facilitate the development of additional immunotherapeutic strategies to improve patient responses. Here, we identified increased expression of the adhesion molecule immunoglobulin superfamily member 9 (IGSF9) in tumor cells and tumor-infiltrating immune cells across multiple cancer types. IGSF9 overexpression or knockout in tumor cells did not alter cell proliferation in vitro or tumor growth in immunocompromised mice. Alternatively, IGSF9 deficient tumor cells lost the ability to suppress T-cell proliferation and exhibited reduced growth in immunocompetent mice. Similarly, growth of tumor cells was reduced in IGSF9 knockout syngeneic and humanized mice, accompanied by increased tumor-infiltrating T cells. Mechanistically, the extracellular domain (ECD) of IGSF9 bound to T cells and inhibited their proliferation and activation, and the tumor-promoting effect of IGSF9 ECD was reversed by CD3+ T-cell depletion. Anti-IGSF9 antibody treatment inhibited tumor growth and enhanced the antitumor efficacy of anti-programmed cell death protein 1 immunotherapy. Single-cell RNA sequencing revealed tumor microenvironment remodeling from tumor promoting to tumor suppressive following anti-IGSF9 treatment. Together, these results indicate that IGSF9 promotes tumor immune evasion and is a candidate immune checkpoint target. SIGNIFICANCE: IGSF9 is an immune checkpoint regulator that suppresses T-cell activation in cancer and can be targeted to stimulate antitumor immunity and inhibit tumor growth.

Emotional Recognition Training Enhances Attention to Emotional Stimuli Among Male Juvenile Delinquents.

Objective: Juvenile delinquents have deficits in emotional recognition that might play a critical role in the development of aggression. The present study aimed to investigate the effect of emotional recognition training and its consequences on emotional attention and aggression. Methods: Seventy-three male juvenile delinquents were randomly assigned to two groups. One group was the modification group, which received eight days of training on an emotional recognition task. The purpose of the training was to modify interpretative biases in emotion recognition to encourage the perception of happiness over anger in ambiguous expressions. The other group was the waitlist group, which did not perform a task and continued with their usual programme. Before and after the training, participants completed the aggression questionnaire (AQ) and two behavioural tasks, including the emotional recognition task and a visual search task with happy and angry faces as targets. Results: The modification group recognized more faces as happy after emotional recognition training than the waitlist group. Furthermore, the hostility in the modification group decreased significantly. Importantly, emotional recognition training further affected attention to emotional faces as participants responded faster in searching for happy and angry faces after training. Conclusion: Emotional recognition training could modify juvenile delinquents' emotional recognition, enhance their visual attention to emotional faces and reduce hostility.

Parental Burnout and Prosocial Behavior among Chinese Adolescents: The Role of Empathy.

Parental burnout refers to exhaustion caused by the parenting role. This devastating negative emotion can have repercussions for adolescent social development. Nevertheless, much remains unclear about the association between parental burnout and adolescent prosocial behavior and the potential mechanisms underlying this relationship. Based on theoretical and empirical evidence, the current study examined the relationship between parental burnout and adolescent prosocial behavior by using a sequential mediation model that included both parental empathy and adolescent empathy as potential mediators. A total of 488 parent-adolescent dyads (for adolescents: 45.7% men, 54.3% women, Mage = 15.28 ± 1.67 years; for parents: 36.5% fathers, 63.5% mothers, Mage = 41.30 ± 3.79 years) completed questionnaires regarding demographics, social desirability, parental burnout, parental empathy, adolescent empathy, and adolescent prosocial behavior. After controlling for demographic covariates and social desirability, the results showed that parental burnout had a negative effect on adolescent-reported prosocial behavior through parental cognitive empathy and adolescent other-oriented empathy (adolescent cognitive empathy and empathic concern) sequentially. These findings contribute to our understanding of the role of parental burnout as a family environmental factor detrimental to the positive functioning of adolescents through parental reactions to their children's emotions and children's own social competence.

Understanding the Emotion Coping Strategies During Public Emergencies - From the Perspective of Psychological Distance.

Research has investigated behavioral coping strategies for the negative emotions that public emergencies elicit. Accordingly, our current research explored how people coped with negative emotions in response to the coronavirus disease (COVID-19) outbreak, from a cognitive perspective. Building on the theory of psychological distance and self-construal, we proposed that people who experienced fear, sadness and anxiety responded with independent-self construal, focusing on information that related to themselves and the novel virus (independent information). On the other hand, people who experienced fear, sadness and anger responded with interdependent-self construal, focusing on information that pertained to "us", the virus and nature (interdependent information). We collected data from 1,142 participants at both the initial peak of the outbreak and when its spread had subsided. Based on this longitudinal data, we examined the effectiveness of these strategies, and our findings suggested that independent information was effective in decreasing fear and anxiety, while interdependent information effectively mitigated sadness. The findings could help researchers, practitioners, governments, and organizations to implement appropriate information strategies to regulate individuals' negative emotions during and after the COVID-19 pandemic.

Measuring pollutant emissions of cattle breeding and its spatial-temporal variation in China.

The rapid development of animal husbandry has resulted in serious pollution issues in the livestock and poultry breeding industry, increasing the cost of environmental management. This issue is particularly prominent in China due to its rapid economic development, significant domestic consumption, and aggressive carbon neutrality targets. This study analyses pollution emissions and spatial-temporal variation in China's cattle breeding industry. Using an emission coefficient method and panel data of 31 Chinese provinces/municipalities between 2002 and 2017, we measure the total volume of pollutant emissions from China's cattle breeding industry and five major pollutants: chemical oxygen demand, total nitrogen, total phosphorus, copper, and zinc. We also analyse the dynamic variation of the spatial distribution. The results show that both the total emissions volume and emissions of the five major pollutants have decreased to different extents, among which chemical oxygen demand has decreased the fastest. Spatial divergence is strengthened as the heavy pollution areas have moved from the southeast to the northwest of the country. This study contributes to current research by its focus on the cattle breading industry and by our improvements to the pollutant emission measurement method.

"PP-type" self-assembling peptides with superior rheological properties.

The ionic-complementary self-assembling peptides discovered by Zhang Shuguang have solution-to-gel (sol-gel) transition capacity and one such peptide RADA16 has been commercialized into hemostatic agents. However, their sol-gel transition ability was not obvious because the peptide aqueous solution with a concentration greater than 1% w/v appeared to be thick and viscous. The current report describes PP-type self-assembling peptides. In addition to the ionic-complementary sequence, they have prolines at both ends of the sequence. This feature has led to better solubility, lower viscosity of the peptide solution, and simplified synthesis and purification processes while maintaining the great gelling performance of the ionic-complementary peptides. The PP-type peptides self-assembled into a well-organized nanofiber scaffold as shown by TEM. Among the PP-type peptides, the PRVDP9 sequence peptide was tested as a hemostatic agent and a mucosal elevating agent. The results were comparable to the classic RADA16. The PP-type self-assembling peptides have superior sol-gel transition ability. Therefore, it is predicted that they will be more suitable to be transported through catheters or endoscopes and have higher commercialization potential as compared with the classic self-assembling peptide sequences.

Hesperetin ameliorates lipopolysaccharide-induced acute lung injury in mice through regulating the TLR4-MyD88-NF-κB signaling pathway.

Hesperetin, a major bioflavonoid in sweet oranges and lemons, exerts an anti-inflammatory effect in pulmonary diseases; however, its effect on lipopolysaccharide (LPS)-induced acute lung injury is unclear. This study investigated the effect of hesperetin on LPS-induced lung inflammatory response. Mice were intratracheally instilled with 5 mg/kg body weight LPS, and then were given hesperetin orally (10, 20, and 30 mg/kg body weight) 1 h later. Hesperetin dramatically suppressed the levels of interleukin-6 and tumor necrosis factor-α, as well as the number of inflammatory cells in bronchoalveolar lavage fluid. Besides, it reduced lung injury, wet weight/dry weight ratio, and myeloperoxidase and lactate dehydrogenase activities, and enhanced superoxide dismutase activity. In addition, hesperetin significantly downregulated the Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) protein expression and suppressed nuclear factor-kappa B (NF-κB) activation in lung tissue. Together, these results indicated that the anti-inflammatory effect of hesperetin is associated with the TLR4-MyD88-NF-κB pathway, and that hesperetin shows therapeutic potential for LPS-induced acute lung injury.

Indoor Motion Detection Using Wi-Fi Channel State Information in Flat Floor Environments Versus in Staircase Environments.

Recently, Wi-Fi channel state information (CSI) motion detection systems have been widely researched for applications in human health care and security in flat floor environments. However, these systems disregard the indoor context, which is often complex and consists of unique features, such as staircases. Motion detection on a staircase is also meaningful and important for various applications, such as fall detection and intruder detection. In this paper, we present the difference in CSI motion detection in flat floor and staircase environments through analysing the radio propagation model and experiments in real settings. For comparison in the two environments, an indoor CSI motion detection system is proposed with several novel methods including correlation-based fusion, moving variance segmentation (MVS), Doppler spread spectrum to improve the system performance, and a correlation check to reduce the implementation cost. Compared with existing systems, our system is validated to have a better performance in both flat floor and staircase environments, and further utilized to verify the superior CSI motion detection performance in staircase environments versus flat floor environments.

An Adaptive S-Method to Analyze Micro-Doppler Signals for Human Activity Classification.

In this paper, we propose the multiwindow Adaptive S-method (AS-method) distribution approach used in the time-frequency analysis for radar signals. Based on the results of orthogonal Hermite functions that have good time-frequency resolution, we vary the length of window to suppress the oscillating component caused by cross-terms. This method can bring a better compromise in the auto-terms concentration and cross-terms suppressing, which contributes to the multi-component signal separation. Finally, the effective micro signal is extracted by threshold segmentation and envelope extraction. To verify the proposed method, six states of motion are separated by a classifier of a support vector machine (SVM) trained to the extracted features. The trained SVM can detect a human subject with an accuracy of 95.4% for two cases without interference.

A Robust and Device-Free System for the Recognition and Classification of Elderly Activities.

Human activity recognition, tracking and classification is an essential trend in assisted living systems that can help support elderly people with their daily activities. Traditional activity recognition approaches depend on vision-based or sensor-based techniques. Nowadays, a novel promising technique has obtained more attention, namely device-free human activity recognition that neither requires the target object to wear or carry a device nor install cameras in a perceived area. The device-free technique for activity recognition uses only the signals of common wireless local area network (WLAN) devices available everywhere. In this paper, we present a novel elderly activities recognition system by leveraging the fluctuation of the wireless signals caused by human motion. We present an efficient method to select the correct data from the Channel State Information (CSI) streams that were neglected in previous approaches. We apply a Principle Component Analysis method that exposes the useful information from raw CSI. Thereafter, Forest Decision (FD) is adopted to classify the proposed activities and has gained a high accuracy rate. Extensive experiments have been conducted in an indoor environment to test the feasibility of the proposed system with a total of five volunteer users. The evaluation shows that the proposed system is applicable and robust to electromagnetic noise.

3D Tracking via Shoe Sensing.

Most location-based services are based on a global positioning system (GPS), which only works well in outdoor environments. Compared to outdoor environments, indoor localization has created more buzz in recent years as people spent most of their time indoors working at offices and shopping at malls, etc. Existing solutions mainly rely on inertial sensors (i.e., accelerometer and gyroscope) embedded in mobile devices, which are usually not accurate enough to be useful due to the mobile devices' random movements while people are walking. In this paper, we propose the use of shoe sensing (i.e., sensors attached to shoes) to achieve 3D indoor positioning. Specifically, a short-time energy-based approach is used to extract the gait pattern. Moreover, in order to improve the accuracy of vertical distance estimation while the person is climbing upstairs, a state classification is designed to distinguish the walking status including plane motion (i.e., normal walking and jogging horizontally), walking upstairs, and walking downstairs. Furthermore, we also provide a mechanism to reduce the vertical distance accumulation error. Experimental results show that we can achieve nearly 100% accuracy when extracting gait patterns from walking/jogging with a low-cost shoe sensor, and can also achieve 3D indoor real-time positioning with high accuracy.

Effects and Molecular Mechanism of GST-Irisin on Lipolysis and Autocrine Function in 3T3-L1 Adipocytes.

Irisin, which was recently identified as a myokine and an adipokine, transforms white adipose tissue to brown adipose tissue and has increasingly caught the attention of the medical and scientific community. However, the signaling pathway of irisin and the molecular mechanisms responsible for the lipolysis effect remain unclear. In this study, we established an efficient system for the expression and purification of GST-irisin in Escherichia coli. The biological activity of GST-irisin was verified using the cell counting kit-8 assay and by detecting the mRNA expression of uncoupling protein 1. Our data showed that GST-irisin regulates mRNA levels of lipolysis-related genes such as adipose triglyceride lipase and hormone-sensitive lipase and proteins such as the fatty acid-binding protein 4, leading to increased secretion of glycerol and decreased lipid accumulation in 3T3-L1 adipocytes. In addition, exogenous GST-irisin can increase its autocrine function in vitro by regulating the expression of fibronectin type III domain-containing protein 5. GST-irisin could regulate glucose uptake in 3T3-L1 adipocytes. Hence, we believe that recombinant GST-irisin could promote lipolysis and its secretion in vitro and can potentially prevent obesity and related metabolic diseases.

Effect of the ultrasound-Fenton oxidation process with the addition of a chelating agent on the removal of petroleum-based contaminants from soil.

The effects of ultrasonic irradiation, the chelating agent modified Fenton reaction, and a combination of ultrasound and the Fenton method in removing petroleum contaminants from a soil were studied. The results showed that the contaminant removal rate of the Fenton treatment combined with an oxalic acid chelating agent was 55.6% higher than that without a chelating agent. The average removal rate of the contaminants using the ultrasound-Fenton treatment was 59.0% higher than that without ultrasonic treatment. A combination of ultrasound and an Fe(2+)/Fe(3+)-oxalate complex-modified Fenton reagent resulted in significantly higher removal rates of n-alkanes (C(n)H(2n+2), n < 28), isoprenoid hydrocarbons, aromatic hydrocarbons, and saturated polycyclic terpenes compared with the ultrasound treatment alone or the Fenton method. The Fenton reaction and the ultrasound-Fenton treatment can unselectively remove multiple components of residual hydrocarbons and a number of benzene rings in polycyclic aromatic hydrocarbons. The chemistry of the heterocyclic compounds and the position and number of substituents can affect the degradation process.

Tracking and recognition of multiple human targets moving in a wireless pyroelectric infrared sensor network.

With characteristics of low-cost and easy deployment, the distributed wireless pyroelectric infrared sensor network has attracted extensive interest, which aims to make it an alternate infrared video sensor in thermal biometric applications for tracking and identifying human targets. In these applications, effectively processing signals collected from sensors and extracting the features of different human targets has become crucial. This paper proposes the application of empirical mode decomposition and the Hilbert-Huang transform to extract features of moving human targets both in the time domain and the frequency domain. Moreover, the support vector machine is selected as the classifier. The experimental results demonstrate that by using this method the identification rates of multiple moving human targets are around 90%.

Analysis of Photosynthetic Characteristics and UV-B Absorbing Compounds in Mung Bean Using UV-B and Red LED Radiation.

Mung bean has been reported to have antioxidant, antidiabetic, anti-inflammatory, and antitumor activities. Various factors have important effects on the types and contents of plant chemical components. In order to study quality of mung bean from different light sources, mung bean seedlings were exposed to red light-emitting diodes (LEDs) and ultraviolet-B (UV-B). Changes in the growth parameters, photosynthetic characteristics, the concentrations of chlorophyll a and chlorophyll b and the content of UV-B absorbing compounds were measured. The results showed that photosynthetic characteristics and chlorophyll a and chlorophyll b concentrations were enhanced by red LEDs. The concentrations of UV-B absorbing compounds were enhanced by UV-B on the 20th day, while photosynthetic characteristics, plant length, and the concentrations of chlorophyll a and chlorophyll b were reduced by UV-B on the 40th day; at the same time the values of the stem diameter, plant fresh weight, dry weight, and the concentrations of UV-B absorbing compounds were enhanced. It is suggested that red LEDs promote the elongation of plant root growth and photosynthetic characteristics, while UV-B promotes horizontal growth of stems and the synthesis of UV-B absorbing compounds.

The optical effect of a semiconductor laser on protecting wheat from UV-B radiation damage.

Lasers have been widely used in the field of biology along with the development of laser technology, but the mechanism of the bio-effect of lasers is not explicit. The objective of this paper was to test the optical effect of a laser on protecting wheat from UV-B damage. A patent instrument was employed to emit semiconductor laser (wavelength 650 nm) and incoherent red light, which was transformed from the semiconductor laser. The wavelength, power and lightfleck diameter of the incoherent red light are the same as those of the semiconductor laser. The semiconductor laser (wavelength 650 nm, power density 3.97 mW mm(-2)) and incoherent red light (wavelength 650 nm, power density 3.97 mW mm(-2)) directly irradiated the embryo of wheat seeds for 3 min respectively, and when the seedlings were 12-day-old they were irradiated by UV-B radiation (10.08 kJ m(-2)) for 12 h in the dark. Changes in the concentration of malondialdehyde (MDA), hydrogen peroxide (H(2)O(2)), glutathione (GSH), ascorbate (AsA), carotenoids (CAR), the production rate of superoxide radical (O(2)(-)), the activities of peroxidase (POD), catalase (CAT), superoxide dismutase (SOD) and the growth parameters of seedlings (plant height, leaf area and fresh weight) were measured to test the optical effect of the laser. The results showed that the incoherent red light treatment could not enhance the activities of SOD, POD and CAT and the concentration of AsA and CAR. When the plant cells were irradiated by UV-B, the incoherent red light treatment could not eliminate active oxygen and prevent lipid peroxidation in wheat. The results also clearly demonstrate that the plant DNA was damaged by UV-B radiation and semiconductor laser irradiance had the capability to protect plants from UV-B-induced DNA damage, while the incoherent red light could not. This is the first investigation reporting the optical effect of a semiconductor laser on protecting wheat from UV-B radiation damage.

[Combined effects of enhanced UV-B radiation and doubled CO2 on tomato growth and its fruit quality].

The study on the effects of 8.40 kJ x m(-2) UV-B radiation, 700 micromol x mol(-1) CO2 concentration, and their combination on tomato (Lycopersicon esculeutum ) growth and its fruit quality showed that under enhanced UV-B radiation, the plant height, fresh weight, dry weight, photosynthesis rate, water use efficiency, and contents of total chlorophyll, chlorophyll a, chlorophyll b, soluble protein, ascorbate acid (Vitamin C) and lycopene were decreased, which resulted in the deterioration of tomato fruit quality. Doubled CO2 concentration alone accelerated tomato growth, and accordingly, ameliorated its fruit quality. Under the combined effects of enhanced UV-B radiation and doubled CO2 concentration, tomato growth and its fruit quality were not significantly different from the control. It was suggested that the positive effects of doubled CO2 could lighten and counteract the negative effects of UV-B radiation under combined treatment of enhanced UV-B radiation and doubled CO2 concentration.