Aggregation-induced emission luminogens (AIEgens) possess the unique property of enhanced fluorescence and photostability in aggregated states, making them exceptional materials for the convergence of imaging and phototherapy. With their inherent advantages, AIEgens are propelling the field of nanomedicine into a vibrant frontier in the phototheranostics of a spectrum of diseases, particularly in the realm of cancer immunotherapy. AIEgens-based therapeutics enhance the cancer immune response through a variety of approaches, including real-time image-guided precise therapy, induction of programmed cell death, metabolic reprogramming, and modulation of the tumor microenvironment. Additionally, they contribute to the synergistic effect of immune checkpoint inhibition, a pivotal aspect of modern cancer immunotherapy strategies. This review offers a comprehensive overview of the integration of AIEgens in nanomedicine and their role in immune adaptation, highlighting the advantages, basic action mechanisms, and recent advancement of AIEgens as promising therapeutic platform for cancer immunotherapy.

In this paper, we report an ultrastable lithium niobate (LiNbO3) electro-optic modulation phase interrogation technique for Fabry-Perot acoustic sensors. Leveraging the optical characteristics of three paths of birefringent crystals to engender three low -coherence interference signals derived from a solitary light source, wherein one path is composed of two LiNbO3 crystals with different lengths cascaded in series, then engendering periodic electro-optic modulation and concurrent real-time compensation of the other two orthogonal interference signals. This procedure affords the generation of two normalized quadrature signals, which are subsequently subjected to precise phase demodulation. A series of experiments have been carried out to verify the feasibility of the proposed scheme. The proposed scheme can eliminate the influences of irrelevant factors in real-time, the system has excellent linear acoustic pressure response. Specifically, when the input optical power of the system is attenuated by 60 %, or when the initial cavity length of the sensor drifts -2.544 mu m or 2.862 mu m, the system can still be correctly demodulated, and the maximum relative the demodulation errors are 2.046 % and 1.476 %, respectively. With the advantages of strong robustness, large dynamic range and low cost, this scheme has great potential in practical engineering applications.

Operando monitoring gas pressure within the lithium-ion batteries (LIBs) accurately during thermal runaway is essential to comprehending their reaction mechanisms and providing a reliable early warning scheme. Nevertheless, the majority of existing monitoring suffer from hysteresis, susceptibility to external interference, and high cross-sensitivity, resulting in the inability to monitor thermal runaway safely, in situ, and accurately during such extremely hazardous operations. To address this, we develop a method for measuring gas pressure inside the LIBs during thermal runaway based on Fabry-Perot (F-P) interference. The compact sensor monitors gas pressure accurately with a low temperature crosstalk, which is created by welding a chip fabricated with the MicroElectro-Mechanical System (MEMS) technology to the optical fiber end face via carbon dioxide laser. Through experimental demonstrate, we have realized the safe and reliable monitoring for the process of thermal runaway in two kinds of 18650 LIBs and divided it into five stages. Furthermore, an accurate three-level early warning scheme for thermal runaways dominated by gas pressure is proposed by incorporating the internal reaction mechanisms and exterior state characteristics behaviors of LIB. These findings establish an essential basis for improving battery safety and provide a reliable method for LIBs thermal runaway monitoring and early warning.

Mitochondrial dynamics are critical in cellular energy production, metabolism, apoptosis, and immune responses. Pathogenic bacteria have evolved sophisticated mechanisms to manipulate host cells' mitochondrial functions, facilitating their proliferation and dissemination. Salmonella enterica serovar Typhimurium (S. Tm), an intracellular foodborne pathogen, causes diarrhea and exploits host macrophages for survival and replication. However, S. Tm-associated mitochondrial dynamics during macrophage infection remain poorly understood. In this study, we showed that within macrophages, S. Tm remodeled mitochondrial fragmentation to facilitate intracellular proliferation mediated by Salmonella invasion protein A (SipA), a type III secretion system effector encoded by Salmonella pathogenicity island 1. SipA directly targeted mitochondria via its N-terminal mitochondrial targeting sequence, preventing excessive fragmentation and the associated increase in mitochondrial reactive oxygen species, loss of mitochondrial membrane potential, and release of mitochondrial DNA and cytochrome c into the cytosol. Macrophage replication assays and animal experiments showed that mitochondria and SipA interact to facilitate intracellular replication and pathogenicity of S. Tm. Furthermore, we showed that SipA delayed mitochondrial fragmentation by indirectly inhibiting the recruitment of cytosolic dynamin-related protein 1, which mediates mitochondrial fragmentation. This study revealed a novel mechanism through which S. Tm manipulates host mitochondrial dynamics, providing insights into the molecular interplay that facilitates S. Tm adaptation within host macrophages.

Adherent-invasive Escherichia coli (AIEC) strain LF82, isolated from patients with Crohn's disease, invades gut epithelial cells, and replicates in macrophages contributing to chronic inflammation. In this study, we found that RstAB contributing to the colonization of LF82 in a mouse model of chronic colitis by promoting bacterial replication in macrophages. By comparing the transcriptomes of rstAB mutant- and wild-type when infected macrophages, 83 significant differentially expressed genes in LF82 were identified. And we identified two possible RstA target genes (csgD and asr) among the differentially expressed genes. The electrophoretic mobility shift assay and quantitative real-time PCR confirmed that RstA binds to the promoters of csgD and asr and activates their expression. csgD deletion attenuated LF82 intracellular biofilm formation, and asr deletion reduced acid tolerance compared with the wild-type. Acidic pH was shown by quantitative real-time PCR to be the signal sensed by RstAB to activate the expression of csgD and asr. We uncovered a signal transduction pathway whereby LF82, in response to the acidic environment within macrophages, activates transcription of the csgD to promote biofilm formation, and activates transcription of the asr to promote acid tolerance, promoting its replication within macrophages and colonization of the intestine. This finding deepens our understanding of the LF82 replication regulation mechanism in macrophages and offers new perspectives for further studies on AIEC virulence mechanisms.

Efficient adhesion in natural dynamic water could greatly facilitate human aquatic activities. However, the loss of adhesive molecules, the barrier of interfacial water and the difficulty of strong solidification in dynamic water environment hinder the adhesion in natural water in practice. Herein, inspired by the “3C” adhesive mode of marine sessile organisms, we propose a universal applicable concept of water-responsive entanglements (WARE) via a combination of the entanglements and responsiveness of polymers for developing dynamic water-applicable adhesives. We demonstrated that WARE-type adhesives underwent a 3C-mimetic adhesive process, including entangled constraint-mediated initial loss suppression, sufficient dehydration-facilitated underwater contact and water responsiveness-promoted underwater crosslinking, thus completing the adhesive process and achieving strong adhesion in dynamic water. Intriguingly, due to the facile synthesis methodology and unique adhesive mode, the WARE-type adhesives also exhibit traits desirable for practical applications, such as mass producibility, long-term storage, on-demand detachment, and recyclability. Taking common human aquatic activities as examples, we further show the effectiveness of the WARE-type adhesives through their strong adhesive performance in simplifying the underwater exploration process, repairing a broken boat and sealing a leaky underwater pipeline in emergency.

Developing low-frequency acoustic senor with high sensitivity is crucial for diverse applications, ranging from seismic monitoring, military operations, to pipeline surveillance. Here, we have proposed a high-sensitivity graphene oxide (GO)-based Fabry-Perot low-frequency sensor, in which a 170 nm thick, large-area and uniformly GO film was prepared by a vacuum filtration method. To enhance the accuracy and stability of the sensor, a low-coherence interference system based on birefringent crystal blocks was designed utilizing a three-step phase-shifting arctangent algorithm. Our sensor exhibited a sensitivity of -93.48 dB re 1 rad/mu Pa at 6-60 Hz with a fluctuation of 0.6 dB. The minimum detectable pressure of the sensor was measured at 0.37 mu Pa/Hz(1/2) @20 Hz with a signal to noise ratio of 135.41 dB. Overall, this sensor offers simplicity in preparation, high sensitivity, low detectable sound pressure, making it a significant asset for low-frequency acoustic applications.

While oral probiotics show promise in treating inflammatory bowel disease, the primary challenge lies in sustaining their activity and retention within the inflamed gastrointestinal environment. In this work, we develop an engineered probiotic platform that is armed with biocatalytic and inflamed colon-targeting nanocoatings for multipronged management of IBD. Notably, we achieve the in situ growth of artificial nanocatalysts on probiotics through a bioinspired mineralization strategy. The resulting ferrihydrite nanostructures anchored on bacteria exhibit robust catalase-like activity across a broad pH range, effectively scavenging ROS to alleviate inflammation. The further envelopment with fucoidan-based shields confers probiotics with additional inflamed colon-targeting functions. Upon oral administration, the engineered probiotics display markedly improved viability and colonization within the inflamed intestine, and they further elicit boosted prophylactic and therapeutic efficacy against colitis through the synergistic interplay of nanocatalysis-based immunomodulation and probiotics-mediated microbiota reshaping. The robust and multifunctional probiotic platforms offer great potential for the comprehensive management of gastrointestinal disorders.

Uropathogenic Escherichia coli (UPEC) is the most common causative agent of urinary tract infection (UTI). UPEC invades bladder epithelial cells (BECs) via fusiform vesicles, escapes into the cytosol, and establishes biofilm-like intracellular bacterial communities (IBCs). Nucleoside-diphosphate kinase (NDK) is secreted by pathogenic bacteria to enhance virulence. However, whether NDK is involved in UPEC pathogenesis remains unclear. Here, we find that the lack of ndk impairs the colonization of UPEC CFT073 in mouse bladders and kidneys owing to the impaired ability of UPEC to form IBCs. Furthermore, we demonstrate that NDK inhibits caspase-1-dependent pyroptosis by consuming extracellular ATP, preventing superficial BEC exfoliation, and promoting IBC formation. UPEC utilizes the reactive oxygen species (ROS) sensor OxyR to indirectly activate the regulator integration host factor, which then directly activates ndk expression in response to intracellular ROS. Here, we reveal a signaling transduction pathway that UPEC employs to inhibit superficial BEC exfoliation, thus facilitating acute UTI.

Integrated wound care, a sequential process of promoting wound hemostasis, sealing, and healing, is of great clinical significance. However, the wet environment of wounds poses formidable challenges for integrated care. Herein, we developed an epidermal growth factor (EGF)-loaded, dehydrated physical microgel (DPM)-formed adhesive hydrogel for the integrated care of wet wounds. The DPMs were designed using the rational combination of hygroscopicity and reversible crosslinking of physical hydrogels. Unlike regular bioadhesives, which consider interfacial water as a barrier to adhesion, DPMs utilize water to form desirable adhesive structures. The hygroscopicity allowed the DPMs to absorb interfacial water and subsequently, the interfacial adhesion was realized by the interactions between tissue and DPMs. The reversible crosslinks further enabled DPMs to integrate into hydrogels (DPM-Gels), thus achieving wet adhesion. Importantly, the water-absorbing gelation mode of DPMs enabled facile loading of biologically active EGF to promote wound healing. We demonstrated that the DPM-Gels possessed wet tissue adhesive performance, with about 40 times the wet adhesive strength of fibrin glue and about 4 times the burst pressure of human blood pressure. Upon application at the injury site, the EGF-loaded DPM-Gels sequentially promoted efficient wound hemostasis, stable sealing, and quick healing, achieving integrated care of wet wounds.

Objective Optical fiber microphones hold significant practical value in applications like mine safety monitoring and disaster relief, where they must maintain stable performance despite external environmental interference. Many researchers have proposed diverse design schemes for optical fiber microphones, significantly enhancing their sensitivity, minimum detectable sound pressure, and directional recognition capabilities. However, there is still a lack of comprehensive research on the accuracy of continuous speech detection and the robustness of optical fiber microphone systems. These performance metrics are particularly critical in fields such as mine safety and disaster response. In environments like mines or disaster zones, not only must microphones be highly sensitive to capture low frequency or faint sounds, but also maintain stable performance amidst temperature fluctuations and other environmental factors. Moreover, speech signals in these scenarios are often complex and varied, demanding microphone systems with advanced signal processing capabilities to accurately discern key speech information. Therefore, it is essential to conduct robustness research on optical fiber microphones. Methods In this paper, we propose a highly stable optical fiber microphone sensing system based on polarization low coherence interferometry. The microphone designed for voice detection comprises a polyphenylene sulfide sensitive diaphragm and an optical fiber end face, forming a cross- correlation sensing system with a birefringent crystal based on polarization low coherence interferometry. By extracting the DC component of the interference signal through a birefringent crystal of known length, we effectively compensate for external environmental factors, thereby achieving high stability. Results and Discussions To evaluate the frequency response characteristics of the experimental scheme, we test the optical fiber microphone across a frequency range of 0.02 to 20.00 kHz. The results, depicted in Fig. 2, demonstrate that the optical fiber microphone system effectively detects sound signals within this range, maintaining a signal-to-noise- to- noise ratio (SNR) consistently above 50 dB across all frequencies. To assess its capability in detecting speech signals, we test continuous distress voice signals from both female and male subjects, as shown in Fig. 3. These findings highlight the system's 's accurate capture and reproduction of voice signals over a wide frequency spectrum. Long speech signals are also compared with those captured by a reference microphone. Furthermore, the system's 's performance under initial cavity length drift conditions is examined, with the outcomes presented in Fig. 6. These experiments illustrate the optical fiber microphone's 's robust adaptability and stability in scenarios involving output light source attenuation and initial cavity length drift. Conclusions We introduce a highly stable optical fiber microphone sensing system based on polarization low coherence interferometry in this paper. The microphone includes a sensitive diaphragm made of polyphenylene sulfide material and an optical fiber end face, along with a cross- correlated sensing system formed by custom birefringent crystals on three paths at the rear end. By extracting the direct current component of the interference signal through a birefringent crystal of known length, the system effectively compensates for external environmental factors and other irrelevant interferences, thereby strengthening system stability. Experimental results demonstrate a signal-to-noise- to- noise ratio of over 50 dB across the 0.02 to 20.00 kHz frequency range for this optical fiber microphone sensing system. Further detection and analysis of voice signals from different genders are conducted, followed by comparative analysis with a standard microphone. The system is also simulated under conditions of external environmental interference, where the initial cavity length of the sensor drifted by 1.631 mu m and the system input power attenuated by 60%. Compared to unchanged conditions, the cumulative distances of the system's output voice signals are 0.29073 and 0.28154, respectively, showcasing the voice detection stability of this optical fiber microphone. Given these characteristics, the proposed optical fiber microphone sensing system holds significant application potential in disaster warning, rescue operations, and other scenarios requiring highly stable voice detection. It accurately captures crucial voice information in complex and dynamic environments, providing essential technical support for safety monitoring and emergency response in critical areas.

Urinary tract infections are primarily caused by uropathogenic Escherichia coli (UPEC). UPEC infects bladder epithelial cells (BECs) via fusiform vesicles and escapes into the cytosol by disrupting fusiform vesicle membrane using outer membrane phospholipase PldA, and establishes biofilm-like intracellular bacterial communities (IBCs) for protection from host immune clearance. Cytosolic UPEC is captured by autophagy to form autophagosomes, then transported to lysosomes, triggering the spontaneous exocytosis of lysosomes. The mechanism by which UPEC evades autophagy to recognize and form IBCs remains unclear. Here, we demonstrate that by inhibiting autophagic flux, UPEC PldA reduces the lysosome exocytosis of BECs. By reducing intracellular phosphatidylinositol 3-phosphate levels, UPEC PldA increases the accumulation of NDP52 granules and decreases the targeting of NDP52 to autophagy, hence stalling preautophagosome structures. Thus, our results uncover a critical role for PldA to inhibit autophagic flux, favoring UPEC escapes from lysosome exocytosis, thereby contributing to acute urinary tract infection. This study uncovers a critical role of PldA through reducing intracellular PI3P levels to inhibit preautophagosomal structure maturation and autophagic flux, favoring UPEC escape from host lysosome exocytosis, thereby contributing to acute UTI.

Rheumatoid arthritis (RA) severely lowers the life quality by progressively destructing joint functions and eventually causing permanent disability, representing a pressing public health concern. The pathogenesis of RA includes the excessive production of proinflammatory cytokines and harmful oxygen-derived free radicals, such as nitric oxide (NO), which constitute vital targets for precise diagnosis and effective treatment of RA. In this study, we introduce an advanced nanoagent that integrates the RA microenvironment-activatable photoacoustic (PA) imaging with multitarget synergistic treatment for RA. A highly sensitive organic probe with NO-tunable energy transformation and molecular geometry is developed, which enables strong near-infrared absorption with a turn-on PA signal, and the active intramolecular motion could further boost PA conversion. The probe is coassembled with an inflammation-responsive prodrug to construct the theranostic nanoagent, on which a macrophage-derived cell membrane with natural tropism to the inflammatory sites is camouflaged to improve the targeting ability to inflamed joints. The nanoagent could not only sensitively detect RA and differentiate the severity but also efficiently alleviate RA symptoms and improve joint function. The combination of activatable probe-mediated NO scavenging and on-demand activation of anti-inflammatory prodrug significantly inhibits the proinflammatory factors and promotes macrophage repolarization from M1 to M2 phenotype. This meticulously designed nanoagent ingeniously integrates RA-specific PA molecular imaging with synergistic multitarget therapy, rendering tremendous promise for precise intervention of RA-related diseases.

Integrated wound care through sequentially promoting hemostasis, sealing, and healing holds great promise in clinical practice. However, it remains challenging for regular bioadhesives to achieve integrated care of dynamic wounds due to the difficulties in adapting to dynamic mechanical and wet wound environments. Herein, we reported a type of dehydrated, physical double crosslinked microgels (DPDMs) which were capable of in situ forming highly stretchable, compressible and tissue-adhesive hydrogels for integrated care of dynamic wounds. The DPDMs were designed by the rational integration of the reversible crosslinks and double crosslinks into micronized gels. The reversible physical crosslinks enabled the DPDMs to integrate together, and the double crosslinked characteristics further strengthen the formed macroscopical networks (DPDM-Gels). We demonstrated that the DPDM-Gels simultaneously possess outstanding tensile (∼940 kJ/m3) and compressive (∼270 kJ/m3) toughness, commercial bioadhesives-comparable tissue-adhesive strength, together with stable performance under hundreds of deformations. In vivo results further revealed that the DPDM-Gels could effectively stop bleeding in various bleeding models, even in an actual dynamic environment, and enable the integrated care of dynamic skin wounds. On the basis of the remarkable mechanical and appropriate adhesive properties, together with impressive integrated care capacities, the DPDM-Gels may provide a new approach for the smart care of dynamic wounds. STATEMENT OF SIGNIFICANCE: Integrated care of dynamic wounds holds great significance in clinical practice. However, the dynamic and wet wound environments pose great challenges for existing hydrogels to achieve it. This work developed robust adhesive hydrogels for integrated care of dynamic wounds by designing dehydrated, physical double crosslinked microgels (DPDMs). The reversible and double crosslinks enabled DPDMs to integrate into macroscopic hydrogels with high mechanical properties, appropriate adhesive strength and stable performance under hundreds of external deformations. Upon application at the injury site, DPDM-Gels efficiently stopped bleeding, even in an actual dynamic environment and showed effectiveness in integrated care of dynamic wounds. With the fascinating properties, DPDMs may become an effective tool for smart wound care.

Objective Sound source localization (SSL) technology is vital in a wide range of applications such as smart robots, unmanned aerial vehicle (UAV) detection, and unmanned driving. Acoustic sensor arrays are the main solution to SSL. However, with the development of small devices, it is difficult for these arrays to simultaneously satisfy the requirements of miniaturization and high precision. Inspired by small animals' auditory organs, bio-mimetic acoustic vector sensors are an alternative to acoustic sensor arrays. The parasitic fly Ormia ochracea inspires mechanical coupling between two membranes with an interaural phase difference (IPD) gain. Bio-mimetic acoustic vector sensors based on mechanical coupling inherit the IPD gain function. The gain effect of the current bio-mimetic acoustic vector sensors is limited to around the eigenfrequency. Meanwhile, electrical sensors are highly susceptible to extreme environments such as strong electromagnetic and high temperatures, while fiber-optic sensors can endure these conditions. We propose a flywheel-like fiber-optic Fabry-Perot (F-P) acoustic vector sensor for wide-range IPD gain based on the diaphragm coupling gain principle. We hope that the diaphragm-coupling fiber-optic F-P acoustic vector sensor can achieve the IPD gain of several kilohertz frequency ranges, adapting to ambiguous sound source direction in extreme environments. Methods The flywheel-coupling diaphragm is simplified to a two-degree-of-freedom (2-DOF) mass-spring-dashpot system with two shape modes of rocking mode and bending mode. COMSOL Multiphysics is employed to analyze diaphragm vibration characteristics and the structure parameters of the diaphragm are optimized based on the simulation results. The flywheel-coupling structure on stainless steel sheet is produced by ultraviolet laser etching technology. The adjoint spokes of two flywheel vibration units naturally couple to form a simplified intermembrane bridge coupling structure. The vibration units combined with individual fiber form independent fiber-optic F-P sensing units. The displacement of the vibration units changes the light intensity of the F-P sensing units detected by the intensity demodulation system. The intensity demodulation contains a tunable laser, 1x2 fiber splitter, optical circulators, photoelectric detectors, and data acquisition card (Fig. 8). The operating wavelength is determined in a common linear region of two sensors. The real-time IPD calculation is acquired by a phase-sensitive detection algorithm, and the incident angle of the sound wave is localized based on the IPD. The uncoupling two-sensor array is simultaneously subjected to SSL experiments to contrast with the flywheel-coupling acoustic vector sensor. Results and Discussions The proposed sensor has a wide frequency range of IPD gain. The rocking mode and bending mode eigenfrequency is simulated as 7. 2 kHz and 7. 6 kHz. The simulation results exhibit a significant gain in the frequency range of 5 kHz to 7. 4 kHz, with a maximum gain of 4. 5 at 7. 2 kHz (Fig. 4). The experimental results are in good agreement with simulations conducted in COMSOL Multiphysics (Fig. 10). The measured eigenfrequency is 7. 2 kHz and 7. 6 kHz with a slight discrepancy. The sensitivities of the sensing units are S-1 = 0. 24 V/Pa@7. 6 kHz and S-2 = 0. 21 V/Pa@7. 6 kHz. Two-dimensional planar SSL in - 90 degrees -90 degrees based on IPD cues is achieved (Fig. 11). The experiment results from 5 kHz to 7. 4 kHz present a wide frequency range IPD gain with a maximum gain of 5. 05 at 7. 2 kHz (Fig. 12). Cavity length and fiber end face inclination affect the spectrum of each sensing unit (Fig. 7). As a result, sensor consistency is difficult to achieve due to unavoidable processing errors. Since the phase-sensitive-detection algorithm is affected by noise, low signal-noise-ratio (SNR) signals may incur high localization errors. Both experimental and simulation results characterize that the sensor has a wide frequency range of IPD amplification effect. Conclusions We propose a flywheel-like fiber-optic F-P acoustic vector sensor for wide-range IPD gain based on the diaphragm coupling gain principle. The proposed flywheel-coupling diaphragm has two vibration modes of rocking and bending. The corresponding eigenfrequencies of 7. 2 kHz and 7. 6 kHz are calculated by COMSOL Multiphysics. The sensor has an obvious IPD amplification effect from 5 kHz to 7. 4 kHz in the frequency ranges. The maximum sensitivity and gain are acquired at 7. 2 kHz in the simulation. Cavity length and fiber end face inclination affect the spectrum of each sensing unit, limiting the SSL accuracy based on interaural intensity difference. Our paper applies a phase-sensitivedetection algorithm to obtain the phase difference between the two signals in real time. However, the method does not apply to low SNR signals. Meanwhile, the algorithm accuracy is affected by DC components, harmonics, and other factors. Finally, the scheme based on IPD is chosen and a flywheel-coupling diaphragm fiber-optic F-P acoustic vector sensor is fabricated. The first-order eigenfrequency is measured at around 7. 2 kHz. The structure achieves SSL with IPD gain in the frequency range from 5 kHz to 7. 4 kHz, compared with an uncoupling fiber-optic F-P acoustic sensor array. The measured maximum gain factor of 5. 05 is better than the simulation results. The maximum line size of the proposed sensor is smaller than the wavelength of the test acoustic wave to realize a miniaturized acoustic vector sensor with a simple structure and easy processing. The detection method using optical principles can be applied to satisfy SSL needs in extreme environments.

MicroRNAs (miRNAs) play vital roles in the post-transcriptional regulation of gene expression. Previous studies have shown that miR-150 is a crucial regulator of B cell proliferation, differentiation, metabolism, and apoptosis. miR-150 regulates the immune homeostasis during the development of obesity and is aberrantly expressed in multiple B-cell-related malignant tumors. Additionally, the altered expression of MIR-150 is a diagnostic biomarker of various autoimmune diseases. Furthermore, exosome-derived miR-150 is considered as prognostic tool in B cell lymphoma, autoimmune diseases and immune-mediated disorders, suggesting miR-150 plays a vital role in disease onset and progression. In this review, we summarized the miR-150-dependent regulation of B cell function in B cell-related immune diseases.

Injectable hydrogels that can withstand compressive and tensile forces hold great promise for preventing rebleeding in dynamic mechanical environments after emergency hemostasis of wounds. However, current injectable hydrogels often lack sufficient compressive or tensile performance. Here, a microstructure-united heterogeneous injectable hydrogel (MH) was constructed. The heterogeneous structure endowed MH with a unique "microstructures consecutive transmission" feature, which allowed it to exhibit high compressive and tensile performance simultaneously. In this work, two types of sodium alginate doped hydrogels with different microstructures were physically smashed into microgels, respectively. By mixing the microgels, MH with one micro-pores featured microstructure and another nano-pores featured microstructure can be formed. The obtained MH can withstand both compressive and tensile forces and showed high mechanical performance (compressive modulus: 345.67 ± 10.12 kPa and tensile modulus: 245.19 ± 7.82 kPa). Furtherly, MH was proven to provide stable and sustained hemostasis in the dynamic mechanical environment. Overall, this work provided an effective strategy for constructing injectable hydrogel with high compressive and tensile performance for hemostasis in dynamic mechanical environments.

Core decompression (CD) with mesenchymal stromal cells (MSCs) is an effective therapy for early-stage osteonecrosis of the femoral head (ONFH). Preconditioning of MSCs, using inflammatory mediators, is widely used in immunology and various cell therapies. We developed a three-dimensional printed functionally graded scaffold (FGS), made of β-TCP and PCL, for cell delivery at a specific location. The present study examined the efficacy of CD treatments with genetically modified (GM) MSCs over-expressing PDGF-BB (PDGF-MSCs) or GM MSCs co-over-expressing IL-4 and PDGF-BB and preconditioned for three days of exposure to lipopolysaccharide and tumor necrosis factor-alpha (IL-4-PDGF-pMSCs) using the FGS for treating steroid-induced ONFH in rabbits. We compared CD without cell-therapy, with IL-4-PDGF-pMSCs alone, and with FGS loaded with PDGF-MSCs or IL-4-PDGF-pMSCs. For the area inside the CD, the bone volume in the CD alone was higher than in both FGS groups. The IL-4-PDGF-pMSCs alone and FGS + PDGF-MSCs reduced the occurrence of empty lacunae and improved osteoclastogenesis. There was no significant difference in angiogenesis among the four groups. The combined effect of GM MSCs or pMSCs and the FGS was not superior to the effect of each alone. To establish an important adjunctive therapy for CD for early ONFH in the future, it is necessary and essential to develop an FGS that delivers biologics appropriately and provides structural and mechanical support.

BackgroundContinuous cross talk between MSCs and macrophages is integral to acute and chronic inflammation resulting from contaminated polyethylene particles (cPE); however, the effect of this inflammatory microenvironment on mitochondrial metabolism has not been fully elucidated. We hypothesized that (a) exposure to cPE leads to impaired mitochondrial metabolism and glycolytic reprogramming and (b) macrophages play a key role in this pathway.MethodsWe cultured MSCs with/without uncommitted M0 macrophages, with/without cPE in 3-dimensional gelatin methacrylate (3D GelMA) constructs/scaffolds. We evaluated mitochondrial function (membrane potential and reactive oxygen species-ROS production), metabolic pathways for adenosine triphosphate (ATP) production (glycolysis or oxidative phosphorylation) and response to stress mechanisms. We also studied macrophage polarization toward the pro-inflammatory M1 or the anti-inflammatory M2 phenotype and the osteogenic differentiation of MSCs.ResultsExposure to cPE impaired mitochondrial metabolism of MSCs; addition of M0 macrophages restored healthy mitochondrial function. Macrophages exposed to cPE-induced glycolytic reprogramming, but also initiated a response to this stress to restore mitochondrial biogenesis and homeostatic oxidative phosphorylation. Uncommitted M0 macrophages in coculture with MSC polarized to both M1 and M2 phenotypes. Osteogenesis was comparable among groups after 21 days.ConclusionThis work confirmed that cPE exposure triggers impaired mitochondrial metabolism and glycolytic reprogramming in a 3D coculture model of MSCs and macrophages and demonstrated that macrophages cocultured with MSCs undergo metabolic changes to maintain energy production and restore homeostatic metabolism.

With the emergence of various hydrogels with excellent functions, the air‐drying of hydrogels has attracted extensive attention. Improving the water retention capacity is critical in the application of hydrogels. Herein, inspired by the dense aggregation structure of natural hydrophilic macromolecules, hydrophilic substances (gelatin and glycerol) are first applied to enhance the water retention capacity of hydrogels by constructing a quenched double‐hydrophilic coating. The weight retention ratio of the modified hydrogels is increased to 72.5% at 25 °C and 40 RH% after 5 days. Furthermore, the construction of hydrophilic coating on the surface does not affect the mechanical properties, and the modified hydrogels still retain strong water retention capacity after loading. In addition, this approach is applicable to hydrogels with different shapes and types, and various materials can be selected. Therefore, the proposed method provides new insights for expanding the application scope and service life of hydrogels.