Modulating the Mesenchymal Stromal Cell Microenvironment Alters Exosome RNA Content and Ligament Healing Capacity.

Although mesenchymal stromal cell (MSC) based therapies hold promise in regenerative medicine, their clinical application remains challenging due to issues such as immunocompatibility. MSC-derived exosomes are a promising off-the-shelf therapy for promoting wound healing in a cell-free manner. However, the potential to customize the content of MSC-exosomes, and understanding how such modifications influence exosome effects on tissue regeneration remain underexplored. In this study, we used an in vitro system to compare the priming of human MSCs by two inflammatory inducers TNF-α and CRX-527 (a highly potent synthetic TLR4 agonist that can be used as a vaccine adjuvant or to induce anti-tumor immunity) on exosome molecular cargo, as well as on an in vivo rat ligament injury model to validate exosome potency. Different microenvironmental stimuli used to prime MSCs in vitro affected their exosomal microRNAs and mRNAs, influencing ligament healing. Exosomes derived from untreated MSCs significantly enhance the mechanical properties of healing ligaments, in contrast to those obtained from MSCs primed with inflammation-inducers, which not only fail to provide any improvement but also potentially deteriorate the mechanical properties. Additionally, a link was identified between altered exosomal microRNA levels and expression changes in microRNA targets in ligaments. These findings elucidate the nuanced interplay between MSCs, their exosomes, and tissue regeneration.

Effect of hydroxyethyl starch on drug stability and release of semaglutide in PLGA microspheres.

The degradation of peptide drugs limits the application of peptide drug microspheres. Structural changes of peptides at the water-oil interface and the destruction of their spatial structure in the complex microenvironment during polymer degradation can affect drug release and in vivo biological activity. This study demonstrates that adding hydroxyethyl starch (HES) to the internal aqueous phase (W1) significantly enhances the stability of semaglutide and optimizes its release behavior in PLGA microspheres. The results showed that this improvement was due to a spontaneous exothermic reaction (ΔH = -132.20 kJ mol-1) facilitated by hydrogen bonds. Incorporating HES into the internal aqueous phase using the water-in-oil-in-water (W1/O/W2) emulsion method yielded PLGA microspheres with a high encapsulation rate of 94.38 %. Moreover, microspheres with HES demonstrated well-controlled drug release over 44 days, unlike the slower and incomplete release in microspheres without HES. The optimized h-MG2 formulation achieved a more complete drug release (83.23 %) and prevented 30.65 % of drug loss compared to the HES-free microspheres within the same period. Additionally, the optimized semaglutide microspheres provided nearly three weeks of glycemic control with adequate safety. In conclusion, adding HES to the internal aqueous phase improved the in-situ drug stability and release behavior of semaglutide-loaded PLGA microspheres, effectively increasing the peptide drug payload in PLGA microspheres.

Review of the Perspectives and Study of Thermo-Responsive Polymer Gels and Applications in Oil-Based Drilling Fluids.

Thermoresponsive polymer gels are a type of intelligent material that can react to changes in temperature. These materials possess excellent innovative properties and find use in various fields. This paper systematically analyzes the methods for testing and regulating phase transition temperatures of thermo-responsive polymer gels based on their response mechanism. The report thoroughly introduces the latest research on thermo-responsive polymer gels in oil and gas extraction, discussing their advantages and challenges across various environments. Additionally, it elucidates how the application limitations of high-temperature and high-salt conditions can be resolved through process optimization and material innovation, ultimately broadening the scope of application of thermo-responsive polymer gels in oil and gas extraction. The article discusses the technological development and potential applications of thermo-responsive polymer gels in oil-based drilling fluids. This analysis aims to offer researchers in the oil and gas industry detailed insights into future possibilities for thermo-responsive polymer gels and to provide helpful guidance for their practical use in oil-based drilling fluids.

Modulating Mesenchymal Stromal Cell Microenvironment Alters Exosome RNA Content and Ligament Healing Capacity.

Although mesenchymal stromal cell (MSC) based therapies hold promise in regenerative medicine, their applications in clinical settings remain challenging due to issues such as immunocompatibility and cell stability. MSC-derived exosomes, small vesicles carrying various bioactive molecules, are a promising cell-free therapy to promote tissue regeneration. However, it remains unknown mainly regarding the ability to customize the content of MSC-derived exosomes, how alterations in the MSC microenvironment influence exosome content, and the effects of such modifications on healing efficiency and mechanical properties in tissue regeneration. In this study, we used an in vitro system of human MSC-derived exosomes and an in vivo rat ligament injury model to address these questions. We found a context-dependent correlation between exosomal and parent cell RNA content. Under native conditions, the correlation was moderate but heightened with microenvironmental changes. In vivo rat ligament injury model showed that MSC-derived exosomes increased ligament max load and stiffness. We also found that changes in the MSCs' microenvironment significantly influence the mechanical properties driven by exosome treatment. Additionally, a link was identified between altered exosomal microRNA levels and expression changes in microRNA targets in ligaments. These findings elucidate the nuanced interplay between MSCs, their exosomes, and tissue regeneration.

Impact of Hurricane Harvey on Inpatient Asthma Hospitalization Visits Within Southeast Texas, 2016-2019.

OBJECTIVE: The aim of the study is to estimate inpatient asthma hospital visit rates among impacted Texans in Public Health Region 6/5S during the year of and after Hurricane Harvey. METHODS: Asthma inpatient hospitalization discharges were collected from the Texas Health Care Information Collection database (2016-2019). RESULTS: Females (age-adjusted rates [AARs] = 4.8-5.0) and Black Texans (AARs = 5.0-8.1) experienced significantly higher AARs compared with males and White Texans during the year of and after Harvey. During the year of Hurricane Harvey, females were 1.49 times as likely to have an inpatient asthma visit compared with males, while Black Texans were 2.78 times as likely to have an inpatient asthma hospitalization compared with White Texans. CONCLUSIONS: Findings from this study may assist public health professionals and local officials to allocate future resources to the most impacted subgroups as well as establish effective processes to mitigate consequences.

The association of host and vector characteristics with Ctenocephalides felis pathogen and endosymbiont infection.

Surveillance of the fleas and flea-borne pathogens infecting cats is important for both human and animal health. Multiple zoonotic Bartonella and Rickettsia species are known to infect the most common flea infesting cats and dogs worldwide: Ctenocephalides felis, the cat flea. The ability of other flea species to transmit pathogens is relatively unexplored. We aimed to determine cat host and flea factors independently associated with flea Bartonella and Rickettsia infection. We also assessed flea and cat infection by flea-host pair and location. To accomplish these aims, we performed qPCR for the detection of Bartonella, hemotropic Mycoplasma, Rickettsia, and Wolbachia DNA using paired cat and flea samples obtained from free-roaming cats presenting for spay or neuter across four locations in the United States. A logistic regression model was employed to identify the effect of cat (sex, body weight, geographic location, and Bartonella, hemotropic Mycoplasma, and Rickettsia spp., infection) and flea (clade and Rickettsia and Wolbachia infection) factors on C. felis Bartonella clarridgeiae infection. From 189 free roaming cats, we collected 84 fleas: Ctenocephalides felis (78/84), Cediopsylla simplex (4/84), Orchopeas howardi (1/84), and Nosopsyllus fasciatus (1/84). Ctenocephalides felis were phylogenetically assigned to Clades 1, 4, and 6 by cox1 gene amplification. Rickettsia asembonensis (52/84) and B. clarridgeiae (16/84) were the most common pathogenic bacteria detected in fleas. Our model identified host cat sex and weight as independently associated with B. clarridgeiae infection in fleas. Rickettsia asembonensis (52/84), Rickettsia felis (7/84) and Bartonella henselae (7/84) were detected in specific clades: R. felis was detected only in Clades 1 and 6 while B. henselae and R. asembonensis were detected only in Clade 4. Wolbachia spp., also displayed clade specificity with strains other than Wolbachia wCfeT only infecting fleas from Clade 6. There was poor flea and host agreement for Bartonella spp., infection; however, there was agreement in the Bartonella species detected in cats and fleas by geographic location. These findings reinforce the importance of considering reservoir host attributes and vector phylogenetic diversity in epidemiological studies of flea-borne pathogens. Widespread sampling is necessary to identify the factors driving flea-borne pathogen presence and transmission.

[The Mechanism of Resveratrol on Acute T-Lymphocyte Leukemia through IL-7-Mediated JAK / STAT Signaling Pathway].

OBJECTIVE: To explore the roles and relative mechanism of resveratrol against T-ALL through detecting the signaling molecules in IL-7 and JAK/STAT pathway. METHODS: In vitro experiments, Molt4 cells were divided into 3 groups, including the control group, the DMSO group and resveratrol-treated group (Res group). The control group cells without any treatment, the DMSO group cells treated with 0.05% DMSO for 48 hours, the Res group cells treated with 200 µmol/L resveratrol for 48 hours. In vivo experiments, female C57BL/6J mice (6-8 weeks) were randomly divided into the control group, the T-ALL model group (T-ALL group), and Res treatment group (Res group). The control group mice treated with 0.05% DMSO by intragastric treatment, the T-ALL group mice treated with 0.05% DMSO by intragastric treatment, and the Res group mice treated with 10 mg/ml resveratrol. Expression of IL-7, IL-7R and Pim1 mRNA in the cells and mice spleen tissues were detected by RT-qPCR. Cell proliferation ability was detected by CCK-8. The expression of JAK1, JAK3, STAT5, phosphorylated JAK1 (p-JAK1), phosphorylated JAK3 (p-JAK3), phosphorylated STAT5 (p-STAT5) and Pim1 were detected by Western blot. ELISA was used to detect the IL-7 and IL-7R in the cells and mice serum of each groups. RESULTS: Resveratrol could inhibit the proliferation ability of Molt4 cells, decrease the relative levels of p-JAK1, p-JAK3, p-STAT5, Pim1 protein, and the expression levels of Pim1, IL-7 and IL-7R mRNA in cells and mice spleens, reduce the IL-7 and IL-7R in Molt4 cells and mice serum. CONCLUSION: Resveratrol may inhibite IL-7-medicated JAK/STAT signaling pathway to reduce the expression of target protein Pim1 to further exert its anti-T-ALL effects.

The effect of long-term methadone maintenance treatment on coupling among three large-scale brain networks in male heroin-dependent individuals: A resting-state fMRI study.

PURPOSE: Methadone maintenance treatment (MMT) is considered as an effective and mainstream therapy for heroin dependence. However, whether long-term MMT would improve the coupling among the three core large-scale brain networks (salience, default mode, and executive control) and its relationship with the craving for heroin is unknown. METHODS: Forty-four male heroin-dependent individuals during long-term MMT, 27 male heroin-dependent individuals after short-term detoxification/abstinence (SA), and 26 demographically matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging. We analyzed the difference in coupling among the salience, default mode, and executive control networks among the three groups and examined how the coupling among these large-scale networks was associated with craving before and after drug-cue exposure. RESULTS: Compared with the SA group, the MMT group showed lower craving before and after cue exposure and stronger connectivity between the dorsal anterior cingulate cortex (a key node of the salience network) and key regions of the bilateral executive control network, including the bilateral dorsolateral prefrontal cortex, posterior parietal cortex, and dorsomedial prefrontal cortex. Among the heroin-dependent individuals, the functional connectivity was negatively correlated with the craving before and after heroin-cue exposure. CONCLUSION: Our findings suggest that long-term MMT could increase the coupling between the salience and bilateral executive control networks and decrease craving for heroin. These findings contribute to the understanding of the neural mechanism of MMT, from the perspective of large-scale brain networks.

Abnormal brain oscillations and activation of patients with heroin use disorder during emotion regulation: The role of delta- and theta-band power.

BACKGROUND: Emotion dysregulation is a crucial component of substance use disorders in predisposition, maintenance, and relapse. Emotional regulation strategies are an important factor in emotion dysregulation. However, studies on heroin use disorder (HUD) patients' ability to use emotion regulation strategies are scarce. METHODS: Time-frequency-based analyses were used to compare the power of 33 patients with HUD and 28 healthy controls to elucidate whether patients with HUD have abnormal neural oscillations during passive viewing and emotion regulation strategies. Using the standardized low-resolution brain electromagnetic tomography algorithm (sLORETA), we estimated the possible sources of the anomalous band power. RESULTS: Compared to patients with HUD, healthy controls showed a stronger decrease in the power of the delta/theta band across all task conditions. The effect peaked at approximately 1300-1900 ms after stimulus onset and varied by task condition. The estimation of sLORETA suggested the frontal, parietal, and limbic lobes as possible generators. LIMITATIONS: We cannot exclude the potential influence of additional factors, such as sex, depression and anxiety levels, and polysubstance use, on the results. CONCLUSIONS: Patients with HUD have blunted arousal and impaired ability to use emotion regulation strategies. The abnormal patterns described above may be the underlying neurophysiological basis for this dysfunction. Future studies could combine different approaches to improve emotion dysregulation in patients with HUD to promote treatment outcomes.

Molecular Simulation of Interactions between High-Molecular-Polymer Flocculation Gel for Oil-Based Drilling Fluid and Clay Minerals.

China has abundant shale gas resources with great potential, which may serve as a significant support for the development of a "low-carbon economy". Domestic shale gas resources are buried deeply and difficult to exploit due to some prevalent issues, such as long horizontal sections, severe development of reservoir fractures, strong sensitivity to water, borehole instability, etc. Compared to water-based drilling fluids, oil-based drilling fluid exhibits better inhibition and good lubricity and is thus broadly used in shale gas drilling, but it is confronted with the challenge of removing the harmful solid phase. Selective chemical flocculation is one of the most effective methods of removing the harmful solid phase in oil-based drilling fluid. In this study, interactions between the flocculation gel for oil-based drilling fluid and clay minerals were investigated by molecular simulation, which revealed the molecular-scale selectivity of the flocculation gel for rock cuttings with negative charges. Calculations showed that the flocculation gel is highly effective for the flocculation of negatively charged cuttings, but it is ineffective for flocculating neutral cuttings. The flocculation gel is not very effective for cuttings with high hydrophilicity, and it is totally ineffective for flocculating cuttings with poor hydrophilicity. Within a limited concentration range, the flocculation effect can be enhanced by increasing the flocculation gel concentration. The performance of the flocculation gel declined at elevated temperatures.

Effect of landfill age on the physical and chemical characteristics of waste plastics/microplastics in a waste landfill sites.

The landfills store a lot of waste plastics, thus it has been confirmed a main source for the occurrence of plastics/microplastic. Although there are some reports that microplastics (MPs) can generate in leachate and refuse samples from the landfill, it exist many blanks for the evolution of physical and chemical characteristics of waste plastics and microplastics with different landfill age. To explore the process that large pieces of plastic are fractured into microplastics, the waste plastics with landfill age from 7 to 30 years are surveyed from a typical landfill in Shanghai. The results show that PE and PP are the most common types of landfilling plastics, and their chemical composition also have changed due to the creation of CO and -OH. Moreover, the crystallinity is affected by plastic type and landfill age. The crystallinity of PP increased from 24.9% to 56.8%, but for PE, the crystallinity decreased from 55.6% to 20.8%. The mechanical properties of waste plastics were reduced significantly, which may be caused by changes in carbon-chain molecules. Al, Ti, Co, and other metal elements were detected on the plastic surface. The hydrophobic behavior of waste plastic is constantly decreasing (102.2°-80.1°) under long-term landfilling. By investigating the changes in the physical and chemical characteristics of waste plastics with different landfill age can shed light upon the process of environmental weathering of waste plastics. This provide theoretical guidance for reducing the transport of microplastics to the environment.

Interface-engineered reduced graphene oxide assembly on nanofiber surface for high performance strain and temperature sensing.

Conductive polymer nanofiber composites (CPNCs) based wearable sensing electronics have aroused great attention of scientists in recent years. However, it is still difficult to obtain CPNCs with good water proof, excellent durability, and multiple sensing performance. Herein, we develop a multifunctional CPNC with a wrinkled reduced graphene oxide (RGO) shell and polymer nanofiber core, which is prepared by ultrasonication induced decoration of RGO onto the pre-stretched polyurethane (PU) nanofibers, followed by the release of the strain. The RGO assembly with a wrinkled structure not only greatly increases the surface roughness and thus the hydrophobicity but also enhances the strain sensing sensitivity (with a gauge factor of 154.8 in the strain range of 85%-100%) of the nanofibrous membrane. The obtained CPNC strain sensor also shows excellent sensing durability (over 1000 cycles) and can be used for body motion monitoring. The CPNC shows a negative temperature coefficient effect, which holds promising applications in high performance temperature sensors.

Vacancy Modulating Co3 Sn2 S2 Topological Semimetal for Aqueous Zinc-Ion Batteries.

Weyl semimetals (WSMs) with high electrical conductivity and suitable carrier density near the Fermi level are enticing candidates for aqueous Zn-ion batteries (AZIBs), meriting from topological surface states (TSSs). We propose a WSM Co3 Sn2 S2 cathode for AZIBs showing a discharge plateau around 1.5 V. By introducing Sn vacancies, extra redox peaks from the Sn4+ /Sn2+ transition appear, which leads to more Zn2+ transfer channels and active sites promoting charge-storage kinetics and Zn2+ storage capability. Co3 Sn1.8 S2 achieves a specific energy of 305 Wh kg-1 (0.2 Ag-1 ) and a specific power of 4900 Wkg-1 (5 Ag-1 ). Co3 Sn1.8 S2 and Znx Co3 Sn1.8 S2 benefit from better conductivity at lower temperatures; the quasi-solid Co3 Sn1.8 S2 //Zn battery delivers 126 mAh g-1 (0.6 Ag-1 ) at -30 °C and a cycling stability over 3000 cycles (2 Ag-1 ) with 85 % capacity retention at -10 °C.

HKUST-1 derived carbon adsorbents for tetracycline removal with excellent adsorption performance.

As the abuse of antibiotics has led to increasingly serious environmental pollution problems, studies have found that the adsorption method can be used to efficiently and quickly remove residual antibiotics in water with low cost and high efficiency. Metal-organic frameworks and their derived porous carbons have received widespread attention as a new type of adsorption material. In this study, HKUST-1 was synthesized by a hydrothermal method and carbonized to HDC-350 at 350 °C under an oxygen-free atmosphere. Through adsorption experiments, HDC-350 is found to show a superior adsorption effect for tetracycline (TC), with an adsorption capacity that reaches 136.88 mg g-1. The TC adsorption mechanism was studied through characterization and analysis of HDC-350. The adsorption of TC by HDC-350 mainly relies on electrostatic attraction, hydrogen bonding, metal-organic complexation, and intermolecular interactions. This study shows that HKUST-1-derived porous carbon can be used to improve the water stability of HKUST-1, and, at the same time, can effectively adsorb TC in solution, which provides good conditions for practical research applications in the future.

Superhydrophobic, electrically conductive and multifunctional polymer foam composite for chemical vapor detection and crude oil cleanup.

The leakage of chemicals (either vapors or liquids) severely threatens the environment and even people's health. It remains a great challenge to develop multifunctional and durable materials that can not only detect the chemical vapors but also clean up the liquid chemicals especially high viscous crude oil. Here, a superhydrophobic and conductive foam composite (SCFC) is prepared by decorating carbon black nanoparticles (CBNPs) onto the skeleton of the pre-swollen polymer foam under the assistance of ultrasonication. The CBNPs are firmly embedded onto the skeleton surface, exhibiting a strong interfacial adhesion and hence excellent surface stability and durability. The SCFC possesses stable vapor sensing behavior and can detect various chemical vapors with a low detection limit and good cycling performance. When used for oil/water separation, the SCFC has large oil adsorption capacity for different oils with excellent reusability. Also, the outstanding photo-thermal conversion performance of the SCFC can be used to significantly reduce the oil viscosity and hence realize efficient cleanup of the crude oil. The multifunctional SCFC has promising applications in the field of environment protection, flexible electronics, etc.

Airborne particulate matter, population mobility and COVID-19: a multi-city study in China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease, which has caused numerous deaths and health problems worldwide. This study aims to examine the effects of airborne particulate matter (PM) pollution and population mobility on COVID-19 across China. METHODS: We obtained daily confirmed cases of COVID-19, air particulate matter (PM2.5, PM10), weather parameters such as ambient temperature (AT) and absolute humidity (AH), and population mobility scale index (MSI) in 63 cities of China on a daily basis (excluding Wuhan) from January 01 to March 02, 2020. Then, the Generalized additive models (GAM) with a quasi-Poisson distribution were fitted to estimate the effects of PM10, PM2.5 and MSI on daily confirmed COVID-19 cases. RESULTS: We found each 1 unit increase in daily MSI was significantly positively associated with daily confirmed cases of COVID-19 in all lag days and the strongest estimated RR (1.21, 95% CIs:1.14 ~ 1.28) was observed at lag 014. In PM analysis, we found each 10 µg/m3 increase in the concentration of PM10 and PM2.5 was positively associated with the confirmed cases of COVID-19, and the estimated strongest RRs (both at lag 7) were 1.05 (95% CIs: 1.04, 1.07) and 1.06 (95% CIs: 1.04, 1.07), respectively. A similar trend was also found in all cumulative lag periods (from lag 01 to lag 014). The strongest effects for both PM10 and PM2.5 were at lag 014, and the RRs of each 10 µg/m3 increase were 1.18 (95% CIs:1.14, 1.22) and 1.23 (95% CIs:1.18, 1.29), respectively. CONCLUSIONS: Population mobility and airborne particulate matter may be associated with an increased risk of COVID-19 transmission.

The Post Hurricane Harvey Respiratory Protection Training Program.

OBJECTIVES: This study evaluated the effectiveness of an outreach program which included safety training and the distribution of personal protection kits in the Houston area in the aftermath of Hurricane Harvey. METHODS: Outreach: 71 volunteers conducted training sessions at 19 different sites and distributed a total of 1187 kits. Follow-up study: We conducted telephonic interviews to collect data on respiratory symptoms and obtain perceptions of the quality of the safety training provided among 83 participants. RESULTS: Participants reported an increase in airway symptoms four weeks after Hurricane Harvey. Outreach efforts were felt to be effective by a majority of participants. CONCLUSION: Future studies may adopt some of the best practices from our training efforts in terms of utilizing a combination of verbal demonstrations and written training guidelines on proper respirator usage.

Mitotic Implantation of the Transcription Factor Prospero via Phase Separation Drives Terminal Neuronal Differentiation.

Compacted heterochromatin blocks are prevalent in differentiated cells and present a barrier to cellular reprogramming. It remains obscure how heterochromatin remodeling is orchestrated during cell differentiation. Here we find that the evolutionarily conserved homeodomain transcription factor Prospero (Pros)/Prox1 ensures neuronal differentiation by driving heterochromatin domain condensation and expansion. Intriguingly, in mitotically dividing Drosophila neural precursors, Pros is retained at H3K9me3+ pericentromeric heterochromatin regions of chromosomes via liquid-liquid phase separation (LLPS). During mitotic exit of neural precursors, mitotically retained Pros recruits and concentrates heterochromatin protein 1 (HP1) into phase-separated condensates and drives heterochromatin compaction. This establishes a transcriptionally repressive chromatin environment that guarantees cell-cycle exit and terminal neuronal differentiation. Importantly, mammalian Prox1 employs a similar "mitotic-implantation-ensured heterochromatin condensation" strategy to reinforce neuronal differentiation. Together, our results unveiled a new paradigm whereby mitotic implantation of a transcription factor via LLPS remodels H3K9me3+ heterochromatin and drives timely and irreversible terminal differentiation.