Unveiling the Potential of Sulfur-Containing Gas Signaling Molecules in Acute Lung Injury: A Promising Therapeutic Avenue.

Acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), are pulmonary conditions that cause significant morbidity and mortality. The common etiologies of these conditions include pneumonia, pulmonary contusion, fat embolism, smoke inhalation, sepsis, shock, and acute pancreatitis. Inflammation, oxidative stress, apoptosis, and autophagy are key pathophysiological mechanisms underlying ALI. Hydrogen sulfide (H2S) and sulfur dioxide (SO2) are sulfur-containing gas signaling molecules that can mitigate these pathogenic processes by modulating various signaling pathways, such as toll-like receptor 4 (TLR4)/nod-like receptor protein 3 (NLRP3), extracellular signal-regulating protein kinase 1/2 (ERK1/2), mitogen-activated protein kinase (MAPK), phosphatidyl inositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), and nuclear factor kappa B (NF-κB), thereby conferring protection against ALI. Given the limited clinical effectiveness of prevailing ALI treatments, investigation of the modulation of sulfur-containing gas signaling molecules (H2S and SO2) in ALI is imperative. This article presents an overview of the regulatory pathways of sulfur-containing gas signaling molecules in ALI animal models induced by various stimuli, such as lipopolysaccharide, gas inhalation, oleic acid, and ischemia-reperfusion. Furthermore, this study explored the therapeutic prospects of diverse H2S and SO2 donors for ALI, stemming from diverse etiologies. The aim of the present study was to establish a theoretical framework, in order to promote the new treatment of ALI.

The interplay of hydrogen sulfide and microRNAs in cardiovascular diseases: insights and future perspectives.

Hydrogen sulfide (H2S) is recognized as the third gasotransmitter, after nitric oxide (NO) and carbon monoxide (CO). It is known for its cardioprotective properties, including the relaxation of blood vessels, promotion of angiogenesis, regulation of myocardial cell apoptosis, inhibition of vascular smooth muscle cell proliferation, and reduction of inflammation. Additionally, abnormal H2S generation has been linked to the development of cardiovascular diseases (CVD), such as pulmonary hypertension, hypertension, atherosclerosis, vascular calcification, and myocardial injury. MicroRNAs (miRNAs) are non-coding, conserved, and versatile molecules that primarily influence gene expression by repressing translation and have emerged as biomarkers for CVD diagnosis. Studies have demonstrated that H2S can ameliorate cardiac dysfunction by regulating specific miRNAs, and certain miRNAs can also regulate H2S synthesis. The crosstalk between miRNAs and H2S offers a novel perspective for investigating the pathophysiology, prevention, and treatment of CVD. The present analysis outlines the interactions between H2S and miRNAs and their influence on CVD, providing insights into their future potential and advancement.

A Study of the Drift Phenomena of Gate-Functionalized Biosensors and Dual-Gate-Functionalized Biosensors in Human Serum.

In this paper, we study the drift behavior of organic electrochemical transistor (OECT) biosensors in a phosphate-buffered saline (PBS) buffer solution and human serum. Theoretical and experimental methods are illustrated in this paper to understand the origin of the drift phenomenon and the mechanism of ion diffusion in the sensing layer. The drift phenomenon is explained using a first-order kinetic model of ion adsorption into the gate material and shows very good agreement with experimental data on drift in OECTs. We show that the temporal current drift can be largely mitigated using a dual-gate OECT architecture and that dual-gate-based biosensors can increase the accuracy and sensitivity of immuno-biosensors compared to a standard single-gate design. Specific binding can be detected at a relatively low limit of detection, even in human serum.

Selective Detection of Functionalized Carbon Particles based on Polymer Semiconducting and Conducting Devices as Potential Particulate Matter Sensors.

This paper reports a new mechanism for particulate matter detection and identification. Three types of carbon particles are synthesized with different functional groups to mimic the real particulates in atmospheric aerosol. After exposing polymer-based organic devices in organic field effect transistor (OFET) architectures to the particle mist, the sensitivity and selectivity of the detection of different types of particles are shown by the current changes extracted from the transfer curves. The results indicate that the sensitivity of the devices is related to the structure and functional groups of the organic semiconducting layers, as well as the morphology. The predominant response is simulated by a model that yielded values of charge carrier density increase and charge carriers delivered per unit mass of particles. The research points out that polymer semiconductor devices have the ability to selectively detect particles with multiple functional groups, which reveals a future direction for selective detection of particulate matter.

Blended Conjugated Host and Unconjugated Dopant Polymers Towards N-type All-Polymer Conductors and High-ZT Thermoelectrics.

N-Type thermoelectrics typically consist of small molecule dopant+polymer host. Only a few polymer dopant+polymer host systems have been reported, and these have lower thermoelectric parameters. N-type polymers with high crystallinity and order are generally used for high-conductivity ( σ ${\sigma }$ ) organic conductors. Few n-type polymers with only short-range lamellar stacking for high-conductivity materials have been reported. Here, we describe an n-type short-range lamellar-stacked all-polymer thermoelectric system with highest σ ${\sigma }$ of 78 S-1 , power factor (PF) of 163 µW m-1 K-2 , and maximum Figure of merit (ZT) of 0.53 at room temperature with a dopant/host ratio of 75 wt%. The minor effect of polymer dopant on the molecular arrangement of conjugated polymer PDPIN at high ratios, high doping capability, high Seebeck coefficient (S) absolute values relative to σ ${\sigma }$ , and atypical decreased thermal conductivity ( κ ${\kappa }$ ) with increased doping ratio contribute to the promising performance.

Aspirin/PLGA coated 3D-printed Ti-6Al-4V alloy modulate macrophage polarization to enhance osteoblast differentiation and osseointegration.

Although titanium (Ti) and Ti-based alloy have been widely used as dental and orthopedic implant materials, its bioinertness hindered the rapid osseointegration. Therefore, it is recommended to acquire ideal topographic and chemical characteristics through surface modification methods. 3D printing is a delicate manufacture technique which possesses superior controllability and reproducibility. While aspirin serve as a well-established non-steroidal anti-inflammatory agent. Recently, the importance of immune system in regulating bone dynamics has attracted increasing attention. We herein superimposed the aspirin/poly (lactic-co-glycolic acid) (ASP/PLGA) coating on the 3D-printed Ti-6Al-4V surface with uniform micro-structure to establish the Ti64-M-ASP/PLGA substrate. Scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS) and contact angle test confirmed the successful fabrication of the Ti64-M-ASP/PLGA substrate, with increased wettability and sustained release pattern of ASP. Compared with the Ti64 base material, the Ti64-M-ASP/PLGA substrate showed enhanced M2 and depressed M1 genes and proteins expressions in macrophages. The novel Ti64-M-ASP/PLGA substrate also displayed enhanced osteoblast proliferation, adhesion, extracellular mineralization ability and osteogenic gene expressions when cultured with macrophage conditioned medium in vitro. Furthermore, rat femora implantation model was used for in vivo evaluation. After 4 weeks of implantation, push out test, micro-computed tomography (micro-CT) and histological analyses all confirmed the superior osseointegration capabilities of the Ti64-M-ASP/PLGA implant than the other groups. Our study revealed the synergistic role played by 3D-printed micro topography and immunoregulatory drug aspirin in promoting osteogenesis in vitro and accelerating osseointegration in vivo, thus providing a promising method for better modifying the implant surface. Graphical abstract.

Negative auto-regulation of sulfur dioxide generation in vascular endothelial cells: AAT1 S-sulfenylation.

Recently, endogenous sulfur dioxide (SO2) has been found to exert an important function in the cardiovascular system. However, the regulatory mechanism for SO2 generation has not been entirely clarified. Hence, we aimed to explore the possible auto-regulation of endogenous SO2 generation and its mechanisms in vascular endothelial cells. We showed that SO2 did not affect the protein expression of aspartate aminotransferase 1 (AAT1), a major SO2 synthesis enzyme, but significantly inhibited AAT activity in primary human umbilical vein endothelial cells (HUVECs) and porcine purified AAT1 protein. An AAT1 enzymatic kinetic study showed that SO2 reduced the Vmax (1.89 ± 0.10 vs 2.55 ± 0.12, µmol/mg/min, P < 0.05) and increased the Km (35.97 ± 9.54 vs 19.33 ± 1.76 µmol/L, P < 0.05) values. Furthermore, SO2 induced S-sulfenylation of AAT1 in primary HUVECs and purified AAT1 protein. LC-MS/MS analysis indicated that SO2 sulfenylated AAT1 at Cys192. Mechanistically, thiol reductant DTT treatment or C192S mutation prevented SO2-induced AAT1 sulfenylation and the subsequent inhibition of AAT activity in purified AAT1 protein and primary HUVECs. Our findings reveal, for the first time, a mechanism of auto-regulation of SO2 generation through sulfenylation of AAT1 at Cys192 to suppress AAT activity in vascular endothelial cells. These findings will greatly deepen the understanding of regulatory mechanisms in the cardiovascular homeostasis.

Qiliqiangxin improves cardiac function and attenuates cardiac remodelling in doxorubicin-induced heart failure rats.

Context: Therapeutic doxorubicin administration is restricted as this anticancer drug may be cardiotoxic. The traditional Chinese medicine qiliqiangxin has been approved for clinical treatment of chronic heart failure.Objective: To explore the protective effects and molecular mechanisms of qiliqiangxin on doxorubicin-induced congestive heart failure (CHF) in rats.Materials and methods: A CHF rat model was established via intraperitoneal DOX injections (2.5 mg/kg/week) for 6 weeks. The rats were randomly assigned to control, CHF, CHF + QL (1.0 g/kg/d), or captopril (3.8 mg/kg/d) treatment groups (n = 10) for 4 weeks. MicroRNA sequencing elucidated the molecular mechanisms of qiliqiangxin on doxorubicin-induced CHF in rats.Results: Unlike in the CHF group, QL significantly reduced Bax:Bcl-2 (2.05 ± 0.23 vs. 0.94 ± 0.09, p < 0.05) and the levels of collagen I (0.19 ± 0.02 vs. 0.15 ± 0.01, p < 0.05), collagen III (0.19 ± 0.02 vs. 0.14 ± 0.02, p < 0.05), TGF-ß1 (5.28 ± 0.89 vs. 2.47 ± 0.51, p < 0.05), Smad3 (1.23 ± 0.12 vs. 0.78 ± 0.09, p < 0.05), MMP-2 (0.89 ± 0.01 vs. 0.53 ± 0.05, p < 0.05), and TIMP-2 (0.24 ± 0.03 vs. 0.44 ± 0.03, p < 0.05). QL also upregulated TGF-ß3 (0.65 ± 0.06 vs. 0.96 ± 0.10, p < 0.05) and Smad7 (0.09 ± 0.01 vs. 0.19 ± 0.023, p < 0.05). Moreover, Smad3 was a target of miR-345-3p.Discussion and Conclusions: The beneficial effects of QL on DOX-induced CHF in rats are mediated by reduction in myocardial fibrosis, promotion of TGF-ß3/Smad7, and inhibition of TGF-ß1/Smad3. QL may also modulate specific miRNAs. These results provide evidence that QL might be an effective treatment for DOX-induced CHF.

Nationwide Surveillance of Novel Oxazolidinone Resistance Gene optrA in Enterococcus Isolates in China from 2004 to 2014.

A total of 2,201 nonduplicate enterococcal isolates collected from 29 hospitals in 23 cities in China between 2004 and 2014 were screened for the oxazolidinone resistance gene optrA; 45 isolates (2.0%) were optrA positive with 11 OptrA variants identified. The positive rate of optrA increased from 0.4% to 3.9% during the 10-year surveillance period. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence type (MLST) analysis revealed that 37 optrA-positive Enterococcus faecalis isolates clustered into 25 PFGE patterns and 21 sequence types, while 6 Enterococcus faecium isolates represented 6 PFGE patterns and 6 sequence types. The present study underscores the importance of routine and persistent monitoring of oxazolidinone resistance and optrA gene.

Regulatory effects of hydrogen sulfide on the female reproductive system.

Hydrogen sulfide (H2S), a colorless exhaust gas, has been traditionally considered an air pollutant. However, recent studies have revealed that H2S functions as a novel gas signaling molecule, exerting diverse biological effects on various systems, including the cardiovascular, digestive, and nervous systems. Thus, H2S is involved in various pathophysiological processes. As H2S affects reproductive function, it has potential therapeutic implications in reproductive system diseases. This review examined the role of H2S in various female reproductive organs, including the ovary, fallopian tube, vagina, uterus, and placenta. Additionally, the regulatory function of H2S in the female reproductive system has been discussed to provide useful insights for developing clinical therapeutic strategies for reproductive diseases.

Role of hydrogen sulfide in the male reproductive system.

As an important gas signaling molecule, hydrogen sulfide (H2S) affects multiple organ systems, including the nervous, cardiovascular, digestive, and genitourinary, reproductive systems. In particular, H2S not only regulates female reproductive function but also holds great promise in the treatment of male reproductive diseases and disorders, such as erectile dysfunction, prostate cancer, varicocele, and infertility. In this review, we summarize the relationship between H2S and male reproductive organs, including the penis, testis, prostate, vas deferens, and epididymis. As lower urinary tract symptoms have a significant impact on penile erection disorders, we also address the potential ameliorative effects of H2S in erectile dysfunction resulting from bladder disease. Additionally, we discuss the regulatory role of H2S in cavernous smooth muscle relaxation, which involves the NO/cGMP pathway, the RhoA/Rho-kinase pathway, and K+ channel activation. Recently, various compounds that can alleviate erectile dysfunction have been reported to be at least partly dependent on H2S. Therefore, understanding the role of H2S in the male reproductive system may help develop novel strategies for the clinical treatment of male reproductive system diseases.

Post-translational modifications of p65: state of the art.

P65, a protein subunit of NF-κB, is a widely distributed transcription factor in eukaryotic cells and exerts diverse regulatory functions. Post-translational modifications such as phosphorylation, acetylation, methylation and ubiquitination modulate p65 transcriptional activity and function, impacting various physiological and pathological processes including inflammation, immune response, cell death, proliferation, differentiation and tumorigenesis. The intricate interplay between these modifications can be antagonistic or synergistic. Understanding p65 post-translational modifications not only elucidates NF-κB pathway regulation but also facilitates the identification of therapeutic targets and diagnostic markers for associated clinical conditions.

Therapeutic potential of hydrogen sulfide in osteoarthritis development.

The pathological mechanisms and treatments of osteoarthritis (OA) are critical topics in medical research. This paper reviews the regulatory mechanisms of hydrogen sulfide (H2S) in OA and the therapeutic potential of H2S donors. The review highlights the importance of changes in the endogenous H2S pathway in OA development and systematically elaborates on the role of H2S as a third gaseous transmitter that regulates inflammation, oxidative stress, and pain associated with OA. It also explains how H2S can lessen bone and joint inflammation by inhibiting leukocyte adhesion and migration, reducing pro-inflammatory mediators, and impeding the activation of key inflammatory pathways such as nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). Additionally, H2S is shown to mitigate mitochondrial dysfunction and endoplasmic reticulum stress, and to modulate Nrf2, NF-κB, PI3K/Akt, and MAPK pathways, thereby decreasing oxidative stress-induced chondrocyte apoptosis. Moreover, H2S alleviates bone and joint pain through the activation of Kv7, K-ATP, and Nrf2/HO-1-NQO1 pathways. Recent developments have produced a variety of H2S donors, including sustained-release H2S donors, natural H2S donors, and synthetic H2S donors. Understanding the role of H2S in OA can lead to the discovery of new therapeutic targets, while innovative H2S donors offer promising new treatments for patients with OA.

Therapeutic Potential of Hydrogen Sulfide in Reproductive System Disorders.

Hydrogen sulfide (H2S), previously regarded as a toxic exhaust and atmospheric pollutant, has emerged as the third gaseous signaling molecule following nitric oxide (NO) and carbon monoxide (CO). Recent research has revealed significant biological effects of H2S in a variety of systems, such as the nervous, cardiovascular, and digestive systems. Additionally, H2S has been found to impact reproductive system function and may have therapeutic implications for reproductive disorders. This paper explores the relationship between H2S and male reproductive disorders, specifically erectile dysfunction, prostate cancer, male infertility, and testicular damage. Additionally, it examines the impact of H2S regulation on the pathophysiology of the female reproductive system, including improvements in preterm birth, endometriosis, pre-eclampsia, fetal growth restriction, unexplained recurrent spontaneous abortion, placental oxidative damage, embryo implantation, recovery of myometrium post-delivery, and ovulation. The study delves into the regulatory functions of H2S within the reproductive systems of both genders, including its impact on the NO/cGMP pathway, the activation of K+ channels, and the relaxation mechanism of the spongy smooth muscle through the ROCK pathway, aiming to broaden the scope of potential therapeutic strategies for treating reproductive system disorders in clinical settings.

Sulfur signaling pathway in cardiovascular disease.

Hydrogen sulfide (H2S) and sulfur dioxide (SO2), recognized as endogenous sulfur-containing gas signaling molecules, were the third and fourth molecules to be identified subsequent to nitric oxide and carbon monoxide (CO), and exerted diverse biological effects on the cardiovascular system. However, the exact mechanisms underlying the actions of H2S and SO2 have remained elusive until now. Recently, novel post-translational modifications known as S-sulfhydration and S-sulfenylation, induced by H2S and SO2 respectively, have been proposed. These modifications involve the chemical alteration of specific cysteine residues in target proteins through S-sulfhydration and S-sulfenylation, respectively. H2S induced S-sulfhydrylation can have a significant impact on various cellular processes such as cell survival, apoptosis, cell proliferation, metabolism, mitochondrial function, endoplasmic reticulum stress, vasodilation, anti-inflammatory response and oxidative stress in the cardiovascular system. Alternatively, S-sulfenylation caused by SO2 serves primarily to maintain vascular homeostasis. Additional research is warranted to explore the physiological function of proteins with specific cysteine sites, despite the considerable advancements in comprehending the role of H2S-induced S-sulfhydration and SO2-induced S-sulfenylation in the cardiovascular system. The primary objective of this review is to present a comprehensive examination of the function and potential mechanism of S-sulfhydration and S-sulfenylation in the cardiovascular system. Proteins that undergo S-sulfhydration and S-sulfenylation may serve as promising targets for therapeutic intervention and drug development in the cardiovascular system. This could potentially expedite the future development and utilization of drugs related to H2S and SO2.

Post-translational modifications of Keap1: the state of the art.

The Keap1-Nrf2 signaling pathway plays a crucial role in cellular defense against oxidative stress-induced damage. Its activation entails the expression and transcriptional regulation of several proteins involved in detoxification and antioxidation processes within the organism. Keap1, serving as a pivotal transcriptional regulator within this pathway, exerts control over the activity of Nrf2. Various post-translational modifications (PTMs) of Keap1, such as alkylation, glycosylation, glutathiylation, S-sulfhydration, and other modifications, impact the binding affinity between Keap1 and Nrf2. Consequently, this leads to the accumulation of Nrf2 and its translocation to the nucleus, and subsequent activation of downstream antioxidant genes. Given the association between the Keap1-Nrf2 signaling pathway and various diseases such as cancer, neurodegenerative disorders, and diabetes, comprehending the post-translational modification of Keap1 not only deepens our understanding of Nrf2 signaling regulation but also contributes to the identification of novel drug targets and biomarkers. Consequently, this knowledge holds immense importance in the prevention and treatment of diseases induced by oxidative stress.

TCPP/MgO-loaded PLGA microspheres combining photodynamic antibacterial therapy with PBM-assisted fibroblast activation to treat periodontitis.

Bacteria eradication and subsequent periodontal tissue reconstruction is the primary task for periodontitis treatment. Commonly used antibiotic therapy suffers from antibiotic resistance. Meanwhile, promoting fibroblast activity is crucial for re-establishing a damaged periodontal structure. In addition to the fibroblast activation property of Mg2+, photobiomodulation (PBM) has recently attracted increasing attention in wound healing. Using the same 635 nm laser resource, PBM could simultaneously work with antibacterial photodynamic therapy (aPDT) to achieve antibacterial function and fibroblast activation effect. Herein, multifunctional microspheres were designed by employing poly (lactic-co-glycolic acid) (PLGA) microspheres to load tetrakis (4-carboxyphenyl) porphyrin (TCPP) and magnesium oxide (MgO) nanoparticles, named as PMT, with sustained Mg2+ release for 20 days. PMT achieved excellent antibacterial photodynamic effect for periodontal pathogens F. nucleatum and P. gingivalis by generating reactive oxygen species, which increases cell membrane permeability and destroys bacteria integrity to cause bacteria death. Meanwhile, PMT itself exhibited improved fibroblast viability and adhesion, with the PMT + light group revealing further activation of fibroblast cells, suggesting the coordinated action of Mg2+ and PBM effects. The underlying molecular mechanism might be the elevated gene expressions of Fibronectin 1, Col1a1, and Vinculin. In addition, the in vivo rat periodontitis model proved the superior therapeutic effects of PMT with laser illumination using micro-computed tomography analysis and histological staining, which presented decreased inflammatory cells, increased collagen production, and higher alveolar bone level in the PMT group. Our study sheds light on a promising strategy to fight periodontitis using versatile microspheres, which combine aPDT and PBM-assisted fibroblast activation functions.

Sensitive organic electrochemical transistor biosensors: Comparing single and dual gate functionalization and different COOH-functionalized bioreceptor layers.

We developed new measurement configurations based on organic electrochemical transistors (OECTs). Three types of COOH-functionalized bioreceptor layers were deposited on indium tin oxide (ITO) electrodes on poly(ethylene terephthalate) (PET) substrates and their performance was tested using single gate functionalization organic electrochemical transistor (S-OECT) and dual gate functionalization organic electrochemical transistor (D-OECT) configurations. The three layers included one p-type semiconductor, one insulator, and one self-assembled layer, and the dual gates were connected in series through buffer solutions, so the solution-electrode interfaces had the opposite polarities. We investigated the sensitivities of these systems using the human IgG antigen-human IgG antibody receptor pair for main experiments, and drifts of antibody-functionalized gates without analytes as control experiments. Drifts without analyte can obscure the real sensitivity. We show that the D-OECT has the capability to cancel the drifts, and is also beneficial for showing the sensitivity more exactly. This configuration has the ability to increase the accuracy of antibody-antigen interaction detection, and further decrease or eliminate the effect of ions in the buffer solution. We also prove that the D-OECT can work well with different bioreceptor materials, which indicates that the system can be further applied to different conditions.

Photothermal-Controlled Release of IL-4 in IL-4/PDA-Immobilized Black Titanium Dioxide (TiO2) Nanotubes Surface to Enhance Osseointegration: An In Vivo Study.

Host immune response has gradually been accepted as a critical factor in achieving successful implant osseointegration. The aim of this study is to create a favorable immune microenvironment by the dominant release of IL-4 during the initial few days after implant insertion to mitigate early inflammatory reactions and facilitate osseointegration. Herein, the B-TNT/PDA/IL-4 substrate was established by immobilizing an interleukin-4 (IL-4)/polydopamine (PDA) coating on a black TiO2 nanotube (B-TNT) surface, achieving on-demand IL-4 release under near infrared (NIR) irradiation. Gene Ontology (GO) enrichment analyses based on high-throughput DNA microarray data revealed that IL-4 addition inhibited osteoclast differentiation and function. Animal experiment results suggested that the B-TNT/PDA/IL-4+Laser substrate induced the least inflammatory, tartrate-resistant acid phosphatase, inducible nitric oxide synthase and the most CD163 positive cells, compared to the Ti group at 7 days post-implantation. In addition, 28 days post-implantation, micro-computed tomography results showed the highest bone volume/total volume, trabecular thickness, trabecular number and the lowest trabecular separation, while Hematoxylin-eosin and Masson-trichrome staining revealed the largest amount of new bone formation for the B-TNT/PDA/IL-4+Laser group. This study revealed the osteoimmunoregulatory function of the novel B-TNT/PDA/IL-4 surface by photothermal release of IL-4 at an early period post-implantation, thus paving a new way for dental implant surface modification.