Oxygen is an essential gasotransmitter directly sensed via protein gasoreceptors

The current restrictive criteria for gasotransmitters exclude oxygen(O_(2))as a gasotransmitter in vertebrates.In this manuscript,I propose a revision of gasotransmitter criteria to include O_(2) per se as a signaling molecule and'essential gasotransmitter'for vertebrates.This revision would enable us to search for protein-based O_(2)-binding sensors(gasoreceptors)in all cells in the brain or other tissues rather than specialized tissues such as the carotid body or gills.If microorganisms have protein-based O_(2)-binding sensors or gasoreceptors such as DosP or FixL or FNR with diverse signaling domains,then eukaryotic cells must also have O_(2)-binding sensors or gasoreceptors.Just as there are proteinbased receptor(s)for nitric oxide(GUCY1A,GUCY1B,CLOCK,NR1D2)in cells of diverse tissues,it is reasonable to consider that there are protein-based receptors for O_(2) in cells of diverse tissues as well.In mammals,O_(2) must be acting as a gasotransmitter or gaseous signaling molecule via protein-based gasoreceptors such as androglobin that very likely mediate acute sensing of O_(2).Accepting O_(2) as an essential gasotransmitter will enable us to search for gasoreceptors not only for O_(2) but also for other nonessential gasotransmitters such as hydrogen sulfide,ammonia,methane,and ethylene.It will also allow us to investigate the role of environment-derived metal ions in acute gas(or solute)sensing within and between organisms.Finally,accepting O_(2) per se as a signaling molecule acting via gasoreceptors will open up the field of gasocrinology.

Bamboo‑Inspired Gasotransmitter Microfibres for Wound Healing

Diabetic wounds have become a major clinical problem that cannot be ignored.Gases,such as hydrogen sulphide(H_(2)S),have demonstrated value in inducing angiogenesis and accelerating wound healing,while their effective delivery is still challenging.Here,inspired by the continuous-independent hollow structure of bamboo,we propose novel gasotransmitter microfibres with septal H_(2)S bubbles using microfluidic spinning for diabetic wound healing.Benefitting from the exact control of microfluidics,gasotransmitter microfibres with different bubble sizes and morphologies could be generated successfully and continuously.Under the dual effects of drugs in the shell and gas in the core,the wound healing process could be accelerated.Furthermore,the controllable release of drugs could be achieved by adding responsive materials into the microfiber shell,which would promote continuous effects of contents on demand.Based on in vitro and in vivo stud-ies,we have proven that these gasotransmitter microfibres have a positive impact on inducing angiogenesis and promoting cell proliferation during wound healing.Thus,it is believed that the bamboo-inspired gasotransmitter microfibres will have important value in gasotransmitter research and clinical applications.

Hydrogen Sulfide Promotes Adipocyte Differentiation, Hyperplasia, and Hypertrophy

Hydrogen sulfide (H2S) is endogenously produced in adipocytes and fat tissues and stimulates adipogenesis. The integrated pathogenic effects of H2S on the development of obesity and the underlying mechanisms, however, have been unclear. Here, we find that a decreased endogenous H2S level lowered lipid accumulation in mouse adipocytes. Exogenous H2S treatment significantly increased the adipogenesis of primary mouse preadipocytes after six days of adipogenic induction. In the early phase of adipogenesis, H2S increased cell proliferation and prepared cells to go through hyperplasia. After H2S treatment for ten days, preadipocytes exhibited significantly greater cell surface area and diameter, indicating cell hypertrophy. Although it stimulated lipid accumulation and adipogenesis, H2S had no effect on lipolysis. With nutrition overload and high glucose/insulin incubation, H2S further stimulated glucose consumption and deteriorated adipocyte hypertrophy. H2S upregulated hyperplasia genes (CCAAT/enhancer-binding protein (C/EBPβ), cell division cycle 25 (Cdc25), minichromosome maintenance 3 (Mcm3), and cell division cycle 45 (Cdc45)) and cyclin-dependent kinase 2 protein (Cdk2), which regulates cell proliferation. H2S also upregulated the insulin receptor β (Irβ)-activated mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) pathways, leading to adipogenesis. In conclusion, H2S increases adipocyte differentiation, hypertrophy, and hyperplasia, implying that it plays a pathogenic role in obesity disorder.

Click chemistry and drug delivery:A bird's-eye view

Click chemistry has been proven to be very useful in drug delivery.Due to the availability of a large number of click reactions with a various characteristics,selection of appropriate chemistry for a given application is often not a trivial task.This review is written for pharmaceutical researchers who are interested in click chemistry applications and yet may not be click chemistry experts.For this,the review gives an overview of available click reactions organized by application types.Further,the general understanding of click reactions being fast and high yielding sometimes overshadows the need to analyze reaction kinetics in assessing suitability of a given reaction for certain applications.For this,we highlight the need to analyze the relationship among reaction kinetics,concentration effects,and reaction time scales,knowing that lack of such analysis could easily lead to failures.Further,possible issues such as chemical stability with various click reagents are also discussed to aid experimental designs.Recent examples and extensive references are also provided to aid in-depth understanding of technical details.We hope this review will help those interested in using click chemistry in drug delivery to select the appropriate reactions/reagents and minimize the number of pitfalls.

Surface charge adaptive nitric oxide nanogenerator for enhanced photothermal eradication of drug-resistant biofilm infections

Due to protection of extracellular polymeric substances,the therapeutic efficiency of conventional antimicrobial agents is often impeded by their poor infiltration and accumulation in biofilm.Herein,one type of surface charge adaptable nitric oxide(NO)nanogenerator was developed for biofilm permeation,retention and eradication.This nanogenerator(PDG@Au-NO/PBAM)is composed of a core-shell structure:thermo-sensitive NO donor conjugated AuNPs on cationic poly(dopamine-co-glucosamine)nanoparticle(PDG@Au-NO)served as core,and anionic phenylboronic acid-acryloylmorpholine(PBAM)copolymer was employed as a shell.The NO nanogenerator featured long circulation and good biocompatibility.Once the nanogenerator reached acidic biofilm,its surface charge would be switched to positive after shell dissociation and cationic core exposure,which was conducive for the nanogenerator to infiltrate and accumulate in the depth of biofilm.In addition,the nanogenerator could sustainably generate NO to disturb the integrity of biofilm at physiological temperature,then generate hyperthermia and explosive NO release upon NIR irradiation to efficiently eradicate drug-resistant bacteria biofilm.Such rational design offers a promising approach for developing nanosystems against biofilm-associated infections.

Hydrogen sulfide, a signaling molecule in plant stress responses

Gaseous molecules, such as hydrogen sulfide(H_2S)and nitric oxide(NO), are crucial players in cellular and(patho)physiological processes in biological systems. The biological functions of these gaseous molecules, which were first discovered and identified as gasotransmitters in animals, have received unprecedented attention from plant scientists in recent decades. Researchers have arrived at the consensus that H_2S is synthesized endogenously and serves as a signaling molecule throughout the plant life cycle.However, the mechanisms of H_2S action in redox biology is still largely unexplored. This review highlights what we currently know about the characteristics and biosynthesis of H_2S in plants. Additionally,we summarize the role of H_2S in plant resistance to abiotic stress. Moreover, we propose and discuss possible redox-dependent mechanisms by which H_2S regulates plant physiology.

Nature’s marvels endowed in gaseous molecules Ⅰ:Carbon monoxide and its physiological and therapeutic roles

Nature has endowed gaseous molecules such as O_(2),CO_(2),CO,NO,H2 S,and N2 with critical and diverse roles in sustaining life,from supplying energy needed to power life and building blocks for life ’s physical structure to mediating and coordinating cellular functions.In this article,we give a brief introduction of the complex functions of the various gaseous molecules in life and then focus on carbon monoxide as a specific example of an endogenously produced signaling molecule to highlight the importance of this class of molecules.The past twenty years have seen much progress in understanding CO’s mechanism(s) of action and pharmacological effects as well as in developing delivery methods for easy administration.One remarkable trait of CO is its pleiotropic effects that have few parallels,except perhaps its sister gaseous signaling molecules such as nitric oxide and hydrogen sulfide.This review will delve into the sophistication of CO-mediated signaling as well as its validated pharmacological functions and possible therapeutic applications.

CO as a therapeutic agent: discovery and delivery forms

Carbon monoxide(CO) as one of the three important endogenously produced signaling molecules, termed as "gasotransmitter," has emerged as a promising therapeutic agent for treating various inflammation and cellular-stress related diseases. In this review, we discussed CO’s evolution from a well-recognized toxic gas to a signaling molecule, and the effort to develop different approaches to deliver it for therapeutic application. We also summarize recently reported chemistry towards different CO delivery forms.

Hydrogen sulfide,nitric oxide,and neurodegenerative disorders

Hydrogen Sulfide(H_(2)S)and Nitric Oxide(NO)have become recognized as important gaseous signaling molecules with enormous pharmacological effects,therapeutic value,and central physiological roles.NO is one of the most important regulators of the pathophysiological condition in central nervous system(CNS).It is critical in the various functioning of the brain;however,beyond certain concentration/level,it is toxic.H_(2)S was regarded as toxic gas with the smell like rotten egg.But,it is now regarded as emerging neuroprotectant and neuromodulator.Recently,the use of donors and inhibitors of these signaling molecules have helped us to identify their accurate and precise biological effects.The most abundant neurotransmitter of CNS(glutamate)is the initiator of the reaction that forms NO,and H_(2)S is highly expressed in brain.These molecules are shedding light on the pathogenesis of various neurological disorders.This review is mainly focused on the importance of H_(2)S and NO for normal functioning of CNS.

Advances in the study on endogenous sulfur dioxide in the cardiovascular system

Objective This review summarized the current advances in understanding the role of the novel gasotransmitter,sulfur dioxide （SO2）,in the cardiovascular system.Data sources Articles on the advances in the study of the role of endogenous sulfur dioxide in the cardiovascular system were accessed from PubMed and CNKI from 2003 to 2013,using keywords such as ＂endogenous sulfur dioxide＂ and ＂cardiovascular system＂.Study selection Articles with regard to the role of SO2 in the regulation of cardiovascular system were selected.Results Recently,scientists discovered that an endogenous SO2 pathway is present in the cardiovascular system and exerts physiologically significant effects,such as regulation of the cardiac function and the pathogenesis of various cardiopulmonary diseases such as hypoxic pulmonary hypertension,hypertension,coronary atherosclerosis,and cardiac ischemia-reperfusion （I/R） injury,in the cardiovascular system.Conclusions Endogenous SO2 is a novel member of the gasotransmitter family in addition to the nitric oxide （NO）,carbon monoxide （CO）,and hydrogen sulfide （H2S）.Studies indicated that it has a role in regulating the cardiovascular disease.

Hydrogen sulfide prodrugs—a review

Hydrogen sul fi de(H_2S) is recognized as one of three gasotransmitters together with nitric oxide(NO) and carbon monoxide(CO). As a signaling molecule, H_2S plays an important role in physiology and shows great potential in pharmaceutical applications. Along this line, there is a need for the development of H_2S prodrugs for various reasons. In this review, we summarize different H_2S prodrugs, their chemical properties, and some of their potential therapeutic applications.