This is a working overview of freeze-thaw, written for readers who want more than a one-paragraph summary but less than a textbook.
This page was last updated on 2026-03-19 and is reviewed periodically as new material appears.
Development is attributed to researchers at the Institute of Molecular Genetics in Moscow during the early 1980s, building on earlier Soviet work with ACTH fragments. Russian regulatory approval followed for intranasal use, and the compound has remained commercially available there for decades. Most published human data originate from Russian and, later, some Eastern European clinical reports, which are not always accessible in English translation. Outside that region the material is generally handled as a research chemical rather than a licensed medicine.
Regulatory status differs sharply between jurisdictions. In Russia the peptide is registered as a prescription nasal preparation, while agencies such as the United States Food and Drug Administration have not approved it for any indication. Products sold elsewhere are typically labeled for laboratory research only, and such labels shift responsibility for safe handling to the purchaser. Because the same name covers pharmaceutical-grade nasal drops and bulk research powder, identity and purity documentation becomes the main practical concern when comparing sources.
Pharmacokinetic accounts emphasize rapid breakdown. After intravenous dosing the intact peptide disappears from blood within minutes, and nasal delivery produces low but measurable concentrations. Metabolites rather than the parent molecule may account for part of the observed activity, although the relative contribution is unresolved. Dosing in the literature varies widely and no optimal schedule has been agreed. These gaps are regularly cited as a reason the findings have not produced broad clinical adoption beyond the original research setting.
Proposed mechanisms center on neurotrophic signaling rather than on classical melanocortin receptor activation. Rodent experiments have reported shifts in the expression of brain-derived neurotrophic factor and nerve growth factor after administration, together with changes in the associated receptor systems. Several authors argue that the peptide acts largely through its degradation products and their interaction with peptidergic pathways, but this remains a hypothesis rather than a settled finding. No single molecular target has been identified in a way that the field broadly accepts.
Published research covers ischemic stroke, traumatic brain injury, cognitive impairment, optic nerve conditions and attention-related measures. Much of the human evidence comes from small trials conducted in one country, which limits how far the results generalize. Animal models supply the larger share of the data, and effects seen in rodents do not transfer automatically to people. Reviews have noted that methodological reporting is often incomplete, making it difficult to pool results or compare treatment schedules across studies.
| Property | Value | Notes |
|---|---|---|
| Chemical class | Synthetic heptapeptide (ACTH fragment analog) | Not a steroid; does not belong to the melanocortin agonist drugs by marketing category |
| Molecular formula | C37H51N9O10S (commonly cited) | Reported values vary slightly with salt and counter-ion content |
| Appearance | White to off-white lyophilized powder | A single batch may appear as a loose cake or fluffy solid |
| Solubility | Freely soluble in water and aqueous buffer | Stock solutions are usually prepared in sterile water or saline |
| Typical storage | −20 °C or below, desiccated and protected from light | Seal opened vials promptly to limit moisture uptake |
The proposed mechanism centres on neurotrophic signalling rather than direct receptor activation. Semax is reported to increase expression of brain-derived neurotrophic factor and nerve growth factor in several brain regions, and to shift the balance between excitatory and inhibitory neurotransmitter systems. Interaction with melanocortin receptors has been suggested because of the parent ACTH fragment. Many of these findings come from rodent studies, and the extent to which they translate to human physiology remains an open question.
Scientific literature on semax is unevenly distributed. A substantial share of published work originates from a small number of laboratories in Russia, while independent replication elsewhere is limited. Human data consist mostly of small trials with short follow-up, and several reported outcomes rely on subjective rating scales. Questions about how much intact peptide reaches the central nervous system after nasal administration, and how long it persists there, are still unresolved. The compound is best described as an active research subject rather than a settled pharmacological agent.
Semax is supplied as a lyophilized powder that appears white to off-white. It dissolves readily in water, phosphate-buffered saline, and other aqueous media, which simplifies preparation of working solutions for laboratory use. The nasal products registered in Russia are dilute aqueous solutions, typically around 0.1 percent peptide by weight. Organic solvents are rarely necessary and can complicate handling. Because the peptide is hygroscopic, weighing should be performed quickly and with minimal exposure to ambient humidity.
Solid material is normally kept at minus 20 degrees Celsius in a sealed, desiccated container. Reconstituted solutions are less stable and are usually divided into single-use aliquots before freezing. Repeated freeze-thaw cycles are avoided because they promote aggregation and loss of activity. Light exposure is minimized by using amber glassware or foil wrapping. Published stability data for this peptide are sparse, so recommended storage conditions rest mainly on general practice for short synthetic peptides rather than on dedicated study.
Repotrectinib, sold under the brand name Augtyro, is an anti-cancer medication used for the treatment of non-small cell lung cancer. It is taken by mouth. Repotrectinib is an inhibitor of proto-oncogene tyrosine-protein kinase ROS1 (ROS1) and of the tropomyosin receptor tyrosine kinases (TRKs) TRKA, TRKB, and TRKC. The most common adverse reactions include dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive disorders, and muscular weakness. Repotrectinib was approved for medical use in the United States in November 2023, and in the European Union in January 2025.
In addition, proteins released from cells can impede protein C activation, for example eosinophil, which may explain thrombosis in hypereosinophilic heart disease. Protein C may be up-regulated by platelet factor 4. This cytokine is conjectured to improve activation of protein C by forming an electrostatic bridge from protein C's Gla domain to the glycosaminoglycan (GAG) domain of thrombomodulin, reducing the Michaelis constant (KM) for their reaction. In addition, Protein C is inhibited by protein C inhibitor.
Thermoresponsive polymers can be used as the stationary phase in liquid chromatography. Here, the polarity of the stationary phase can be varied by temperature changes, altering the power of separation without changing the column or solvent composition. Thermally related benefits of gas chromatography can now be applied to classes of compounds that are restricted to liquid chromatography due to their thermolability. In place of solvent gradient elution, thermoresponsive polymers allow the use of temperature gradients under purely aqueous isocratic conditions. The versatility of the system is controlled not only by changing temperature, but also by adding modifying moieties that allow for a choice of enhanced hydrophobic interaction, or by introducing the prospect of electrostatic interaction. These developments have already brought major improvements to the fields of hydrophobic interaction chromatography, size exclusion chromatography, ion exchange chromatography, and affinity chromatography separations, as well as pseudo-solid phase extractions ("pseudo" because of phase transitions).
[L] should be read as "the concentration of L" and likewise for the other terms in square brackets. The expression can be greatly simplified by removing those terms which are constant. The number of water molecules attached to each metal ion is constant. In dilute solutions the concentration of water is effectively constant. The expression becomes
The attachment of fluorescent group on one head of the molecule confers contrast properties. A new strategy to enhance the cellular up-take capacity of CPP is based on association of polycationic and polyanionic domains that are separated by a linker. Cellular association of polycationic residues (polyarginine) with negatively charged membrane cells is effectively blocked by the presence of polyanionic residue (poly-glutamic acid) and the linker, which confer the proper distance between these two charged residues in order to maximize their interaction. These peptides adopt hairpin structure, confirmed by overhauser effect correlation for proton-proton proximities of the two charged moieties. At this stage only the linker is exposed to protease hydrolysis in vivo applications. The linker hydrolysis occur and the two charged fragments experience more conformational freedom. In the absence of linker, the cationic peptide can interact more efficient with the target cell and cellular uptake occurs before proteolysis. This strategy found applications in labeling tumor cells in vivo. Tumor cells were marked in minutes. Linker degradation can be predicted by the amount of D-aminoacids (the unnatural isomer) incorporated in the peptide chain, this restricts in vivo proteolysis to the central linker.
Sources: en.wikipedia.org
Metabolomics is the scientific study of chemical processes involving metabolites, the small molecule substrates, intermediates, and products of cell metabolism. Specifically, metabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind", the study of their small-molecule metabolite profiles. The metabolome represents the complete set of metabolites in a biological cell, tissue, organ, or organism, which are the end products of cellular processes. Messenger RNA (mRNA), gene expression data, and proteomic analyses reveal the set of gene products being produced in the cell, data that represents one aspect of cellular function. Conversely, metabolic profiling can give an instantaneous snapshot of the physiology of that cell, and thus, metabolomics provides a direct "functional readout of the physiological state" of an organism. There are indeed quantifiable correlations between the metabolome and the other cellular ensembles (genome, transcriptome, proteome, and lipidome), which can be used to predict metabolite abundances in biological samples from, for example mRNA abundances. One of the ultimate challenges of systems biology is to integrate metabolomics with all other -omics information to provide a better understanding of cellular biology.
=== Industrial synthesis === Nicotinic acid was first synthesized in 1867 by oxidative degradation of nicotine with potassium chromate and sulfuric acid — this is the origin of the name. Nicotinic acid is prepared by hydrolysis of nicotinonitrile, which, as described above, is generated by oxidation of 3-picoline. Oxidation can be effected by air, but ammoxidation is more efficient. In the latter process, nicotinonitrile is produced by ammoxidation of 3-methylpyridine. Nitrile hydratase is then used to catalyze nicotinonitrile to nicotinamide, which can be sold directly or converted to nicotinic acid. Alternatively, ammonia, acetic acid and paraldehyde are used to make 5-ethyl-2-methyl-pyridine, which is then oxidized to nicotinic acid. New "greener" catalysts are being tested using manganese-substituted aluminophosphates that use acetyl peroxyborate as non-corrosive oxidant, avoiding producing nitrogen oxides as do traditional ammoxidations. The demand for commercial production includes for animal feed and for food fortification meant for human consumption. According to Ullmann's Encyclopedia of Industrial Chemistry, worldwide 31,000 tons of nicotinamide were sold in 2014.
== Career == Upon receiving his Ph.D., Gattuso moved to Australia where he was a postdoctoral researcher at the Australian Institute of Marine Science(1988-1990). In 1990, Gattuso took a position of CNRS research scientist at Centre de Biologie et Écologie Tropicale et Méditerranéenne of the University of Perpignan (1990-1992). He then moved to the Scientific Center of Monaco to launch and lead the Ecophysiology and Biogeochemistry group. In 1998, Gattuso went back to a CNRS joint laboratory at the Villefranche Oceanographic Observatory and moved to the ranks of Research Professor (directeur de recherche). He is also Associate Scientist at the Institute for Sustainable Development and International Relations (IDDRI-SciencesPo, Paris). Gattuso has been visiting professor or scientist at Rutgers University, the National Center for Atmospheric Research and Shantou University. Gattuso is the founding editor-in-chief of Biogeosciences and served or has served in the editorial board of several scientific journals. He founded the Biogeosciences Division of the European Geosciences Union, and has received multiple awards and honors for his research contributions. He led the launch of the Ocean Acidification International Coordination Centre at the International Atomic Energy Agency, co-edited the first book on ocean acidification (Oxford University Press) and contributed to several IPCC products (5th Assessment Report, Special Report on 1.5°C of Warming, and the Special Report on the Ocean and Cryosphere in a Changing Climate).
JINR did not propose a name after their first report claiming synthesis of element 105, which would have been the usual practice. This led LBL to believe that JINR did not have enough experimental data to back their claim. After collecting more data, JINR proposed the name bohrium (Bo) in honor of the Danish nuclear physicist Niels Bohr, a founder of the theories of atomic structure and quantum theory; they soon changed their proposal to nielsbohrium (Ns) to avoid confusion with boron. Another proposed name was dubnium. When LBL first announced their synthesis of element 105, they proposed that the new element be named hahnium (Ha) after the German chemist Otto Hahn, the "father of nuclear chemistry", thus creating an element naming controversy. In the early 1970s, both teams reported synthesis of the next element, element 106, but did not suggest names. JINR suggested establishing an international committee to clarify the discovery criteria. This proposal was accepted in 1974 and a neutral joint group formed. Neither team showed interest in resolving the conflict through a third party, so the leading scientists of LBL—Albert Ghiorso and Glenn Seaborg—traveled to Dubna in 1975 and met with the leading scientists of JINR—Georgy Flerov, Yuri Oganessian, and others—to try to resolve the conflict internally and render the neutral joint group unnecessary; after two hours of discussions, this failed. The joint neutral group never assembled to assess the claims, and the conflict remained unresolved.
Sources: en.wikipedia.org
The consulting surgeon on the repeat surgery may not inform the first surgeon of the recurrence. The time it takes for a recurrent tumor to be visible to the patient might be 5 or more years. Quoted "cure" rates must be looked upon with the understanding that a 5-year cure rate might not necessarily be correct. As basal-cell carcinoma is a very slowly progressing tumor, a 5-year no recurrence rate might not be adequate. A longer follow-up might be needed to detect a slow-growing tumor left in the surgical scar. Poor training of the surgeon/pathologist/histotechnologist. While Mohs surgery is essentially a technical method of tissue handling and processing, the skill and training of the surgeon can greatly affect the outcome. Success requires a foundation of good tissue handling, good surgical skill, and hemostasis, based on the tissue processing and staining technique. A surgeon without a good histotechnologist does not have access to sufficiently high-quality information about the cancer, and a histotechnologist without a good surgeon can not produce quality slides. Originally, surgeons learned the procedure by spending a few hours to several months with Mohs or during their residencies. Today, many Mohs surgeons complete a fellowship after their dermatology residency, spending hundreds of hours observing and performing Mohs surgery under the careful supervision of highly experienced Mohs surgeons. This is the most comprehensive and thorough method of learning Mohs surgery. Others learn the technique in their dermatology residencies and through courses and preceptorships.
== Awards == On 29 September 2014, President Goodluck Jonathan honoured Muhammad with the national award of the Officer of the Order of the Niger (OON) for his contributions to primary health care in Nigeria. In 2013, Muhammad won the Public Administrator of the Year Award (PAYA), organized annually by the Centre for Policy Development and Political Studies, Lagos, Nigeria. The centre said after announcing the winner that of the 10 nominees for the award, Muhammad scored 3,025 votes, representing over 50 percent of the total votes cast. He was praised for his efforts in "eradication of poliomyelitis; reduction in maternal and infant mortality; initiatives in addressing human resource challenges in the primary health care sub-sector; integration and decentralization of HIV/AIDs intervention in PHC services in over 1,500 PHC facilities." Muhammad also won the Kwame Nkrumah Leadership Award and the Africa Leadership Icon in 2014 at the 71st Conference of AASU, held at OATTU Conference Centre, in Accra, Ghana. The Kwame Nkrumah Leadership Award and Africa Leadership Icon 2014 are awarded by the All-Africa Students' Union (AASU).
On July 9, Trump reversed a previously suspended military aid package to Ukraine following Russia's largest aerial assault on the country, involving hundreds of drones and missiles. The suspension, reportedly authorized by senior defense officials without Trump's prior knowledge. Trump expressed growing frustration with Russian president Vladimir Putin, accusing him of insincerity and relentless aggression, saying, "He wants to go all the way, just keep killing people, it's no good." The U.S. are discussing sending 10 Patriot missiles to Ukraine, and Trump said he is reviewing a proposed sanctions bill by Senator Lindsey Graham that would impose 500% tariffs on countries trading with Russia. Although Trump has previously mentioned secondary sanctions, none have been implemented so far, with the president citing their cost and waiting to see if a peace deal would emerge. On July 14, 2025, Trump threatened to impose 100% tariffs and secondary sanctions on countries purchasing Russian oil if Russia did not agree to a ceasefire within 50 days. Trump confirmed a summit meeting between him and Putin to be held on August 15, 2025, in Alaska The high-level summit at Joint Base Elmendorf–Richardson in Anchorage concluded without progress toward a ceasefire. Following the talks, Trump suggested the United States could assist Ukraine with surveillance flights or air defense support, while ruling out the deployment of ground troops.
Sources: en.wikipedia.org
It is a short synthetic peptide built from seven amino acids: methionine, glutamic acid, histidine, phenylalanine and three prolines. The sequence derives from the 4-10 fragment of adrenocorticotropic hormone with an added proline-glycine-proline tail. No plant or animal extract is involved; the material is produced by solid-phase peptide synthesis.
It was developed in the Soviet Union during the early 1980s by groups at the Institute of Molecular Genetics in Moscow. Russian approval for intranasal use followed, and it has been marketed there since. Western laboratories encountered it mainly through translated literature and, later, through online research-chemical trade.
It holds a Russian registration as a prescription nasal product but has no approval from the European Medicines Agency or the United States Food and Drug Administration. Buyers outside Russia usually receive material sold strictly for laboratory research. That distinction matters because research-grade and pharmaceutical-grade products carry different documentation and testing expectations.
The main proposal is modulation of neurotrophic factors such as brain-derived neurotrophic factor, supported largely by animal experiments. Receptor-level targets have not been firmly established. Most reviews describe the mechanism as only partially characterized.