Diverse mechanisms of bioproduction heterogeneity in fermentation and their control strategies.

Microbial bioproduction often faces challenges related to populational heterogeneity, where cells exhibit varying biosynthesis capabilities. Bioproduction heterogeneity can stem from genetic and non-genetic factors, resulting in decreased titer, yield, stability, and reproducibility. Consequently, understanding and controlling bioproduction heterogeneity are crucial for enhancing the economic competitiveness of large-scale biomanufacturing. In this review, we provide a comprehensive overview of current understandings of the various mechanisms underlying bioproduction heterogeneity. Additionally, we examine common strategies for controlling bioproduction heterogeneity based on these mechanisms. By implementing more robust measures to mitigate heterogeneity, we anticipate substantial enhancements in the scalability and stability of bioproduction processes. ONE-SENTENCE SUMMARY: This review summarizes current understandings of different mechanisms of bioproduction heterogeneity and common control strategies based on these mechanisms.

Dissecting LuxS/AI-2 quorum sensing system-mediated phenyllactic acid production mechanisms of Lactiplantibacillus plantarum L3.

The phenyllactic acid (PLA) produced by lactic acid bacteria (LAB) inhibits fungi and facilitates the quality control of fermented milk. A strain of Lactiplantibacillus plantarum L3 (L. plantarum L3) with high PLA production was screened in the pre-laboratory, but the mechanism of its PLA formation is unclear. The amount of autoinducer-2 (AI-2) increased with increasing culture time, as did cell density and PLA. The results in this study suggest that PLA production in L. plantarum L3 may be regulated by the LuxS/AI-2 Quorum Sensing (QS) system. Tandem mass tag (TMT) quantitative proteomics analysis showed that a total of 1291 differentially expressed proteins (DEPs) were quantified in the incubated for 24 h compared with the incubated for 2 h, of which 516 DEPs were up-regulated and 775 DEPs were down-regulated. Among them, S-ribosomal homocysteine lyase (luxS), aminotransferase (araT), and lactate dehydrogenase (ldh) are the key proteins for PLA formation. The DEPs were mainly involved in the QS pathway and the core pathway of PLA synthesis. Furanone effectively inhibited the production of L. plantarum L3 PLA. In addition, Western blot analysis demonstrated that luxS, araT, and ldh were the key proteins regulating PLA production. This study reveals the regulatory mechanism of PLA based on the LuxS/AI-2 QS system, which provides a theoretical basis for the efficient and large-scale production of PLA in industries in the future.

Recent Progress in the Development of Fluorescent Probes for the Detection of Hydrazine (N2H4).

ABSTACTWith the widespread use of N2H4, it brings potential risk to human health and environmental safety because of its diverse toxicological functions. In order to determine N2H4 effectively in both environment and living systems, all kinds of fluorescence probes have been prepared for the specific response of N2H4 based on various mechanisms and different acceptor group for N2H4. This paper provides a review to bring more inspirations for the development of the fluorescent probes for N2H4.

Nasal-type extranodal natural killer/T-cell lymphoma with oral ulcer as the earliest clinical manifestation.

Nasal-type extranodal natural killer/T-cell lymphoma (ENKTL-NT) is a special subtype of non-Hodgkin's lymphoma derived from natural killer cells or cytotoxic T cells. Oral ulcers as the first symptom makes its diagnosis challenging because of its rarity and lack of understanding. We report a case of ENKTL-NT in this paper. We analyzed the clinicopathological features, differential diagnosis, treatment, prognosis and the causes of misdiagnosis to provide a diagnostic basis for dentists to make better clinical diagnosis and treatment.

Microbial production of megadalton titin yields fibers with advantageous mechanical properties.

Manmade high-performance polymers are typically non-biodegradable and derived from petroleum feedstock through energy intensive processes involving toxic solvents and byproducts. While engineered microbes have been used for renewable production of many small molecules, direct microbial synthesis of high-performance polymeric materials remains a major challenge. Here we engineer microbial production of megadalton muscle titin polymers yielding high-performance fibers that not only recapture highly desirable properties of natural titin (i.e., high damping capacity and mechanical recovery) but also exhibit high strength, toughness, and damping energy - outperforming many synthetic and natural polymers. Structural analyses and molecular modeling suggest these properties derive from unique inter-chain crystallization of folded immunoglobulin-like domains that resists inter-chain slippage while permitting intra-chain unfolding. These fibers have potential applications in areas from biomedicine to textiles, and the developed approach, coupled with the structure-function insights, promises to accelerate further innovation in microbial production of high-performance materials.

A cationic fluorescent probe for highly selective detection of sodium dodecyl sulfate (SDS) by electrostatic and hydrophobic self-assembly.

Sodium dodecyl sulfate (SDS) has a wide range of applications in the chemical industry due to its excellent characteristics including good emulsification, foaming, water solubility and stability, easy synthesis and low price. However, it is a kind of anionic surfactant which is slightly toxic to the human body, and use of a large amount will cause potential pollution of the environment. Therefore, the development of a simple method to realize the monitoring of SDS in the environment is of great significance. Herein, a cationic fluorescent probe was prepared by the condensation reaction between 4-di-p-tolylamino-benzaldehyde and 3-ethylbenzothiazolium iodide. It can be used for the quantitative determination of SDS in the range of 5-50 µM showing red fluorescence and high selectivity by forming banded assemblies. This work provides an effective tool based on a new strategy for the detection of SDS.

A 2-Hydroxy-1-naphthaldehyde Schiff Base for Turn-on Fluorescence Detection of Zn2+ Based on PET Mechanism.

Zinc ion is closely related to human health. Its content in human body is small, while the effect is large. However, it is not the more the better, must be in a scientific balance. Therefore, it is significant to the rapid detection of Zn2+ in the environment and organism. Herein, a fluorescent probe based on 2-hydroxy-1-naphthalene formaldehyde and furan-2-carbohydrazide was conveniently synthesized via Schiff base reaction. And this probe has been successfully applied to the accurate and quantitative detection of Zn2+ in real samples, showing turn on fluorescence, good selectivity, very low detection limit, real time response and reusability. In addition, this probe has the potential application to trace Zn2+ in living cells with low cytotoxicity.

A reusable test paper based on a simple salicylaldehyde derivate for the real-time detection of phosgene in gas phase.

Phosgene is an important organic activity intermediate as well as a poisonous gas. However, the widespread use and abuse of phosphene brings potential risks to public safety. So it is very important to detect phosgene quickly and reliably. Up to now, a lot of chemical sensors based on organoluminescent groups have been reported to monitor phosgene. However, most of them have complex molecular structures and cannot be recycled during detection. Herein, we developed a simple and effective fluorescent chemosensor using 5-chlorsalicylaldehyde as luminophor and azanol as recognition site. It exhibited significant fluorescence enhancement, excellent specificity and sensitivity. More importantly, the reusable test paper prepared by this chemosensor has been successfully used in the point-of-care testing of gaseous phosgene.

A Fluorescent Probe for the Fast Detection of Hypochlorite and its Applications in Water, Test Strip and Living Cells.

Hypochlorite (ClO-) mediated by oxidative stress play an important role in the body's defense system due to their physiological and pathological significance. In this work, a new and simple probe was designed and synthesized to detect hypochlorite. This probe could rapidly respond to hypochlorite in a short time (20 s) in aqueous media, and showed excellent selectivity and sensitivity, and a wide pH range of 3 ̶ 12, as well as the low detection limit of 1.44 nM. In addition, it was successfully applied to the detection of ClO- in water sample, test paper experiment, and cell imaging.

A ratiometric fluorescent probe for the rapid and specific detection of HSO3 - in water samples.

Hydrosulphite (HSO3 - ), as a common and important chemical reagent, is widely used in everyday life, however excessive use and abuse of HSO3 - can cause potential harmful effects on the environment and in biological health. In this paper, we describe the design and preparation of a colorimetric and ratiometric fluorescence probe for the visual detection of HSO3 - (excitation wavelengths were, respectively, 336 nm and 520 nm). This method showed some advantages including simple preparation, high selectivity, fast response, and significant colour and fluorescence ratio (F450 /F594 ) changes in the presence of HSO3 - . In addition, this probe was used successfully for the detection of HSO3 - in real water samples and showed a good recovery rate range.

A metal-free coumarin-based fluorescent probe for the turn-on monitoring of carbon monoxide in an aqueous solution and living cells.

Endogenous carbon monoxide (CO) is an essential cell signaling molecule, which is closely related to numerous physiological and pathological processes. Therefore, it is of great significance to monitor CO in living samples. Fluorescent probe technique provides an effective and convenient method for monitoring CO. Although many fluorescent probes of CO have been reported, most of them require the introduction of heavy metal ions (Pd2+), which is not conducive to the practical application of these probes. Herein, a metal-free coumarin-based fluorescent probe was developed for monitoring CO. For this probe, coumarin was selected as the fluorophore, the aromatic nitro group was used as the reactive site, and the carboxyl moiety acted as the water-soluble unit. As a result, this probe has been proved to be able to monitor CO with good specificity and excellent sensitivity in water medium. After interacting with CO, the aromatic group was reduced to an aryl amino group; accordingly, the emission intensity of the peak corresponding to the probe at 450 nm significantly increased. Moreover, it successfully realized the detection of CO in living cells by a fluorescence signal.

Role of organic components in regulating denitrification in the coastal water of Daya Bay, southern China.

Both dissolved and particulate organic materials have been proposed to be important factors in regulating heterotrophic denitrification in various aquatic environments. However, the specific pathways and mechanisms remain elusive. In this study, water column samples were collected from Daya Bay, southern China, to examine the relationships between potential denitrification and different organic components in the water column. Bulk dissolved organic carbon (DOC) was categorized into three major components including terrigenous fluorescent (tFDOC), autochthonous fluorescent (bFDOC) and non-fluorescent (nFDOC) fractions, while the bulk particulate organic carbon (POC) was divided into terrigenous (tPOC) and autochthonous (bPOC) fractions based on an isotope mixing model. Potential denitrification derived from in situ incubation experiments under anoxic conditions was evident (ranging from 6 to 107 nmol N2 per L per h) and varied markedly among stations. When normalized to nitrate concentration, the denitrification rate (NDR) followed a positive trend with either the concentration or proportion of tFDOC, and a negative trend with the proportion of nFDOC, suggesting tFDOC was potentially favorable while nFDOC was unfavorable for denitrifying degradation. In comparison, the NDR showed a significant positive correlation with the proportion of bPOC in the bulk POC (p = 0.01), with a predictive power of >70%, indicating that the composition of POC has a substantial impact on potential denitrification. Furthermore, if both bPOC and suspended particulate matter (SPM) were considered as variables concurrently, the variability of NDR can be better predicted with a predictive power as high as 80%. Therefore, denitrifiers may preferentially utilize fresher and labile autochthonous POC instead of DOC especially in coastal waters where particles/colloids are abundant. Our results thus provide new insights for a better understanding of denitrification mechanisms in water columns and the importance of both suspended particles and POC components in regulating denitrification, especially in turbid and productive coastal environments.