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Abstract Background Rhegmatogenous retinal detachment (RRD) is a serious condition that occurs when the retina detaches from its underlying retinal pigment epithelium. RRDs associated with giant retinal tears (GRTs) are caused by retinal tears at least 90° or one-quarter of the circumferential extent. This scoping review systematically identifies and summarizes clinical studies evaluating surgical techniques for the management of GRT-related RRDs, discusses functional and visual outcomes and the risk factors affecting treatment outcomes. Methods This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, Google Scholar, and Springer Link databases were searched for relevant papers (from January 2001 to March 2023). Studies that were published in the English language and reported the risk factors, management, and treatment outcomes of GRT-related RRDs were included in the review. The outcome measures included anatomic success rates, changes in BCVA (logMAR) from baseline to the final follow-up, and adverse events. Results A total of 11,982 articles were identified. After the title and abstract review, 71 studies were deemed eligible for full-text review. Thirty-six studies that met the eligibility criteria were included in the final review. Four surgical techniques were identified: pars plana vitrectomy (PPV), combined PPV and scleral buckling, scleral buckling alone, and pneumatic retinopexy. Various types of tamponades, including gas, silicone oil, and air, have been used. PPV was the most commonly used surgical technique in 33.1–100% of patients. Among the 20 studies that used PPV alone, 17 were associated with preoperative PVR. In addition, scleral buckling alone or in combination with PPV was reported as a treatment option in 10 studies, with 2–100% of patients experiencing scleral buckling alone and 13.6–100% experiencing combined PPV and complementary scleral buckling. Primary anatomic success (PAS) was achieved with retinal reattachment via a single operation with no residual tamponade, whereas final anatomic success (FAS) was achieved via more than one operation with no residual tamponade. Reported single surgery anatomic success (SSAS) rates range from 65.51 to 100%. The preoperative best-corrected visual acuity (BCVA) ranged from 0.067 to 2.47 logMAR, whereas the postoperative BCVA ranged from 0.08 to 2.3 logMAR. An improvement in visual acuity was observed in 29 studies. Cataracts (3.9-28.3%) were the most common postoperative complication, followed by high IOP (0.01-51.2%) and PVR (0.8-31.57%). Conclusion PPV is the most common surgical technique, and currently microincision vitrectomy surgery (MIVS) systems are commonly employed. Silicone oil is the most frequently used tamponade in RRD repair. Risk factors for GRT-related RRD include age, sex, lens status, high myopia status, proliferative vitreoretinopathy (PVR), presenting visual acuity, the extent of the GRT and retinal detachment, and macular involvement. Future research areas include guidelines to reduce variability in the reporting of surgical methodology, choice of tamponades, and reporting of functional and visual outcomes to inform the best therapeutic interventions in GRT-related RRD.

The current petroleum chemical methods for fumaric acid production can cause heavy pollution and global warming. In this study, the engineered strains of A. pullulans var. aubasidani were found to be suitable for green fumaric acid producer. Removal and complementation of the relevant genes showed only the ornithine-urea cycle (OUC) was involved in high level fumarate biosynthesis which was controlled by the Ca2+ signaling pathway. Removal of both the GOX gene encoding glucose oxidase and the PKS1 gene encoding the polyketide synthase for 3,5-dihydroxydecanoic acid biosynthesis and overexpression of the PYC gene encoding pyruvate carboxylase made the strain e-PYC produce 88.1 ± 4.3 g/L of fumarate at flask level and 93.9 ± 0.8 g/L of fumarate during the fed-batch fermentation. As a yeast-like fungal strain, it was very easy to cultivate A. pullulans var. aubasidani DH177 and their mutants in the bioreactor and to edit its genomic DNAs to enhance fumarate production. It was found that 2 mol of CO2 could be fixed during a maximal theoretical yield of 2 mol of fumarate per mole of glucose consumed in the OUC. Therefore, the OUC-mediated fumarate biosynthesis pathway in A. pullulans var. aubasidani was a green and eco-friendly process for the global sustainable development and carbon neutrality.

Abstract Background Lignocellulose is a valuable carbon source for the production of biofuels and biochemicals, thus having the potential to substitute fossil resources. Consolidated bio-saccharification (CBS) is a whole-cell-based catalytic technology previously developed to produce fermentable sugars from lignocellulosic agricultural wastes. The deep-sea yeast strain Rhodotorula paludigena P4R5 can produce extracellular polyol esters of fatty acids (PEFA) and intracellular single-cell oils (SCO) simultaneously. Therefore, the integration of CBS and P4R5 fermentation processes would achieve high-value-added conversion of lignocellulosic biomass. Results The strain P4R5 could co-utilize glucose and xylose, the main monosaccharides from lignocellulose, and also use fructose and arabinose for PEFA and SCO production at high levels. By regulating the sugar metabolism pathways for different monosaccharides, the strain could produce PEFA with a single type of polyol head. The potential use of PEFA as functional micelles was also determined. Most importantly, when sugar-rich CBS hydrolysates derived from corn stover or corncob residues were used to replace grain-derived pure sugars for P4R5 fermentation, similar PEFA and SCO productions were obtained, indicating the robust conversion of non-food corn plant wastes to high-value-added glycolipids and lipids. Since the produced PEFA could be easily collected from the culture via short-time standing, we further developed a semi-continuous process for PEFA production from corncob residue-derived CBS hydrolysate, and the PEFA titer and productivity were enhanced up to 41.1 g/L and 8.22 g/L/day, respectively. Conclusions Here, we integrated the CBS process and the P4R5 fermentation for the robust production of high-value-added PEFA and SCO from non-food corn plant wastes. Therefore, this study suggests a feasible way for lignocellulosic agro-waste utilization and the potential application of P4R5 in industrial PEFA production.

ABSTRACT Chemotaxis is an important virulence factor in some enteric pathogens, and it is involved in the pathogenesis and colonization of the host. However, there is limited knowledge regarding the environmental signals that promote chemotactic behavior and the sensing of these signals by chemoreceptors. To date, there is no information on the ligand molecule that directly binds to and is sensed by Campylobacter jejuni Tlp1, which is a chemoreceptor with a dCache-type ligand-binding domain (LBD). dCache (double Calcium channels and chemotaxis receptor) is the largest group of sensory domains in bacteria, but the dCache-type chemoreceptor that directly binds to formate has not yet been discovered. In this study, formate was identified as a direct-binding ligand of C. jejuni Tlp1 with high sensing specificity. We used the strategy of constructing a functional hybrid receptor of C. jejuni Tlp1 and the Escherichia coli chemoreceptor Tar to screen for the potential ligand of Tlp1, with the binding of formate to Tlp1-LBD being verified using isothermal titration calorimetry. Molecular docking and experimental analyses indicated that formate binds to the membrane-proximal pocket of the dCache subdomain. Chemotaxis assays demonstrated that formate elicits robust attractant responses of the C. jejuni strain NCTC 11168, specifically via Tlp1. The chemoattraction effect of formate via Tlp1 promoted the growth of C. jejuni, especially when competing with Tlp1- or CheY-knockout strains. Our study reveals the molecular mechanisms by which C. jejuni mediates chemotaxis toward formate, and, to our knowledge, is the first report on the high-specificity binding of the dCache-type chemoreceptor to formate as well as the physiological role of chemotaxis toward formate. IMPORTANCE Chemotaxis is important for Campylobacter jejuni to colonize favorable niches in the gastrointestinal tract of its host. However, there is still a lack of knowledge about the ligand molecules for C. jejuni chemoreceptors. The dCache-type chemoreceptor, namely, Tlp1, is the most conserved chemoreceptor in C. jejuni strains; however, the direct-binding ligand(s) triggering chemotaxis has not yet been discovered. In the present study, we found that the ligand that binds directly to Tlp1-LBD with high specificity is formate. C. jejuni exhibits robust chemoattraction toward formate, primarily via Tlp1. Tlp1 is the first reported dCache-type chemoreceptor that specifically binds formate and triggers strong chemotaxis. We further demonstrated that the formate-mediated promotion of C. jejuni growth is correlated with Tlp1-mediated chemotaxis toward formate. Our work provides important insights into the mechanism and physiological function of chemotaxis toward formate and will facilitate further investigations into the involvement of microbial chemotaxis in pathogen-host interactions.

M. bicuspidata var. bicuspidata is a pathogenic yeast which can affect aquacultured and marine-cultured animals such as brine shrimp, ridgetail white prawn, chinook salmon, giant freshwater prawn, the Chinese mitten crab, marine crab, the mud crab, the mangrove land crab, the Chinese grass shrimp, sea urchins, sea urchins, Daphnia dentifera and even snails, causing a milky disease, and it has caused big economic losses in aquacultural and marine-cultural industries in the past. However, the detailed mechanisms and the reasons for the milky disease in the diseased aquatic animals are still completely unknown. So far, only some antimycotics, killer toxins and Massoia lactone haven been found to be able to actively control and kill its growth. The ecofriendly, green and renewable killer toxins and Massoia lactone have high potential for application in controlling the milky disease.

BackgroundShort-acting β2-agonists (SABA), the most potent and rapid-acting relievers are commonly used to provide quick relief of asthma symptoms. However, there is an increasing concern regarding the misuse of SABA medicines.ObjectiveThis qualitative systematic review aims to determine, evaluate, and summarize the perceptions, attitudes, and behaviors towards the use of SABA from the patients' perspectives.MethodsThe databases searched included PubMed, Scopus, PsycINFO, CINAHL, and Cochrane database. Original research articles reporting the perceptions, attitudes, or behaviors of asthma patients towards the use of SABA, which was available as full text, published in the English language between the year 2000 and February 2023 were included in the review. Commentaries, letters to editor, review articles, and conference proceedings were excluded.ResultsA total of five articles were included. Six overarching themes were obtained: (1) perceptions on health status; (2) perceptions and attitudes towards the impact of asthma; (3) perceptions towards asthma control; (4) perceptions towards asthma knowledge; (5) risk perceptions; (6) perceptions, attitudes, and behaviors towards the use of SABA.ConclusionDespite the fact that SABA could rapidly alleviate asthma symptoms, SABA over-users were less likely to describe their health status and asthma control as 'excellent'. Most SABA over-users did not know that frequent SABA usage would worsen their asthma control, and they exhibited psychological linkage towards the use of SABA. Collaborative efforts between policymakers, healthcare professionals and patients are warranted to reconstruct SABA prescribing practice and usage.

Summary Currently, piperazic acid is chemically synthesized using ecologically unfriendly processes. Microbial synthesis from glucose is an attractive alternative to chemical synthesis. In this study, we report the production of L‐piperazic acid via microbial fermentation with the first engineered fungal strain of Aureobasidium melanogenum; this strain was constructed by chassis development, genetic element reconstitution and optimization, synthetic rewiring and constitutive genetic circuit reconstitution, to build a robust L‐piperazic acid synthetic cascade. These genetic modifications enable A. melanogenum to directly convert glucose to L‐piperazic acid without relying on the use of either chemically synthesized precursors or harsh conditions. This bio‐based process overcomes the shortcomings of the conventional synthesis routes. The ultimately engineered strain is a very high‐efficient cell factory that can excrete 1.12 ± 0.05 g l‐1 of L‐piperazic acid after a 120‐h 10.0‐l fed‐batch fermentation; this is the highest titre of L‐piperazic acid reported using a microbial cell factory.

TcpC is a well characterised multifunctional virulence factor expressed by uropathogenic Eschericia coli. Here the authors show that TcpC also targets neutrophil NETosis via its E3 ligase functionality promoting the degradation of PAD4, and represents an additional immune evasion function of this bacterially derived virulence factor.

The exploitation of carbon dots (CDs) is now flourishing; however, more effort is needed to overcome their lack of intrinsic specificity. Herein, instead of synthesizing novel CDs, we reinvestigated three reported CDs and discovered that plain ammonium citrate CDs (AC-CDs) exhibited surprising specificity for Helicobacter pylori. Notably, we showed that the interfacial mechanism behind this specificity was due to the affinity between the high abundant urea/ammonium transporters on H. pylori outer membrane and the surface-coordinated ammonium ions on AC-CDs. Further, we justified that ammonium sulfate-citric acid CDs also possessed H. pylori-specificity owing to their NH4+ doping. Thereby, we suggested that the incorporation of a molecule that could be actively transported by abundant membrane receptors into the precursors of CDs might serve as a basis for developing a plain CD with intrinsic specificity for H. pylori. Moreover, AC-CDs exhibited specificity towards live, dead, and multidrug-resistant H. pylori strains. Based on the specificity, we developed a microfluidics-assisted in vitro sensing approach for H. pylori, achieving a simplified, rapid and ultrasensitive detection with two procedures, shortened time within 45.0 ​min and a low actual limit of detection of 10.0 ​CFU ​mL−1. This work sheds light on the design of more H. pylori-specific or even bacteria-specific CDs and their realistic translation into clinical practice.

Zinc oxide nanoparticles (ZnO NPs) have been widely used in biomedical applications due to their high biocompatibility and low toxicity to humans. The present work aimed to investigate the antibacterial effects of different concentrations of ZnO NPs on two opportunistic pathogens, Serratia marcescens and Enterococcus faecalis. The surface interaction between nanoparticles and bacterial cell wall, and the subsequent morphological alterations on the bacterial surface, were examined through Fourier transform infrared spectroscopy and scanning electron microscope. The energy dispersive X-ray analysis was used to confirm the elemental composition of ZnO NPs and the cellular accumulation of ZnO NPs in bacteria. The growth-inhibitory test demonstrated a dose-dependent growth inhibitory effect of ZnO NPs against both the test bacteria, as the higher concentration of nanoparticles caused the higher bacterial growth inhibition. The results showed that ZnO NPs caused a higher growth inhibition (63.50 ± 2.50%) on the Gram-positive bacterium E. faecalis compared to the Gram-negative bacterium S. marcescens (51.27 ± 4.56%). Fourier transform infrared spectrum revealed the possible involvement of hydroxyl, carboxyl, amides, methylene, and phosphate groups from the biomolecules of bacterial cell wall such as proteins, carbohydrates, lipids, and phospholipids in the interaction of ZnO NPs on bacterial cell surface. Energy dispersive X-ray analysis showed the higher accumulation of ZnO NPs in E. faecalis than S. marcescens analogous to the bacterial growth inhibition. Scanning electron microscopy images confirmed the antibacterial properties of ZnO NPs, showing the loss of integrity of cell membrane and distortion of bacterial cells. Hence, the potential of ZnO NP as an antibacterial agent against S. marcescens and E. faecalis has been confirmed.

This work investigated the effects of the bioflavonoid hesperetin-7-rhamnoglucoside isolated from Citrus uranium fruit peel on Helicobacter pylori (H. pylori). Separation and purity, crystalline state, and urease inhibition assays were carried out. Then, molecular docking and molecular dynamics (MD) simulations were conducted with urease as the target protein. Hesp was isolated from citrus peel with a purity of 95.14 µg mg−1 of dry raw material. X-ray diffraction analysis, hydrogen-1 nuclear magnetic resonance, Fourier transform infrared spectroscopy, and differential scanning calorimetry revealed that pure Hesp had the same crystallinity rating as the Hesp standard. The kinetic inhibition study demonstrated that Hesp inhibited H. pylori urease in a competitive and concentration-dependent manner with jack bean urease. In addition, bioimaging studies with laser scanning confocal microscopy and scanning electron microscopy illustrated that Hesp interacted with bacterial cells and induced membrane disruption by creating holes in the outer membranes of the bacterial cells, resulting in the leakage of amino acids. Importantly, molecular docking and 20 ns MD simulations revealed that Hesp inhibited the target protein through slow-binding inhibition and hydrogen bond interactions with active site residues, namely, Gly11 (O⋯H distance = 2.2 Å), Gly13 (O⋯H distance = 2.4 Å), Ser12 (O⋯H distance = 3.3 Å), Lys14 (O⋯H distance = 3.3 Å), and Arg179 (O⋯H distance = 2.7 Å). This work presents novel anti- H. pylori agents from natural sources.

Abstract Background Polyol esters of fatty acids (PEFA) are a kind of promising biosurfactants and mainly secreted by Rhodotorula strains. In addition, some strains of Rhodotorula are reliable producers of microbial lipid. Therefore, it is feasible to establish a one step fermentation process for efficient simultaneous production of PEFA and microbial lipids by a suitable Rhodotorula strain. Results A newly isolated deep-sea yeast, Rhodotorula paludigena P4R5, was shown to simultaneously produce high level of intracellular lipid and extracellular PEFA. Under the optimized conditions, it could yield 48.5 g/L of PEFA and 16.9 g/L of intracellular lipid within 156 h from inulin during 10-L batch fermentation. The PEFA consisting of a mixture of mannitol esters of 3-hydroxy C14, C16 and C18 fatty acids with variable acetylation showed outstanding surface activity and emulsifying activity, while the fatty acids of the intracellular lipid were mainly C16 and C18 and could be high-quality feedstock for biodiesel production. Conclusion The deep-sea yeast strain R. paludigena P4R5 was an excellent candidate for efficient simultaneous of biosurfactants and biodiesel from inulin. Our results also suggested that the establishment of fermentation systems with multiple metabolites production was an effective approach to improve the profitability.

TcpC is a virulence factor of uropathogenic E. coli (UPEC). It was found that TIR domain of TcpC impedes TLR signaling by direct association with MyD88. It has been a long-standing question whether bacterial pathogens have evolved a mechanism to manipulate MyD88 degradation by ubiquitin-proteasome pathway. Here, we show that TcpC is a MyD88-targeted E3 ubiquitin ligase. Kidney macrophages from mice with pyelonephritis induced by TcpC-secreting UPEC showed significantly decreased MyD88 protein levels. Recombinant TcpC (rTcpC) dose-dependently inhibited protein but not mRNA levels of MyD88 in macrophages. Moreover, rTcpC significantly promoted MyD88 ubiquitination and accumulation in proteasomes in macrophages. Cys12 and Trp106 in TcpC are crucial amino acids in maintaining its E3 activity. Therefore, TcpC blocks TLR signaling pathway by degradation of MyD88 through ubiquitin-proteasome system. Our findings provide not only a novel biochemical mechanism underlying TcpC-medicated immune evasion, but also the first example that bacterial pathogens inhibit MyD88-mediated signaling pathway by virulence factors that function as E3 ubiquitin ligase.

Nanoemulsions (NEs) have been made for improving the delivery and disperse of bioactive compounds. In this study, it was found that the best ingredients for the stable Massoia lactone-loaded and food-grade NEs making were 560.0 µL of Tween-80, 240.0 µL of Span-80 and 200.0 µL of Massoia lactone. Then, 9.0 mL of distilled water was titrated into the mixture under continuous magnetic stirring (750 rotations min−1) with about 2 drops per second for 20 min. Finally, the system was treated by ultrasonication using an ultrasonic generator (180 W and 22 KHz) for 5 min. All the prepared particles with a mean droplet diameter of 43 nm were spherical, had uniform size distribution and were equally distributed in the Massoia lactone-loaded NEs. The obtained Massoia lactone-loaded nanoemulsions (NEs) were very stable without changes of the mean droplet diameter and polydispersity indexes (PDI) for over two months under different conditions. As with free Massoia lactone, Massoia lactone loaded in the NEs had high anti-fungal activity against Metschnikowia bicuspidate LIAO, a pathogenic yeast causing milky disease in the Chinese mitten crab by damaging its cell membrane and causing cellular necrosis. Massoia lactone loaded in the NEs also had the DPPH radical scavenging activity and the hydroxyl radical scavenging activity.

The yeast Saccharomyces cerevisiae has been widely applied in fermentation industries, chemical industries and biological research and it is widespread in different environments, especially in sugar-rich environments. However, little is known about the occurrence, distribution and roles of S. cerevisiae in marine environments. In this study, only 10 strains among all the yeasts isolated from different marine environments belonged to S. cerevisiae. It was found that most of the strains of S. cerevisiae in marine environments occurred in guts, the surface of marine fish and mangrove trees. In contrast, they were not found in seawater and sediments. All the strains of S. cerevisiae isolated from the marine environments had a lower ability to produce ethanol than the highly alcohol-producing yeast Saccharomyces sp. W0 isolated from fermented rice, but the strains 2E00400, 2E00558, 2E00498, 2E00723, 2E00724 could produce higher concentrations of ethanol than any other marine-derived strains of S. cerevisiae obtained in this study. However, some of them had higher ethanol tolerance and higher trehalose content than Saccharomyces sp. W0. In particular, ethanol tolerance of the yeast strain 2E00498 was higher than that of Saccharomyces sp. W0. This may be related to the harsh marine environments from which they were isolated. Such yeast strains with higher alcohol tolerance could be used to further improve the alcohol tolerance of Saccharomyces sp. W0.

Background: There remains significant debate as to the relationship between fragmented QRS (fQRS) complexes on electrocardiogram (ECG) and acute myocardial infarction (AMI). Few studies have reported on this relationship in non-ST elevated AMI (NSTEMI), and thus, we attempt to assess this relationship and its potential short-term prognostic value. Methods: This was a single-center, observational, retrospective cohort study. A total of 513 consecutive patients (399 men, 114 women) with NSTEMI within 24 h who underwent coronary angiography at our department, between January 1, 2014, and December 31, 2014. Patients were divided into 2 groups according to the presence or absence of fQRS complex on the admission ECG. fQRS complexes were defined as the existence of an additional R' or crochetage wave, notching in the nadir of the S wave, RS fragmentation, or QS complexes on 2 contiguous leads. All patients were followed up for 6 months, and all major adverse cardiac events (MACE) were recorded. Results: In this study, there were 285 patients with fQRS ECG in the 513 patients with NSTEMI. The number of patients with 0–2 coronary arteries narrowed by ≥50% in fQRS group were less while patients with 3 narrowed arteries were more than in the non-fQRS group (P = 0.042). There were fewer Killip Class I patients in the fQRS group (P = 0.019), while Killip Class II, III, and IV patients were more in the fQRS group than in the non-fQRS group (P = 0.019). Left ventricular ejection fraction levels were significantly lower in the fQRS group (P = 0.021). Baseline total cholesterol, low-density lipoprotein, creatinine, creatine kinase, homocysteine, high-sensitivity C-reactive protein (CRP), and red blood cells distribution width levels were significantly higher in the fQRS group. Total MACE (MACE, P = 0.028), revascularization (P = 0.005), and recurrent angina (P = 0.005) were also significantly greater in the fQRS group. On final logistic regression analysis, after adjusting for baseline variables, the following variables were independent predictors of fQRS: Coronary artery narrowing (P = 0.035), Killip classification (P = 0.026), and total cholesterol (P = 0.002). The following variables were found to be independent predictors of preoperative MACE: Hemoglobin (P = 0.000), gender (P = 0.026), fQRS (P = 0.016), and time from myocardial infarction to balloon or coronary artery bypasses grafting (P = 0.013). Conclusions: The fQRS complexes are commonly present in NSTEMI and the fQRS complexes are an independent predictor of MACE in NSTEMI patients. The number of narrowed coronary arteries, Killip classification, and total cholesterol are all independent predictors of the fQRS complexes.

Chinese white wax solid lipid nanoparticles (cwSLNs) were prepared by high shear homogenization and ultrasound methods. Using an optimized formula, spherical cwSLNs with an average particle size of 401.9 ± 21.3 nm were obtained. The cwSLNs showed high entrapment efficiency, approximately 84.6%, for loading curcumin. The curcumin loaded cwSLNs (Cur-cwSLNs) exhibited sustained drug release properties. Notably, Cur-cwSLNs had a higher drug release rate at pH 4.5 than at pH 7.4, which suggested their applicability in an acidic environment. Cur-cwSLNs were able to inhibit the growth of Staphylococcus aureus and were more effective at reducing the biofilms produced by this bacterium compared to free curcumin. This study confirmed that cwSLNs may be novel carriers for increasing the bioavailability of curcumin with the potential to inhibit the formation of S. aureus biofilms.