Single-cell transcriptomic profiling of the mouse cochlea: An atlas for targeted therapies.

Functional molecular characterization of the cochlea has mainly been driven by the deciphering of the genetic architecture of sensorineural deafness. As a result, the search for curative treatments, which are sorely lacking in the hearing field, has become a potentially achievable objective, particularly via cochlear gene and cell therapies. To this end, a complete inventory of cochlear cell types, with an in-depth characterization of their gene expression profiles right up to their final differentiation, is indispensable. We therefore generated a single-cell transcriptomic atlas of the mouse cochlea based on an analysis of more than 120,000 cells on postnatal day 8 (P8), during the prehearing period, P12, corresponding to hearing onset, and P20, when cochlear maturation is almost complete. By combining whole-cell and nuclear transcript analyses with extensive in situ RNA hybridization assays, we characterized the transcriptomic signatures covering nearly all cochlear cell types and developed cell type-specific markers. Three cell types were discovered; two of them contribute to the modiolus which houses the primary auditory neurons and blood vessels, and the third one consists in cells lining the scala vestibuli. The results also shed light on the molecular basis of the tonotopic gradient of the biophysical characteristics of the basilar membrane that critically underlies cochlear passive sound frequency analysis. Finally, overlooked expression of deafness genes in several cochlear cell types was also unveiled. This atlas paves the way for the deciphering of the gene regulatory networks controlling cochlear cell differentiation and maturation, essential for the development of effective targeted treatments.

In situ spectroelectrochemical probing of CO redox landscape on copper single-crystal surfaces.

Electrochemical reduction of CO(2) to value-added chemicals and fuels is a promising strategy to sustain pressing renewable energy demands and to address climate change issues. Direct observation of reaction intermediates during the CO(2) reduction reaction will contribute to mechanistic understandings and thus promote the design of catalysts with the desired activity, selectivity, and stability. Herein, we combined in situ electrochemical shell-isolated nanoparticle-enhanced Raman spectroscopy and ab initio molecular dynamics calculations to investigate the CORR process on Cu single-crystal surfaces in various electrolytes. Competing redox pathways and coexistent intermediates of CO adsorption (*COatop and *CObridge), dimerization (protonated dimer *HOCCOH and its dehydrated *CCO), oxidation (*CO2- and *CO32-), and hydrogenation (*CHO), as well as Cu-Oad/Cu-OHad species at Cu-electrolyte interfaces, were simultaneously identified using in situ spectroscopy and further confirmed with isotope-labeling experiments. With AIMD simulations, we report accurate vibrational frequency assignments of these intermediates based on the calculated vibrational density of states and reveal the corresponding species in the electrochemical CO redox landscape on Cu surfaces. Our findings provide direct insights into key intermediates during the CO(2)RR and offer a full-spectroscopic tool (40-4,000 cm-1) for future mechanistic studies.

Escherichia coli BarA-UvrY regulates the pks island and kills Staphylococci via the genotoxin colibactin during interspecies competition.

Wound infections are often polymicrobial in nature, biofilm associated and therefore tolerant to antibiotic therapy, and associated with delayed healing. Escherichia coli and Staphylococcus aureus are among the most frequently cultured pathogens from wound infections. However, little is known about the frequency or consequence of E. coli and S. aureus polymicrobial interactions during wound infections. Here we show that E. coli kills Staphylococci, including S. aureus, both in vitro and in a mouse excisional wound model via the genotoxin, colibactin. Colibactin biosynthesis is encoded by the pks locus, which we identified in nearly 30% of human E. coli wound infection isolates. While it is not clear how colibactin is released from E. coli or how it penetrates target cells, we found that the colibactin intermediate N-myristoyl-D-Asn (NMDA) disrupts the S. aureus membrane. We also show that the BarA-UvrY two component system (TCS) senses the environment created during E. coli and S. aureus mixed species interaction, leading to upregulation of pks island genes. Further, we show that BarA-UvrY acts via the carbon storage global regulatory (Csr) system to control pks expression. Together, our data demonstrate the role of colibactin in interspecies competition and show that it is regulated by BarA-UvrY TCS during interspecies competition.

Innovative wood use can enable carbon-beneficial forest management in California.

Responsible stewardship of temperate forests can address key challenges posed by climate change through sequestering carbon, producing low-carbon products, and mitigating climate risks. Forest thinning and fuel reduction can mitigate climate-related risks like catastrophic wildfire. These treatments are often cost prohibitive, though, in part because of low demand for low-value wood "residues." Where treatment occurs, this low-value wood is often burned or left to decay, releasing carbon. In this study, we demonstrate that innovative use of low-value wood, with improved potential revenues and carbon benefits, can support economical, carbon-beneficial forest management outcomes in California. With increased demand for wood residues, forest health-oriented thinning could produce up to 7.3 million (M) oven-dry tonnes of forest residues per year, an eightfold increase over current levels. Increased management and wood use could yield net climate benefits between 6.4 and 16.9 million tonnes of carbon dioxide equivalent (M tCO2e) per year when considering impacts from management, wildfire, carbon storage in products, and displacement of fossil carbon-intensive alternatives over a 40-y period. We find that products with durable carbon storage confer the greatest benefits, as well as products that reduce emissions in hard-to-decarbonize sectors like industrial heat. Concurrently, treatment could reduce wildfire hazard on 4.9 M ha (12.1 M ac), a quarter of which could experience stand-replacing effects without treatment. Our results suggest that innovative wood use can support widespread fire hazard mitigation and reduce net CO2 emissions in California.

Comparing the effectiveness of two diagnostic approaches for the interpretation of oral radiographic lesions by dental students.

Interpreting radiographic lesions on dental radiographs is a challenging process especially for novice learners, and there is a lack of tools available to support this diagnostic process. This study introduced dental students to two diagnostic aids with contrasting reasoning approaches-ORAD DDx, which uses an analytic, forward reasoning approach, and a Radiographic Atlas, which emphasizes a non-analytic, backward reasoning approach. We compared the effectiveness of ORAD DDx and the Atlas in improving students' diagnostic accuracy and their ability to recall features of radiographic lesions. Participants (99 third-year dental students) were assigned to ORAD DDx, Atlas and Control groups. In the pre-test and post-test, participants provided their diagnosis for eight types of radiographic lesions. All groups also completed a Cued Recall Test. Feedback about ORAD DDx and the Atlas was collected. Results indicated that the Atlas was more effective than ORAD DDx in improving diagnostic accuracy (Estimated marginal mean difference = 1.88 (95% CI 0.30-3.46), p = 0.014, Cohen's d = 0.714). Participants in the Atlas group also outperformed the Control group in the recall of the lesions' radiographic features (Estimated marginal mean difference = 3.42 (95% CI 0.85-5.99), p = 0.005, Cohen's d = 0.793). Students reported that both ORAD DDx and Atlas increased their confidence and decreased the mental effort required to develop differential diagnosis (p ≤ 0.001). This study demonstrates the effectiveness of a non-analytic approach in interpreting dental radiographs among novice learners through the novel use of diagnostic aids.

Ultrarare heterozygous pathogenic variants of genes causing dominant forms of early-onset deafness underlie severe presbycusis.

Presbycusis, or age-related hearing loss (ARHL), is a major public health issue. About half the phenotypic variance has been attributed to genetic factors. Here, we assessed the contribution to presbycusis of ultrarare pathogenic variants, considered indicative of Mendelian forms. We focused on severe presbycusis without environmental or comorbidity risk factors and studied multiplex family age-related hearing loss (mARHL) and simplex/sporadic age-related hearing loss (sARHL) cases and controls with normal hearing by whole-exome sequencing. Ultrarare variants (allele frequency [AF] < 0.0001) of 35 genes responsible for autosomal dominant early-onset forms of deafness, predicted to be pathogenic, were detected in 25.7% of mARHL and 22.7% of sARHL cases vs. 7.5% of controls (P = 0.001); half were previously unknown (AF < 0.000002). MYO6, MYO7A, PTPRQ, and TECTA variants were present in 8.9% of ARHL cases but less than 1% of controls. Evidence for a causal role of variants in presbycusis was provided by pathogenicity prediction programs, documented haploinsufficiency, three-dimensional structure/function analyses, cell biology experiments, and reported early effects. We also established Tmc1N321I/+ mice, carrying the TMC1:p.(Asn327Ile) variant detected in an mARHL case, as a mouse model for a monogenic form of presbycusis. Deafness gene variants can thus result in a continuum of auditory phenotypes. Our findings demonstrate that the genetics of presbycusis is shaped by not only well-studied polygenic risk factors of small effect size revealed by common variants but also, ultrarare variants likely resulting in monogenic forms, thereby paving the way for treatment with emerging inner ear gene therapy.

Surface Water as an Initial Proton Source for the Electrochemical CO Reduction Reaction on Copper Surfaces.

We have employed in situ electrochemical shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) and density functional theory (DFT) calculations to study the CO reduction reaction (CORR) on Cu single-crystal surfaces under various conditions. Coadsorbed and structure-/potential-dependent surface species, including *CO, Cu-Oad , and Cu-OHad , were identified using electrochemical spectroscopy and isotope labeling. The relative abundance of *OH follows a "volcano" trend with applied potentials in aqueous solutions, which is yet absent in absolute alcoholic solutions. Combined with DFT calculations, we propose that the surface H2 O can serve as a strong proton donor for the first protonation step in both the C1 and C2 pathways of CORR at various applied potentials in alkaline electrolytes, leaving adsorbed *OH on the surface. This work provides fresh insights into the initial protonation steps and identity of key interfacial intermediates formed during CORR on Cu surfaces.

Market Potential for CO2 Removal and Sequestration from Renewable Natural Gas Production in California.

Bioenergy with carbon capture and sequestration (BECCS) is critical for stringent climate change mitigation but is commercially and technologically immature and resource intensive. State and federal fuel and climate policies can drive first markets for BECCS in California. We develop a spatially explicit optimization model to assess niche markets for renewable natural gas (RNG) production with carbon capture and sequestration (CCS) from waste biomass in California. Existing biomass residues produce biogas and RNG and enable low-cost CCS through the upgrading process and CO2 truck transport. Under current state and federal policy incentives, RNG-CCS can avoid 12.4 mmtCO2e/year (3% of California's 2018 CO2 emissions), of which 2.9 mmtCO2/year are captured and sequestered. It simultaneously produces 93 PJ RNG/year (4% of California's 2018 natural gas demand) with a profit maximizing objective, resulting in profits of $11/GJ. Distributed RNG production with CCS can potentially catalyze markets and technologies for CO2 capture, transport, and storage in California.

Overcoming the impact of physiologic tremors in ophthalmology.

PURPOSE: Ophthalmic surgery involves the manipulation of micron-level sized structures such as the internal limiting membrane where tactile sensation is practically absent. All humans have physiologic tremors that are of low amplitude and not discernible to the naked eye; they do not adversely affect the majority of the population's daily functioning. However, during microsurgery, such tremors can be problematic. In this review, we focus on the impact of physiological tremors on ophthalmic microsurgery and offer a comparative discussion on the impact of such tremors on other surgical specialties. METHODS: A single investigator used the MEDLINE database (via PubMed) to search for and identify articles for inclusion in this systematic review. Ten key factors were identified as potentially having an impact on tremor amplitude: beta-blockers, muscle fatigue, robotic systems, handheld tools/micromanipulators, armrests/wrist supports, caffeine, diet, sleep deprivation, consuming alcohol, and workouts (exercise). These key terms were then searched using the advanced Boolean search tool and operators (i.e., AND, OR) available on PubMed: (*keyword*) AND (surgeon tremor OR microsurgery tremor OR hand steadiness OR simulator score). RESULTS: Ten studies attempted to quantify the baseline severity of operator physiologic tremor. Approximately 89% of studies accessing the impact of tremors on performance in regards to surgical metrics reported an improvement in performance compared to 57% of studies concluding that tremor elimination was of benefit when considering procedural outcomes. CONCLUSIONS: Robotic technology, new instruments, exoskeletons, technique modifications, and lifestyle factors have all demonstrated the potential to assist in overcoming tremors in ophthalmology.

Social prevalence of knowledge about ectopic pregnancy - tip of the 'health inequalities' iceberg?

We aimed to assess the social and demographic factors determining the level of awareness of the signs and symptoms of ectopic pregnancy (EP) in an East London female population and determine if awareness was related to adverse outcomes. This was a prospective, observational study using a structured questionnaire to assess awareness of EP. A retrospective analysis of a database of EP patients was used to assess the association between adverse clinical outcomes and knowledge about EP. A younger age (<20 years) (p = .024), higher education (p = .008), higher income (p = .002), professional (p = .008), white ethnicity (p= <.00001), single (p = .037) and an awareness of the media (p = .030) were statistically significantly related to a higher knowledge. A significant difference was seen between the white and all other ethnicities in the amount of blood loss (p = .033). The relative risks (RRs 1.169) of having >500 ml of blood loss were higher in the ethnic minorities. RR of >500 ml of blood loss if Asian compared to white is 1.1034 and if black compared to white is 1.1201. Blacks are more likely than whites and Asians to have blood loss >1000 ml (p = .019). An ethnic minority, a lower education level, the older age groups, those with a lower income and with non-professional careers are linked to a lower level of knowledge about EP. Ethnic minority communities have a higher risk of adverse clinical outcomes.Impact StatementWhat is already known on this subject? Research has identified demographic and social factors which prove that victims of health inequalities are usually the poor and the marginalised.What the results of this study add? To-date, our study is the only one to establish that the level of knowledge about ectopic pregnancy (EP) is influenced by demographic and socioeconomic factors and that lower levels of knowledge are significantly associated with adverse clinical outcomes. Our findings show that ethnic minority women are more likely to suffer morbidity from EP than their Caucasian counterparts. We have also established that women of poorer backgrounds, women with lesser levels of education and in non-professional jobs are least likely to be aware of signs and symptoms and consequences of EP.What the implications are of these findings for clinical practice and/or further research? The health service has a responsibility to identify these populations and target them for interventions to correct these health inequalities. We propose a multifaceted plan to increase the level of knowledge of these identified sections of the local community.

Enterococcus faecalis Manganese Exporter MntE Alleviates Manganese Toxicity and Is Required for Mouse Gastrointestinal Colonization.

Bacterial pathogens encounter a variety of nutritional environments in the human host, including nutrient metal restriction and overload. Uptake of manganese (Mn) is essential for Enterococcus faecalis growth and virulence; however, it is not known how this organism prevents Mn toxicity. In this study, we examine the role of the highly conserved MntE transporter in E. faecalis Mn homeostasis and virulence. We show that inactivation of mntE results in growth restriction in the presence of excess Mn, but not other metals, demonstrating its specific role in Mn detoxification. Upon growth in the presence of excess Mn, an mntE mutant accumulates intracellular Mn, iron (Fe), and magnesium (Mg), supporting a role for MntE in Mn and Fe export and a role for Mg in offsetting Mn toxicity. Growth of the mntE mutant in excess Fe also results in increased levels of intracellular Fe, but not Mn or Mg, providing further support for MntE in Fe efflux. Inactivation of mntE in the presence of excess iron also results in the upregulation of glycerol catabolic genes and enhanced biofilm growth, and addition of glycerol is sufficient to augment biofilm growth for both the mntE mutant and its wild-type parental strain, demonstrating that glycerol availability significantly enhances biofilm formation. Finally, we show that mntE contributes to colonization of the antibiotic-treated mouse gastrointestinal (GI) tract, suggesting that E. faecalis encounters excess Mn in this niche. Collectively, these findings demonstrate that the manganese exporter MntE plays a crucial role in E. faecalis metal homeostasis and virulence.

DNABarcodeCompatibility: an R-package for optimizing DNA-barcode combinations in multiplex sequencing experiments.

SUMMARY: Using adequate DNA barcodes is essential to unambiguously identify each DNA library within a multiplexed set of libraries sequenced using next-generation sequencers. We introduce DNABarcodeCompatibility, an R-package that allows one to design single or dual-barcoding multiplex experiments by imposing desired constraints on the barcodes (including sequencer chemistry, barcode pairwise minimal distance and nucleotide content), while optimizing barcode frequency usage, thereby allowing one to both facilitate the demultiplexing step and spare expensive library-preparation kits. The package comes with a user-friendly interface and a web app developed in Java and Shiny (https://dnabarcodecompatibility.pasteur.fr), respectively, with the aim to help bridge the expertise of core facilities with the experimental needs of non-experienced users. AVAILABILITY AND IMPLEMENTATION: DNABarcodeCompatibility can be easily extended to fulfil specific project needs. The source codes of the R-package and its user interfaces are publicly available along with documentation at [https://github.com/comoto-pasteur-fr] under the GPL-2 licence. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Killing with proficiency: Integrated post-translational regulation of an offensive Type VI secretion system.

The Type VI secretion system (T6SS) is widely used by bacterial pathogens as an effective weapon against bacterial competitors and is also deployed against host eukaryotic cells in some cases. It is a contractile nanomachine which delivers toxic effector proteins directly into target cells by dynamic cycles of assembly and firing. Bacterial cells adopt distinct post-translational regulatory strategies for deployment of the T6SS. 'Defensive' T6SSs assemble and fire in response to incoming attacks from aggressive neighbouring cells, and can utilise the Threonine Protein Phosphorylation (TPP) regulatory pathway to achieve this control. However, many T6SSs are 'offensive', firing at all-comers without the need for incoming attack or other cell contact-dependent signal. Post-translational control of the offensive mode has been less well defined but can utilise components of the same TPP pathway. Here, we used the anti-bacterial T6SS of Serratia marcescens to elucidate post-translational regulation of offensive T6SS deployment, using single-cell microscopy and genetic analyses. We show that the integration of the TPP pathway with the negative regulator TagF to control core T6SS machine assembly is conserved between offensive and defensive T6SSs. Signal-dependent PpkA-mediated phosphorylation of Fha is required to overcome inhibition of membrane complex assembly by TagF, whilst PppA-mediated dephosphorylation promotes spatial reorientation and efficient killing. In contrast, the upstream input of the TPP pathway defines regulatory strategy, with a new periplasmic regulator, RtkS, shown to interact with the PpkA kinase in S. marcescens. We propose a model whereby the opposing actions of the TPP pathway and TagF impose a delay on T6SS re-assembly after firing, providing an opportunity for spatial re-orientation of the T6SS in order to maximise the efficiency of competitor cell targeting. Our findings provide a better understanding of how bacterial cells deploy competitive weapons effectively, with implications for the structure and dynamics of varied polymicrobial communities.

Milligram scale production of potent recombinant small interfering RNAs in Escherichia coli.

Small interfering RNAs (siRNAs) are invaluable research tools for studying gene functions in mammalian cells. siRNAs are mainly produced by chemical synthesis or by enzymatic digestion of double-stranded RNA (dsRNA) produced in vitro. Recently, bacterial cells, engineered with ectopic plant viral siRNA binding protein p19, have enabled the production of "recombinant" siRNAs (pro-siRNAs). Here, we describe an optimized methodology for the production of milligram amount of highly potent recombinant pro-siRNAs from Escherichia coli cells. We first optimized bacterial culture medium and tested new designs of pro-siRNA production plasmid. Through the exploration of multiple pro-siRNA related factors, including the expression of p19 protein, (dsRNA) generation method, and the level of RNase III, we developed an optimal pro-siRNA production plasmid. Together with a high-cell density fed-batch fermentation method in a bioreactor, we have achieved a yield of ~10 mg purified pro-siRNA per liter of bacterial culture. The pro-siRNAs produced by the optimized method can achieve high efficiency of gene silencing when used at low nanomolar concentrations. This new method enables fast, economical, and renewable production of pure and highly potent bioengineered pro-siRNAs at the milligram level. Our study also provides important insights into the strategies for optimizing the production of RNA products in bacteria, which is an under-explored field.

The Glycerol-3-Phosphate Acyltransferase GPAT6 from Tomato Plays a Central Role in Fruit Cutin Biosynthesis.

The thick cuticle covering and embedding the epidermal cells of tomato (Solanum lycopersicum) fruit acts not only as a protective barrier against pathogens and water loss but also influences quality traits such as brightness and postharvest shelf-life. In a recent study, we screened a mutant collection of the miniature tomato cultivar Micro-Tom and isolated several glossy fruit mutants in which the abundance of cutin, the polyester component of the cuticle, was strongly reduced. We employed a newly developed mapping-by-sequencing strategy to identify the causal mutation underlying the cutin deficiency in a mutant thereafter named gpat6-a (for glycerol-3-phosphate acyltransferase6). To this end, a backcross population (BC1F2) segregating for the glossy trait was phenotyped. Individuals displaying either a wild-type or a glossy fruit trait were then pooled into bulked populations and submitted to whole-genome sequencing prior to mutation frequency analysis. This revealed that the causal point mutation in the gpat6-a mutant introduces a charged amino acid adjacent to the active site of a GPAT6 enzyme. We further showed that this mutation completely abolished the GPAT activity of the recombinant protein. The gpat6-a mutant showed perturbed pollen formation but, unlike a gpat6 mutant of Arabidopsis (Arabidopsis thaliana), was not male sterile. The most striking phenotype was observed in the mutant fruit, where cuticle thickness, composition, and properties were altered. RNA sequencing analysis highlighted the main processes and pathways that were affected by the mutation at the transcriptional level, which included those associated with lipid, secondary metabolite, and cell wall biosynthesis.

Genome-wide association links candidate genes to resistance to Plum Pox Virus in apricot (Prunus armeniaca).

In fruit tree species, many important traits have been characterized genetically by using single-family descent mapping in progenies segregating for the traits. However, most mapped loci have not been sufficiently resolved to the individual genes due to insufficient progeny sizes for high resolution mapping and the previous lack of whole-genome sequence resources of the study species. To address this problem for Plum Pox Virus (PPV) candidate resistance gene identification in Prunus species, we implemented a genome-wide association (GWA) approach in apricot. This study exploited the broad genetic diversity of the apricot (Prunus armeniaca) germplasm containing resistance to PPV, next-generation sequence-based genotyping, and the high-quality peach (Prunus persica) genome reference sequence for single nucleotide polymorphism (SNP) identification. The results of this GWA study validated previously reported PPV resistance quantitative trait loci (QTL) intervals, highlighted other potential resistance loci, and resolved each to a limited set of candidate genes for further study. This work substantiates the association genetics approach for resolution of QTL to candidate genes in apricot and suggests that this approach could simplify identification of other candidate genes for other marked trait intervals in this germplasm.

Antibacterial effect of ethanolic Gnetum gnemon L. leaf extract on food-borne pathogens and its application as a natural preservative on raw quail eggs.

Gnetum gnemon L. is an evergreen tree that belongs to the Gnetaceae family and is commonly used as a vegetable and medicinal plant among indigenous people. The key goal of this study was to assess the antibacterial efficacy of ethanolic G. gnemon leaf extract (EGLE) against six food-borne pathogens. The antimicrobial activity of EGLE was evaluated using multiple methods, including the well diffusion assay (WDA), minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-kill assay. Gas Chromatography-Mass Spectrometry (GC-MS) analysis was used to identify active volatile compounds responsible for EGLE's antibacterial activities. Total plate count (TPC) was conducted to measure microbial populations and evaluate the efficacy of EGLE as a natural preservative in raw quail eggs. 100 g of dried and powdered sample yielded an average of 11.58 ± 0.38 % post-extraction. The inhibition zone in WDA ranged from 11.00 ± 0.57-13.50 ± 0.58 mm, MIC ranged from 6.25 to 50.00 mg/mL, and MBC values were between 12.5 and >50 mg/mL. Results from the time-kill study showed that at 4 × MIC Bacillus pumilus and B. megaterium were completely killed in 1 h incubation time and other bacteria were killed within 2-4 h. Findings from TPC demonstrated that at the highest tested concentration of EGLE, there was no significant bacterial growth for a 30-day observation period. Thereby, suggesting that it had the potential to function as a natural preservative for raw quail eggs. EGLE may be a viable alternative to synthetic preservatives in combating food-borne pathogens.

Extraction and characterization of cellulose nanoparticles from palm kernel meal for potential application in active food packaging.

The research aimed to explore the potential of palm kernel meal (PKM) as a sustainable source of cellulose nanoparticles (CNPs) for active food packaging. The CNPs were isolated using a combination of chemical techniques, such as alkaline treatment, bleaching, and acid hydrolysis. The characterization of the CNPs was analysed using various techniques, including scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and UV-visible spectroscopy. The findings revealed that chemical processing effectively removed lignin and hemicellulose from PKM. The SEM morphology confirmed the separation of the CNPs, resulting in the production of 40-100 nm spherical cellulose nanoparticles, while XRD and FTIR analyses confirmed their purity and composition. Moreover, the UV-visible spectroscopy exhibited high transmittance rates, indicating the potential of CNPs as reinforcing agents for polymer matrices. The significance of utilising PKM as a valuable fibre source for extracting CNPs can be recommended for developing active food packaging.

The role of intravitreal anti-vascular endothelial growth factor injection in peripheral exudative hemorrhagic chorioretinopathy: A systematic review.

Anti-vascular endothelial growth factor (anti-VEGF) injections have revolutionized the field of ophthalmology, and their use in a variety of retinal diseases is growing. One target disease is peripheral exudative hemorrhagic chorioretinopathy, a disease that is uncommon and poorly understood. Despite this, there are numerous studies and case reports outlining the potential role of intravitreal injection of anti-VEGF medicines to treat it. As such, an evidence-based understanding of its risk-benefit profile is vital. We performed a comprehensive search in the PubMed, Google Scholar, and Cochrane databases for published studies and case reports relating to the use of anti-VEGF injections in peripheral exudative hemorrhagic chorioretinopathy. Anti-VEGF was first used in 2010 to aid in the management of peripheral exudative hemorrhagic chorioretinopathy. Since then, it has been increasingly used to manage this disease. Other potential management strategies, including laser photocoagulation, cryotherapy, photodynamic therapy, and vitrectomy are explored and compared with anti-VEGF where possible. Anti-VEGF appears to be an effective therapy in managing peripheral exudative hemorrhagic chorioretinopathy, especially when there is an exudative threat to the macula.

Mitoxantrone targets both host and bacteria to overcome vancomycin resistance in Enterococcus faecalis.

Antibiotic resistance critically limits treatment options for infection caused by opportunistic pathogens such as enterococci. Here, we investigate the antibiotic and immunological activity of the anticancer agent mitoxantrone (MTX) in vitro and in vivo against vancomycin-resistant Enterococcus faecalis (VRE). We show that, in vitro, MTX is a potent antibiotic against Gram-positive bacteria through induction of reactive oxygen species and DNA damage. MTX also synergizes with vancomycin against VRE, rendering the resistant strains more permeable to MTX. In a murine wound infection model, single-dose MTX treatment effectively reduces VRE numbers, with further reduction when combined with vancomycin. Multiple MTX treatments accelerate wound closure. MTX also promotes macrophage recruitment and proinflammatory cytokine induction at the wound site and augments intracellular bacterial killing in macrophages by up-regulating the expression of lysosomal enzymes. These results show that MTX represents a promising bacterium- and host-targeted therapeutic for overcoming vancomycin resistance.