Transcriptomic responses of 'Huping jujube' (Zizyphus jujuba mill. cv. Huping) fruit to combined treatment of acidic electrolyzed water and high-voltage electrostatic field.

The molecular mechanism underlying the preserving superior quality attributes of postharvest Huping jujube fruit by combining acidic electrolyzed water and high-voltage electrostatic field (AH) treatment remained unclear. The high-throughput sequencing analysis revealed a total of 3590 common differentially expressed genes (DEGs) in the T-W-CK0 vs T-W-CK75 and T-W-CK75 vs T-W-AH75 groups. AH treatment down-regulated most genes associated with respiratory metabolism, as well as lignin and anthocyanin biosynthesis, thereby maintaining lower physiological activities, improving taste and color quality of mature-white jujube. Additionally, AH treatment downregulated the genes involved in reactive oxygen species (ROS) generation and disease resistance, while simultaneously upregulating the genes associated with ROS elimination. This suggested that AH treatment could inhibit pathogen infection to prevent the activation of plants' active defense and reduce the ROS-induced damage. In sum, the present study provided a comprehension explanation that AH treatment improved the storage quality attributes of jujube fruit at the genetic level.

Colourful staples on your table: Unus ex genere suo.

The positive health benefits of colored staples have led to a significant increase in interest in them as healthy food ingredients. Numerous in vitro and in vivo studies have demonstrated that colored cereals are rich in antioxidants, carotenoids, and xanthophylls, which are widely used as natural additives in the food industry. Additionally, shifts in consumer preferences have led to a preference for nutritionally balanced diets over traditional high-energy ones. Thus, colored cereals offer additional nutritional value that has been previously untapped. Besides providing essential nutrients, these natural pigments also have the potential to replace synthetic colors and food additives. This review aims to provide insights into the nutritional value of various colored staples compared to conventional starchy staples and their associated health benefits. Colored staples can be incorporated into daily diets, offering a nutritious and healthful addition to the table.

Unearthing the power of microbes as plant microbiome for sustainable agriculture.

In recent years, research into the complex interactions and crosstalk between plants and their associated microbiota, collectively known as the plant microbiome has revealed the pivotal role of microbial communities for promoting plant growth and health. Plants have evolved intricate relationships with a diverse array of microorganisms inhabiting their roots, leaves, and other plant tissues. This microbiota mainly includes bacteria, archaea, fungi, protozoans, and viruses, forming a dynamic and interconnected network within and around the plant. Through mutualistic or cooperative interactions, these microbes contribute to various aspects of plant health and development. The direct mechanisms of the plant microbiome include the enhancement of plant growth and development through nutrient acquisition. Microbes have the ability to solubilize essential minerals, fix atmospheric nitrogen, and convert organic matter into accessible forms, thereby augmenting the nutrient pool available to the plant. Additionally, the microbiome helps plants to withstand biotic and abiotic stresses, such as pathogen attacks and adverse environmental conditions, by priming the plant's immune responses, antagonizing phytopathogens, and improving stress tolerance. Furthermore, the plant microbiome plays a vital role in phytohormone regulation, facilitating hormonal balance within the plant. This regulation influences various growth processes, including root development, flowering, and fruiting. Microbial communities can also produce secondary metabolites, which directly or indirectly promote plant growth, development, and health. Understanding the functional potential of the plant microbiome has led to innovative agricultural practices, such as microbiome-based biofertilizers and biopesticides, which harness the power of beneficial microorganisms to enhance crop yields while reducing the dependency on chemical inputs. In the present review, we discuss and highlight research gaps regarding the plant microbiome and how the plant microbiome can be used as a source of single and synthetic bioinoculants for plant growth and health.

An integrated perspective on measuring cytokines to inform CAR-T bioprocessing.

Chimeric antigen receptor (CAR)-T cells are emerging as a generation-defining therapeutic however their manufacture remains a major barrier to meeting increased market demand. Monitoring critical quality attributes (CQAs) and critical process parameters (CPPs) during manufacture would vastly enrich acquired information related to the process and product, providing feedback to enable real-time decision making. Here we identify specific CAR-T cytokines as value-adding analytes and discuss their roles as plausible CPPs and CQAs. High sensitivity sensing technologies which can be easily integrated into manufacture workflows are essential to implement real-time monitoring of these cytokines. We therefore present biosensors as enabling technologies and evaluate recent advancements in cytokine detection in cell cultures, offering promising translatability to CAR-T biomanufacture. Finally, we outline emerging sensing technologies with future promise, and provide an overall outlook on existing gaps to implementation and the optimal sensing platform to enable cytokine monitoring in CAR-T biomanufacture.

Effect of spatial relationship between curves on crash severity at horizontal curves in a mountainous terrain.

The study aimed to model the effect of spatial relationship between adjacent curves on the severity of curve-based crashes along with driver and crash causal characteristics, reflecting driver's short-term expectancy. The crash and other associated data was retrieved from the web-based Road Accident Data Management System available in Himachal Pradesh, India, and curvature attributes were extracted using GIS. Overall, the study included 1113 curve based crashes. The driver's perception of the sharpness of a curve was quantified as a single representative categorical factor based simultaneously on its length and radius using K-Medoid Clustering. Separate crash severity models catering to the two possible approach directions of the subject curve were developed reflecting its independent interaction with its corresponding adjacent curve in each direction. Partial Proportional Odds models were developed to overcome the predictive limitations of Ordinal and Multinomial logit models. Indicators of spatial relationship and the intensity of sharpness of the subject curve were found to be statistically significant. A sharp approach curve (radius:40-60 m) increased the risk of fatality by 2.16 times with a similar increase (2.5 times) observed for a short (length:30-60 m) adjacent curve. Adjacent curves turning in the same direction were 2.34 times more prone to fatalities. A very sharp subject curve with radius ≤ 40 m increased the risk of fatal crashes by 2.5 times, as did the short subject curves (30-60 m) (at least 3 times). Subject curves characterized by a short length and a very sharp curvature contributed relatively 3-4 times more to fatal crashes. The identified risk factors and their impact can help the relevant stakeholders to take appropriate actions and can further assist them in identifying high risk scenarios.

Candida spp. isolated from recreational coastal waters of Rio de Janeiro - Brazil: Focus on antifungal resistance and virulence attributes.

The use of recreational waters is a widespread activity worldwide, and one of the risks associated with this practice is the exposure of bathers to microorganisms that may arise due to pollution caused by inadequate infrastructure and sanitation. In the present work, we isolated Candida spp. (n = 24) from five recreational beaches in Rio de Janeiro, Brazil, in order to evaluate their susceptibility to antifungals, the production of virulence attributes and the in vivo virulence using Tenebrio molitor larvae as a model. The ITS1-5.8S-ITS2 gene sequencing identified thirteen isolates (54.1 %) as C. tropicalis, seven (29.1 %) as C. krusei (Pichia kudriavzevii), one (4.2 %) as C. rugosa (Diutina rugosa), one (4.2 %) as C. mesorugosa (Diutina mesorugosa), one (4.2 %) as C. utilis (Cyberlindnera jadinii) and one (4.2 %) as C. parapsilosis. C. tropicalis isolates showed resistance to azoles and susceptibility to amphotericin B, flucytosine and caspofungin. C. krusei isolates were resistant to fluconazole, caspofungin and itraconazole, with 42.8 % resistance to flucytosine, besides susceptibility to voriconazole and amphotericin B. The remaining species were susceptible to all tested antifungals. All Candida isolates adhered to abiotic surfaces and formed biofilm on polystyrene, albeit to varying degrees, and produced aspartic protease and hemolytic activity, which are considered fungal virulence attributes. C. tropicalis, C. krusei and C. utilis isolates produced phytase, while the only esterase producer was C. tropicalis. Regarding resistance to osmotic stress, all isolates of C. tropicalis, C. parapsilosis and C. mesorugosa grew up to 7.5 % NaCl; the remaining isolates grew up to 1.87-3.75 % NaCl. The mortality caused by fungal challenges in T. molitor larvae was variable, with C. tropicalis, C. utilis and C. parapsilosis being more virulent than C. krusei and C. rugosa complex. Collectively, the presence of these yeasts, particularly the virulent and resistant isolates, in recreational waters can pose a significant health risk to bathers.

Multi-scale brain attributes contribute to the distribution of diffuse glioma subtypes.

Gliomas are primary brain tumors and are among the most malignant types. Adult-type diffuse gliomas can be classified based on their histological and molecular signatures as IDH-wildtype glioblastoma, IDH-mutant astrocytoma, and IDH-mutant and 1p/19q-codeleted oligodendroglioma. Recent studies have shown that each subtype of glioma has its own specific distribution pattern. However, the mechanisms underlying the specific distributions of glioma subtypes are not entirely clear despite partial explanations such as cell origin. To investigate the impact of multi-scale brain attributes on glioma distribution, we constructed cumulative frequency maps for diffuse glioma subtypes based on T1w structural images and evaluated the spatial correlation between tumor frequency and diverse brain attributes, including postmortem gene expression, functional connectivity metrics, cerebral perfusion, glucose metabolism, and neurotransmitter signaling. Regression models were constructed to evaluate the contribution of these factors to the anatomic distribution of different glioma subtypes. Our findings revealed that the three different subtypes of gliomas had distinct distribution patterns, showing spatial preferences toward different brain environmental attributes. Glioblastomas were especially likely to occur in regions enriched with synapse-related pathways and diverse neurotransmitter receptors. Astrocytomas and oligodendrogliomas preferentially occurred in areas enriched with genes associated with neutrophil-mediated immune responses. The functional network characteristics and neurotransmitter distribution also contributed to oligodendroglioma distribution. Our results suggest that different brain transcriptomic, neurotransmitter, and connectomic attributes are the factors that determine the specific distributions of glioma subtypes. These findings highlight the importance of bridging diverse scales of biological organization when studying neurological dysfunction.

AC-ModNet: Molecular Reverse Design Network Based on Attribute Classification.

Deep generative models are becoming a tool of choice for exploring the molecular space. One important application area of deep generative models is the reverse design of drug compounds for given attributes (solubility, ease of synthesis, etc.). Although there are many generative models, these models cannot generate specific intervals of attributes. This paper proposes a AC-ModNet model that effectively combines VAE with AC-GAN to generate molecular structures in specific attribute intervals. The AC-ModNet is trained and evaluated using the open 250K ZINC dataset. In comparison with related models, our method performs best in the FCD and Frag model evaluation indicators. Moreover, we prove the AC-ModNet created molecules have potential application value in drug design by comparing and analyzing them with medical records in the PubChem database. The results of this paper will provide a new method for machine learning drug reverse design.

Unveiling the efficacy of Bacillus faecalis and composted biochar in alleviating arsenic toxicity in maize.

Arsenic (As) contamination is a major environmental pollutant that adversely affects plant physiological processes and can hinder nutrients and water availability. Such conditions ultimately resulted in stunted growth, low yield, and poor plant health. Using rhizobacteria and composted biochar (ECB) can effectively overcome this problem. Rhizobacteria have the potential to enhance plant growth by promoting nutrient uptake, producing growth hormones, and suppressing diseases. Composted biochar can enhance plant growth by improving aeration, water retention, and nutrient cycling. Its porous structure supports beneficial microorganisms, increasing nutrient uptake and resilience to stressors, ultimately boosting yields while sequestering carbon. Therefore, the current study was conducted to investigate the combined effect of previously isolated Bacillus faecalis (B. faecalis) and ECB as amendments on maize cultivated under different As levels (0, 300, 600 mg As/kg soil). Four treatments (control, 0.5% composted biochar (0.5ECB), B. faecalis, and 0.5ECB + B. faecalis) were applied in four replications following a completely randomized design. Results showed that the 0.5ECB + B. faecalis treatment led to a significant rise in maize plant height (~ 99%), shoot length (~ 55%), root length (~ 82%), shoot fresh (~ 87%), and shoot dry weight (~ 96%), root fresh (~ 97%), and dry weight (~ 91%) over the control under 600As stress. There was a notable increase in maize chlorophyll a (~ 99%), chlorophyll b (~ 81%), total chlorophyll (~ 94%), and shoot N, P, and K concentration compared to control under As stress, also showing the potential of 0.5ECB + B. faecalis treatment. Consequently, the findings suggest that applying 0.5ECB + B. faecalis is a strategy for alleviating As stress in maize plants.

Foliar-applied melatonin and titanium nanoparticles modulate cadmium (Cd) toxicity through minimizing Cd accumulation and optimizing physiological and biochemical properties in sage (Salvia officinalis L.).

Notwithstanding the fact that melatonin (MT) and titanium nanoparticles (Ti NPs) alone have been widely used recently to modulate cadmium (Cd) stress in plants, there is a gap in the comparative impacts of these materials on lowering Cd toxicity in sage plants. The objective of this study was to determine how foliar application of MT and Ti NPs affected the growth, Cd accumulation, photosynthesis, water content, lipid peroxidation, and essential oil (EO) quality and quantity of sage plants in Cd-contaminated soils. A factorial experiment was conducted using MT at 100 and 200 µM and Ti NPs at 50 and 100 mg L-1 topically, together with Cd toxicity at 10 and 20 mg Cd kg-1 soil. The results showed that Cd toxicity decreased plant growth and enhanced lipid peroxidation. The Cd stress at 20 mg kg-1 soil resulted in increases in Cd root (693%), Cd shoot (429%), electrolyte leakage (EL, 29%), malondialdehyde (MDA, 72%), shoot weight (31%), root weight (27%), chlorophyll (Chl) a + b (26%), relative water content (RWC, 23%), and EO yield (30%). The application of MT and Ti NPs controlled drought stress by reducing MDA and EL, enhancing plant weight, Chl, RWC, and EO production, and minimizing Cd accumulation in plant tissues. The predominant compounds in the EO were α-thujone, 1,8-cineole, ß-thujone, camphor, and α-humulene. MT and Ti NPs caused α-thujone to rise, whereas Cd stress caused it to fall. Based on heat map analysis, MDA was the trait that was most sensitive to treatments. In summary, the research emphasizes the possibility of MT and Ti NPs, particularly MT at 200 µM, to mitigate Cd toxicity in sage plants and enhance their biochemical reactions.

[Extraction process optimization and link evaluation of Reyanning Mixture based on quality by design idea].

Reyanning Mixture is one of the superior Chinese patent medicine varieties of "Qin medicine". Based on the idea of quality by design(QbD), the extraction process of the Reyanning Mixture was optimized. The caffeic acid, polydatin, resveratrol, and emodin were used as critical quality attributes(CQAs). The material-liquid ratio, extraction temperature, and extraction time were taken as critical process parameters(CPPs) by the Plackett-Burman test. The mathematical model was established by the star design-effect surface method, and the design space was constructed and verified. The optimal extraction process of the Reyanning Mixture was obtained as follows: material-liquid ratio of 11.84 g·mL~(-1), extraction temperature at 81 ℃, and two extractions. A partial least-square(PLS) quantitative model for CQAs was established by using near-infrared spectroscopy(NIRS) combined with high-performance liquid chromatography(HPLC) under the optimal extraction process. The results showed that the correlation coefficients of the correction set(R_c) and validation set(R_p) of the quantitative models of four CQAs were more than 0.9. The root mean square error of the correction set(RMSEC) were 0.744, 6.71, 3.95, and 1.53 µg·mL~(-1), respectively, and the root mean square error of the validation set(RMSEP) were 0.709, 5.88, 2.92, and 1.59 µg·mL~(-1), respectively. Therefore, the optimized extraction process of the Reyanning Mixture is reasonable, feasible, stable, and reliable. The NIRS quantitative model has a good prediction, which can be used for the rapid content determination of CQAs during extraction. They can provide an experimental basis for the process research and quality control of Reyanning Mixture.

A Systematic Review of the Effect of Stigmatization on Psychiatric Illness Outcomes.

A significant proportion of individuals with psychiatric disorders face dual challenges such as managing the symptoms and disabilities of their conditions and enduring stigma arising from misconceptions about mental illness. This stigma denies them quality-of-life opportunities, such as access to satisfactory healthcare services, better employment, safer housing, and social affiliations. This systematic review aims to evaluate the effect of stigmatization on psychiatric illness outcomes, particularly its influence on treatment adherence, treatment-seeking behavior, and care outcomes. We conducted a systematic review of 39 studies published between 2010 and 2024, focusing on the effects of stigmatization on psychiatric illness outcomes. The review utilized robust methodology following Cochrane guidance and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, including studies from 2010 to 2024 obtained from databases such as PubMed, Embase, Google Scholar, Web of Science, and SCOPUS. The quality of the included studies was assessed using the Appraisal Tool for Cross-Sectional Studies, with most studies rated as moderate to high quality. The findings indicate that stigma in psychiatric illness is closely associated with several factors, including illness duration (mean effect size = 0.42, p < 0.05), frequency of clinic visits (mean reduction = 2.3 visits/year), and diagnosis of psychotic disorders (OR = 1.78, 95% CI: 1.20-2.65). Stigma manifests through misinformation, prejudice, and discrimination, leading to significant barriers to accessing and adhering to psychiatric treatment, thereby worsening health outcomes. It leads to delays in accessing healthcare, poor adherence to medication and follow-up, and negative psychiatric health outcomes, including disempowerment, reduced self-efficacy, increased psychiatric symptoms, and decreased quality of life. Also, stigma extends to caregivers and healthcare professionals, complicating care delivery. This review highlights the need for effective interventions and strategies to address stigma, emphasizing the importance of educational interventions to mitigate the adverse effects of public stigma. Understanding the multifaceted nature of stigma is crucial for developing targeted approaches to improve psychiatric care outcomes and ensure better mental health services for individuals with mental illnesses.

Ensuring People Living with HIV Inform the Future of HIV Treatment in Low- and Middle-Income Countries: A Scoping Review and Recommendations for a Community-Led Research Agenda.

The HIV treatment landscape in low- and middle-income countries (LMICs) is rapidly evolving, exemplified by the expansion of differentiated service delivery (DSD) during the coronavirus disease (COVID-19) pandemic. Long-acting products represent a new frontier that will require a significant redesign of health systems. It is critical to understand service delivery and product preferences of people living with HIV (PLHIV) and ensure evidence generation is guided by community priorities. We conducted a scoping review to identify gaps among preference studies and inform future research. Peer-reviewed articles published from January 2014-May 2022 reporting acceptability or preference data from PLHIV or caregivers for one or more service delivery or product attribute were eligible. Service delivery studies were restricted to LMIC populations while product studies had no geographical restrictions. Based on gaps identified, we consulted advocates to develop community-led research agenda recommendations. Of 6,493 studies identified, 225 studies on service delivery attributes and 47 studies on product preferences were eligible. The most frequently studied delivery models were integration (n = 59) and technology-based interventions (n = 55). Among product literature, only 15 studies included LMIC populations. Consultation with advocates highlighted the need for research on long-acting products, including among pediatric, pregnant, and breastfeeding PLHIV, PLHIV on second-line regimens, and key populations. Consultation also emphasized the need to understand preferences on clinic visit frequency, side effects, and choice. While the preference literature has expanded, gaps remain around long-acting regimens and their delivery. To fill these gaps, the research agenda must be guided by the priorities of communities of PLHIV.

Testing the feasibility and preliminary efficacy of Meaningful Activity for Managing Behavioral Symptoms of Distress (MAC-4-BSD) intervention for residents with dementia in assisted living: Protocol description.

The purpose of this manuscript is to describe the protocol for an Alzheimer's Association-funded cluster randomized trial that focuses on engaging assisted living residents with dementia in meaningful activity to help address their behavioral symptoms of distress using a theoretically based approach, Meaningful Activity for Managing Behavioral Symptoms of Distress (MAC-4-BSD). The development of MAC-4-BSD was based on the Social Ecological Model and Social Cognitive Theory. The MAC-4-BSD intervention includes the following four steps: (1) Assessment of the assisted living physical environment and policies to facilitate meaningful activity; (2) Education of staff about implementation of meaningful activity; (3) Assessment of resident preferences and goals for meaningful activity; (4) Mentoring and motivating staff and residents to facilitate engagement in meaningful activity. The overall aim of this study will be to determine the feasibility and preliminary efficacy of implementing the MAC-4-BSD intervention and test whether it will improve residents' engagement in meaningful activity, behavioral symptoms of distress, and quality of life as well as the environment and policies to promote meaningful activity in assisted living.

Design and Development of Ophthalmic Liposomes from the QbD Perspective.

Due to significant lachrymation, drug washing out, and poor adhesion to the lipophilic outer layer of the precorneal and cornea membrane, topical ophthalmic solution drops have poor ocular bioavailability. The rate of transcorneal absorption is impacted in the case of hydrophilic drug molecules as brimonidine tartrate, timolol maleate, cyclosporine, etc. Ophthalmic solution administered in many doses is less patient-compliant. The limitation of multiple-dose and its negative effects can be overcome by the development of delayed- release liposomes. Liposomes are regulatory-approved novel drug delivery systems. Its vesicular form aids in delaying medication release, and its lipidic makeup enables it to stick to the cornea's lipophilic layer. As a result, it will prevent precorneal clearing, extend corneal contact time, and provide sufficient transcorneal absorption. The aim of this review article is to portray the benefits of liposomes for ophthalmic drug delivery and its formulation development in the light of QbD. The review discusses the composition, preparatory methods and quality aspects of ophthalmic liposomes. It then accordingly reasonably proposes the quality target product profile, critical quality attributes, critical material attributes and critical process parameters, involved in liposome development for ophthalmic drug delivery. This review shall help formulation scientists to formulate ophthalmic liposomes of desirable quality.

A preliminary study to identify critical factors for evaluating the effect of car-lock sounds on drivers.

Car-lock sounds are designed to inform the lock status of vehicles. However, drivers often experience a lack of confidence regarding whether the car is locked, and car thefts persistently occur, frequently attributed to unlocked doors. Without identification of critical factors for evaluating effects of car-lock sounds on drivers, a strategy to car-lock sound design with increased locking efficiency remains implicit. This study proposes a method to identify critical factors influencing drivers' perceived certainty of car-lock status and behaviours during car-locking. An experiment was conducted to simulate the locking process and verbal protocol analysis was employed to comprehend participants' cognitive processes and behaviours. The results show that mechanical sound yielded high certainty and few hesitations, while tonal and crisp sound elicited low certainty and frequent hesitations. Seven critical factors on participants' behaviours and cognitive processes were identified, which provides a data-driven approach for future research in car-lock sounds evaluation and design.

The effect of car-lock sounds on drivers is significant to inform the locking status of vehicles. However, the strategy for car-lock sounds evaluation remains implicit. This study proposes a method to identify critical factors on drivers' behaviours and cognitive processes that would inform further car-lock sounds evaluation and design.

The contribution of commonly consumed edible insects to nutrition security in the Eastern D.R. Congo.

Edible insects are perceived as an incredible opportunity to mitigate the major challenge of sustainably producing healthy foods for a growing world population in the face of climate change uncertainties over the coming decade. In this study, we assessed the nutrient composition and sensory properties of Acheta domesticus, Apis mellifera, Gnathocera trivittata, Gryllotalpa africana, Imbrasia epimethea, Imbrasia oyemensis, Locusta migratoria, Macrotermes subhylanus, Nomadacris septemfasciata, Rhyncophorus phoenicis, Ruspolia differens and Rhynchophorus ferrugineus consumed in Eastern D. R. Congo. The investigated edible insects are highly appreciated and nutritious, with proteins (20.67-43.93 g/100 g) and fats (14.53-36.02 g/100 g) being the major macro-nutrients, proving their potential to improve diets through food enrichment. The high potassium (24-386.67 mg/100 g), sodium (152-257.82 mg/100 g), magnesium (32-64 mg/100 g), iron (5.3-16.13 mg/100 g), calcium (25-156.67 mg/100 g) and zinc (11-19.67 mg/100 g) content make the assessed edible insects a useful mineral-containing ingredient for preventing undernutrition in countries which are plagued by micronutrient deficiencies. A scatter plot of matrices and Pearson's correlations between sensory attributes and nutritional composition showed a negative correlation (r = - 0.45) between protein and appearance. While no strong correlation was observed between nutritional attributes and sensory acceptance, a positive correlation was observed between potassium and aroma (r = 0.50), after-taste (r = 0.50) and acceptability (r = 0.52). Principal component analysis results indicated that the two axes accounted for up to 97.4% of the observed variability in the nutrient composition and sensory attributes of commonly consumed edible insects in the Eastern D. R. Congo. Given the significant delicacy and nutritional potential of edible insects highlighted in this paper, households can rely on the latter to meet their nutritional needs rather than conventional livestock, thus contributing to environmental and financial security through local business opportunities.

Fish Waste-A Novel Bio-Fertilizer for Stevia (Stevia rebaudiana Bertoni) under Salinity-Induced Stress.

Currently, different strategies, including the application of bio-fertilizers, are used to ameliorate the adverse effects posed by salinity stress as the major global problem in plants. Fish waste is suggested as a novel bio-fertilizer to mitigate the effects of biotic and abiotic stresses. In this investigation, an experiment was conducted to investigate the effects by applying different concentrations (0, 5, 10, and 15% (v/v)) of fish waste bio-fertilizer on stevia plants grown under salt stress conditions (0, 20, 40, and 60 mM of NaCl). Results showed that salinity negatively affected growth parameters, the photosynthetic pigments, the relative water content, and the chlorophyll fluorescence parameters while increased the activity of antioxidant enzymes, total phenol, hydrogen peroxide (H2O2), malondialdehyde (MDA), proline, and total carbohydrates compared with control samples. On the other hand, the application of fish waste bio-fertilizer mitigated the effects of salinity stress by enhancing growth and mitigating stress-relative markers, especially at the highest salinity level (60 mM). Overall, fish waste bio-fertilizer could be considered a sustainable, innovative approach for the alleviation of salinity stress effects in plants and, in addition, fish waste bio-fertilizer did not cause more salinity issues, at least with the applied doses and experiment time, which is an imperative aspect.

Risk-Based Approach for Defining Retest Dates for Active Pharmaceutical Ingredients and Excipients.

Drug substances and excipients must be stored in recommended storage conditions and should comply with their specifications during the retest period for their use in the manufacture of drug products. The ICH (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use) and WHO (World Health Organization) regulatory guidelines mandate that after the retest period, the drug substances must be retested for compliance with the specification and then used immediately in the manufacture of the finished product. Although these substances can be retested multiple times, an emphasis is placed on immediate use following a retest and compliance with standards. The phrase "used immediately" is ambiguous and is left for interpretation. In this article, we will look at the various processes that must be completed to determine the retest date. In addition, we present a risk-based method for establishing retest dates and the time during which material can be used.

Ratanjot (Alkanna tinctoria L.) Root Extract, Rich in Antioxidants, Exhibits Strong Antimicrobial Activity against Foodborne Pathogens and Is a Potential Food Preservative.

Natural and sustainable plant-based antioxidants and antimicrobials are highly desirable for improving food quality and safety. The present investigation assessed the antimicrobial and antioxidant properties of active components from Alkanna tinctoria L. (herb) roots, also known as Ratanjot root. Two methods were used to extract active components: microwave-assisted hot water (MAHW) and ethanolic extraction. MAHW extract yielded 6.29%, while the ethanol extract yielded 18.27%, suggesting superior Ratanjot root extract powder (RRP) solubility in ethanol over water. The ethanol extract showed significantly higher antioxidant activity than the MAHW extract. Gas Chromatography-Mass Spectrometry analysis revealed three major phenolic compounds: butanoic acid, 3-hydroxy-3-methyl-; arnebin 7, and diisooctyl pthalate. The color attributes (L*, a*, b*, H°ab, C*ab) for the ethanolic and MAHW extracts revealed significant differences (p < 0.05) in all the above parameters for both types of extracts, except for yellowness (b*) and chroma (C*ab) values. The ethanol extract exhibited antimicrobial activity against 14 foodborne bacteria, with a significantly higher inhibitory effect against Gram-positive bacteria (Listeria monocytogenes and Staphylococcus aureus) than the Gram-negative bacteria (Salmonella enterica serovar Typhimurium and Escherichia coli). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were both 25 mg/mL for the Gram-negative bacteria, while the MIC and MBC concentrations varied for Gram-positive bacteria (0.049-0.098 mg/mL and 0.098-0.195 mg/mL) and the antimicrobial effect was bactericidal. The antimicrobial activities of RRP extract remained stable under broad temperature (37-100 °C) and pH (2-6) conditions, as well as during refrigerated storage for 30 days. Application of RRP at 1% (10 mg/g) and 2.5% (25 mg/g) levels in a cooked chicken meatball model system prevented lipid oxidation and improved sensory attributes and retarded microbial growth during refrigerated (4 °C) storage for 20 days. Furthermore, the RRP extract was non-toxic when tested with sheep erythrocytes and did not inhibit the growth of probiotics, Lacticaseibacillus casei, and Lactiplantibacillus plantarum. In conclusion, the study suggests that RRP possesses excellent antimicrobial and antioxidant activities, thus making it suitable for food preservation.