bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing Green Innovations in the Wine Industry: An Applied Analysis
Authors: Sánchez-García Eduardo , Martínez-Falcó Javier , Alcon-Vila Antonio , Marco-Lajara Bartolomé
Published: March 2023

Winemaking is an ancestral activity characterized by its strong roots in the culture, heritage, and people of the producing regions. In addition to providing important health benefits, wine is a product that is widely accepted by society. However, the socioeconomic context is evolving at a rapid pace, and new requirements and needs are forcing companies to innovate in order to remain competitive in the markets, especially in terms of sustainability. The main aim of this paper is to analyze the relationship between green transformational leadership and green innovation, as well as the mediating effect of green motivation and green creativity in this relationship. Data were obtained from a sample of 196 Spanish companies belonging to the wine industry and, as a method of analysis, was used partial least squares structural equation modeling PLS-SEM. The results show a positive and significant relationship between green transformational leadership and green innovation in wine companies. Furthermore, green motivation and green creativity exert a mediating effect in this relationship. It is concluded that the managers of wine companies should encourage employee motivation and creativity, especially in ecological terms, by creating an environment conducive to the development of environmentally friendly innovations.
Application of Fixed Points in Bipolar Controlled Metric Space to Solve Fractional Differential Equation
Authors: Mani Gunaseelan , Ramaswamy Rajagopalan , Gnanaprakasam Arul Joseph , Elsonbaty Amr , Abdelnaby Ola A. Ashour , Radenović Stojan
Published: March 2023

Fixed point results and metric fixed point theory play a vital role to find the unique solution to differential and integral equations. Likewise, fractal calculus has vast physical applications. In this article, we introduce the concept of bipolar-controlled metric space and prove fixed point theorems. The derived results expand and extend certain well-known results from the research literature and are supported with a non-trivial example. We have applied the fixed point result to find the analytical solution to the integral equation and fractional differential equation. The analytical solution has been supplemented with numerical simulation.
Fractional Model of Multiple Trapping with Charge Leakage: Transient Photoconductivity and Transit–Time Dispersion
Authors: Serdouk Fadila , Boumali Abdelmalek , Sibatov Renat T.
Published: March 2023

The model of multiple trapping into energy-distributed states is a successful tool to describe the transport of nonequilibrium charge carriers in amorphous semiconductors. Under certain conditions, the model leads to anomalous diffusion equations that contain time fractional derivatives. From this perspective, the multiple-trapping model can be used to interpret fractional transport equations, formulate initial and boundary conditions for them, and to construct numerical methods for solving fractional kinetic equations. Here, we shortly review the application of fractional multiple-trapping equations to problems of transient photoconductivity relaxation and transit–time dispersion in the time-of-flight experiment and discuss the connection of the multiple-trapping model with generalized fractional kinetic equations. Different types of charge leakage are discussed. The tempered fractional relaxation is obtained for recombination via localized states and distributed order equations arise for the non-exponential density of states presented as a weighted mixture of exponential functions. Analytical solutions for photocurrent decay in transient photoconductivity and time-of-flight experiments are provided for several simplified situations.
Novel Variants in the VCP Gene Causing Multisystem Proteinopathy 1
Authors: Columbres Rod Carlo Agram , Chin Yue , Pratti Sanjana , Quinn Colin , Gonzalez-Cuyar Luis F. , Weiss Michael , Quintero-Rivera Fabiola , Kimonis Virginia
Published: March 2023

Valosin-containing protein (VCP) gene mutations have been associated with a rare autosomal dominant, adult-onset progressive disease known as multisystem proteinopathy 1 (MSP1), or inclusion body myopathy (IBM), Paget’s disease of bone (PDB), frontotemporal dementia (FTD), (IBMPFD), and amyotrophic lateral sclerosis (ALS). We report the clinical and genetic analysis findings in five patients, three from the same family, with novel VCP gene variants: NM_007126.5 c.1106T>C (p.I369T), c.478G>A (p.A160T), and c.760A>T (p.I254F), associated with cardinal MSP1 manifestations including myopathy, PDB, and FTD. Our report adds to the spectrum of heterozygous pathogenic variants found in the VCP gene and the high degree of clinical heterogeneity. This case series prompts increased awareness and early consideration of MSP1 in the differential diagnosis of myopathies and/or PDB, dementia, or ALS to improve the diagnosis and early management of clinical symptoms.
Addressing the Endometriosis Knowledge Gap for Improved Clinical Care—A Cross-Sectional Pre- and Post-Educational-Intervention Study among Pakistani Women
Authors: Saad Muhammad , Rafiq Aiman , Jamil Anam , Sarfraz Zouina , Sarfraz Azza , Robles-Velasco Karla , Cherrez-Ojeda Ivan
Published: March 2023

This study explored the baseline knowledge and symptoms associated with endometriosis, educated women about endometriosis, and documented the improvement in endometriosis knowledge. A brief intervention with an educational brochure on endometriosis was administered among 303 female participants. A paired-sample t-test and one-way ANOVA were run to compute endometriosis knowledge scores. In total, 49.5% of the participants had consistent access to annual healthcare, 25.1% were healthcare workers, and 45.2% had an undergraduate education. The entire sample had a pre-test endometriosis knowledge score of 4.2 (SD = 2.48), and the score was 6.3 (SD = 2.3) on the post-test. One-way ANOVA yielded no significant improvement in knowledge scores across the groups with consistent and inconsistent access to annual healthcare, despite a significant overall increase in scores (t = 16.63, df = 302, p < 0.001). We identified a significant improvement in the knowledge concerning endometriosis. Educational strategies among women who are menstruating are essential for addressing diagnostic delays and bridging the endometriosis knowledge gap.
Changing Insect Catch in Viennese Museums during COVID-19
Authors: Brimblecombe Peter , Querner Pascal
Published: March 2023

The COVID-19 pandemic led to significant changes in societies across the globe. In many countries in Europe, national lockdowns during the spring of 2020 meant that museums were closed, and maintenance and housekeeping were at a minimum. We compared the insect monitoring data of 15 museums in and around Vienna between the years 2018 and 2022 to see potential effects of the two lockdowns (spring 2020 and winter 2020/21) on insect populations. In Vienna, these changes altered the presence of pests, most notably an increase in silverfish by late spring (March–May 2020). We also found increased numbers of other pest species (notably Tineola bisselliella and Attagenus sp.), though these changes were seen later (June–October 2020). Thylodrias contractus, although found only in one museum, appeared to show decreased numbers during 2020. Storage areas in some of the museums revealed no significant increase in insect catch during the COVID-19 related closures. Since there are rarely visitors in such spaces, the situation did not change much during the closures. Silverfish are shy insects, but they were able to range more freely during the closures in the mostly darkened rooms. The increase of Tineola bisselliella and Attagenus sp. could be a result of reduced cleaning in the first lockdown. In the second lockdown, no significant changes were found. Human activity from staff was much higher compared to the first closure; a second reason could be the time of year, as in the winter period, it is mainly larvae that are active. Increased insect populations remind us that even when museums are unoccupied, they still need monitoring for possible risks from pests. No damage to the objects from the pests was observed in the museums investigated.
Insecticide Efficacy against Earias Species Infestation of Okra and Residue Analysis of Chlorantraniliprole under Field Conditions in India
Authors: Sheoran Sindhu , Kalkal Deepika , Chauhan Reena , Rolania Krishna , Ahlawat Sushil , Gilpin Amy-Marie
Published: March 2023

A field study was conducted to compare the efficacy of 10 recommended insecticides against Earias spp. on okra. Three okra plots (3 m × 5 m (15 m2)) were subjected to each of the 10 insecticidal sprays applied twice at an interval of 10 days. On the third, seventh, and tenth day after each spray, percent shoot and fruit infestation and yield were calculated. All insecticides significantly reduced shoot and fruit infestation compared to the control. However, chlorantraniliprole 18.5%SC was the most effective across all time points and resulted in the highest yield. A second field study, to determine the time till the maximum residue limit (MRL—0.3 mg/kg) and the limit of quantification (LOQ—0.01 mg/kg) for both fruit and soil exposed to either the recommended (125 mL/ha) or a double strength dose (250 mL/ha) of chlorantraniliprole 18.5% SC was undertaken. MRL was reached on the same day following both doses. The LOQ was reached on the seventh and tenth day at recommended and a double strength dose, respectively. Chlorantraniliprole 18.5% SC provides effective control. However, Earias spp. resistance has been observed in other crops. Thus, constant monitoring in the field is needed to ensure its effectiveness.
Juggling during Lockdown: Balancing Telework and Family Life in Pandemic Times and Its Perceived Consequences for the Health and Wellbeing of Working Women
Authors: Loezar-Hernández Mariana , Briones-Vozmediano Erica , Ronda-Pérez Elena , Otero-García Laura
Published: March 2023

The COVID-19 pandemic disrupted work-family balance due to lockdown measures. The aim of this study was to explore the experiences of working mothers in Spain and the consequences of trying to balance work and family for their health and wellbeing. We conducted a qualitative study based on 18 semi-structured interviews with mothers of children under 10. Five themes were identified: (1) Telework—characteristics and challenges of a new labor scenario; (2) Survival and chaos—inability to work, look after children, and manage a household at the same time; (3) Is co-responsibility a matter of luck?—challenges when sharing housework during lockdown; (4) Breakdown of the care and social support system; and (5) decline in health of women trying to balance work and family life. Mothers who had to balance telework against family life suffered physical, mental, and social effects, such as anxiety, stress, sleep deprivation, and relationship problems. This study suggests that, in situations of crisis, gender inequality increases in the household, and women tend to shift back to traditional gendered roles. Governments and employers should be made aware of this, and public policies should be implemented to facilitate work-family reconciliation and co-responsibility within couples
Strategic Team Science Promotes Collaboration and Practice-Based Research at the Research Centers in Minority Institutions
Authors: Levites Strekalova Yulia A. , Kornetti Diana L. , Pemu Priscilla , King Gordon Tandeca , Kumar Deepak , Brown Michelle , Spires Shelley , Ofili Elizabeth O.
Published: March 2023

Background. This paper reports on the implementation and evaluation of a strategy to promote collaborations and team science among investigators at the Research Centers in Minority Institutions (RCMI). The strategy presented in this paper was a hands-on workshop that allowed the application of strategic team science through structured dialogue, asset sharing, and systematic exploration of opportunities for collaboration. Methods. The workshop was attended by more than 100 participants, including RCMI and non-RCMI investigators, practice-based research network (PBRN) supplement program directors, and an NIH Institute on Minority Health and Health Disparities Program Officer. Results. A post-workshop survey was administered to collect participant feedback, assess the relevance of the workshop to the participants’ professional development goals, and gauge the applicability of the tool as a support strategy to promote collaborative research. Most of the participants acknowledged that the session met the conference objectives (95.8%), and 93.7% noted that the workshop, to a high degree, met their personal goals and objectives. During the workshop, participants shared 35 resources they were willing and able to offer for prospective collaborative projects. Conclusion. The experience reported and evaluated in this paper paves the way to understanding methods for disseminating effective strategies for inter-institutional collaborations for the sustainable growth and operation of PBRNs.
Research on the Heterogeneity Threshold Effect of Foreign Direct Investment and Corporate Social Responsibility on Haze Pollution
Authors: Wang Zhanjie , Ma Yongfeng , Wang Shasha , Wang Yongjian
Published: March 2023

Carrying out environmental protection and governance in the process of using foreign capital to develop the economy is a realistic problem that China needs to solve urgently. In order to reduce environmental pollution, all enterprises are called upon by the local government to fulfil CSR and improve the quality of FDI use. However, previous studies have rarely explored the threshold effect of FDI and CSR on haze pollution. This paper employs the threshold effect model to explore the above problem based on panel data of 30 provinces in China from 2009 to 2018. The empirical study found the following: (1) FDI has a significantly positive double-threshold effect on haze pollution. Meanwhile, the promotion effect of FDI on haze pollution is the strongest in the two threshold ranges. (2) CSR has a significantly negative single-threshold effect on haze pollution; that is, the increase in CSR intensity inhibits haze pollution. Such a negative effect shows the characteristics of increasing marginal efficiency. (3) In addition, the provinces in different thresholds display obvious geographical distribution characteristics. Through the above analysis, it can be observed that FDI and CSR have distinct impacts on haze pollution. Thus, the country and the government can reduce haze pollution by improving the investment structure, using environmentally friendly technology, guiding enterprises to abide by business ethics and promoting social responsibilities fulfilment.
Enzymatic Treatments for Biosolids: An Outlook and Recent Trends
Authors: Quintero-García Omar J. , Pérez-Soler Heilyn , Amezcua-Allieri Myriam A.
Published: March 2023

Wastewaters are nutrient-rich organic materials containing significant concentrations of different nutrients, dissolved and particulate matter, microorganisms, solids, heavy metals, and organic pollutants, including aromatic xenobiotics. This variety makes wastewater treatment a technological challenge. As a result of wastewater treatment, biosolids are generated. Biosolids, commonly called sewage sludge, result from treating and processing wastewater residuals. Increased biosolids, or activated sludge, from wastewater treatment is a major environmental and social problem. Therefore, sustainable and energy-efficient wastewater treatment systems must address the water crisis and environmental deterioration. Although research on wastewater has received increasing attention worldwide, the significance of biosolids treatments and valorization is still poorly understood in terms of obtaining value-added products. Hence, in this review, we established some leading technologies (physical, chemical, and biological) for biosolids pretreatment. Later, the research focuses on natural treatment by fungal enzymes to end with lignocellulosic materials and xenobiotic compounds (polyaromatic hydrocarbons) as a carbon source to obtain biobased chemicals. Finally, this review discussed some recent trends and promising renewable resources within the biorefinery approach for bio-waste conversion to value-added by-products.
Pacing Strategy Models in 1500 m Male Freestyle Long-Course Swimming on the Basis of the All-Time Ranking
Authors: Hołub Maciej , Prajzner Arkadiusz , Stanula Arkadiusz
Published: March 2023

In long-distance swimming competitions, a pacing strategy is of considerable importance for the final result and for sporting success. The paper presents the pacing strategy models of the all-time best competitors in 1500 m male freestyle long-course swimming. The top 60 scores were retrieved from official websites. The results were divided into six groups of ten swim times each, with splits of 15 × 100, 5 × 300, 3 × 500, and 2 × 750 m, and then analysis of variance was used. The main effects of the competitor group order revealed with the analysis of variance were statistically significant (p < 0.001). The group effect size turned out very high (ηp2 = 0.95). Consecutive groups of competitors achieved significantly slower results. The magnitude of the interaction effects of the competitor group order and distance splits was moderate (ηp2 of 0.05–0.09) and statistically not significant. The main effects of the 3 × 500, 5 × 300, and 15 × 100 m splits were high and very high (ηp2 of 0.33–0.75) and statistically significant (p < 0.001). The difference between the 2 × 750 m split was statistically not significant. The achieved values of the main effects led to the following trend. In the distance split, the first and last sections did not significantly differ from each other, nor did the middle sections. However, when the middle sections and the first and last sections were compared against each other, a significant discrepancy was observed. The pacing strategies of the best athletes in the history of the competition follow a very similar parabolic trend.
Data-Driven Eco-Efficiency Analysis and Improvement in the Logistics Industry in Anhui
Authors: Sun Shiqiang , Liu Yujia
Published: March 2023

The ecological efficiency (eco-efficiency) of a regional logistics industry (RLI) is widely regarded as a key factor affecting sustainability of economic development, environmental protection, and resources utilization. This study applied a data-driven method to evaluate and increase the eco-efficiency of an RLI. Based on RLI-related data, which were converted into proper dimensionless indices, data envelopment analysis (DEA), which assumes that the decision-making units (DMUs) are in the situation of variable returns to scale, the Banker, Charnes, and Cooper (BCC) model, and Malmquist index model were used to assess the eco-efficiency of the RLI from both static and dynamic viewpoints. Then, a Tobit regression model was built to explore the factors that influence eco-efficiency. The effectiveness of this approach was verified by its application to an example from Anhui Province. This study has theoretical and practical value for the assessment and promotion of the ecological eco-efficiency of the RLI. We believe that our approach offers a powerful tool to assist logistics enterprises and local governments in coordinating the relationship between the RLI economy and the ecological environment, facilitating the drive to carbon neutrality.
‘Boat Quarantine’: Lessons Learned from SARS-CoV-2 Prevention and Control Measures in Fishing Communities in Thailand
Authors: Haritavorn Niphattra
Published: March 2023

SARS-CoV-2 posed, and continues to pose, a severe threat to life, and for fishermen in Thailand, specific multifaceted quarantine design measures have been required. In response to the SARS-CoV-2 outbreak in Trat province, a community quarantine centre was designed using boats as quarantine facilities. This study examines the implementation of boat quarantine in response to the SARS-CoV-2 pandemic within the fishermen communities in Trat province, Thailand. In-depth interviews with 45 key individuals who have been involved in the control and prevention of SARS-CoV-2 among fishermen in the fishing communities were subjected to a thematic analysis. Boat quarantine was used to separate and restrict contact between fishermen who were exposed to SARS-CoV-2, to determine whether they became sick and to prevent mass infection within the community. Using a boat as a place to self-isolate has become an effective form of quarantine for fishermen. This model has implications for the future of infectious disease control onshore, both while the pandemic continues and after the pandemic comes to an end.
Candida Species in Children Undergoing Orthodontic Treatment with Removable Appliances: A Pilot Study
Authors: Brzezińska-Zając Aleksandra , Sycińska-Dziarnowska Magdalena , Spagnuolo Gianrico , Szyszka-Sommerfeld Liliana , Woźniak Krzysztof
Published: March 2023

The purpose of this study was to analyze the effect of orthodontic treatment with removable appliances on the growth of Candida spp. in children undergoing orthodontic treatment. The study included 60 patients of equal numbers as to gender from the orthodontics department of the Pomeranian Medical University in Szczecin, Poland. All patients were aged 6–12 years and were qualified for orthodontic treatment with removable appliances. The following examinations were performed on the day of treatment initiation (T1) and 6 months after the start of treatment (T2); a collection of oral swabs for culture on Sabouraud’s medium and the identification of fungal colonies using the VITEK®2 YST. At T1, 42 (70%) subjects, were free of Candida, while after 6 months of treatment, the number decreased to 25 (41.67%). Two types of fungi, C. albicans and C. parapsilosis, predominated in the test performed at T1. The study at T2 showed that C. albicans most frequently colonized the oral cavity in 23 children (38.33%). Three new strains C. dubliniensis, C. kefyr, and C. krusei were identified at T2. Statistical analysis showed a significant correlation between the culture results and the age of the patient at T2. Patients older than 9 years had significantly more positive tests. Orthodontic treatment with removable appliances contributes to increased oral colonization by Candida spp.
The Impact of Household Migration on the Intergenerational Educational Mobility: Based on the Perspective of Adolescent Development
Authors: Zhou Xiaohe , Cheng Mingda , Ye Chunhui
Published: March 2023

Improving intergenerational mobility is crucial for enhancing the efficacy of human capital, ensuring social vitality, and supporting sustainable long-term economic growth. Based on the China Labor-force Dynamic Survey (CLDS) of 2014, this paper empirically examines the effect of adolescent household migration on intergenerational educational mobility by using a fixed-effect model. The study found that: (1) Household migration in the adolescent period significantly improves intergenerational educational mobility. (2) The quality and quantity of education of offspring are the channels through which household migration improves the intergenerational educational mobility of the household. (3) There are significant differences between urban and rural areas, gender, and household resource allocation in the effect of adolescent household migration on intergenerational educational mobility. As the majority of poor households are unable to improve intergenerational mobility through migration due to its costs and institutional barriers, this paper suggests that the government should concentrate on reducing regional disparities in educational resources, advancing rural education reform, and enhancing social security.
App-Delivered Mindfulness Training to Reduce Anxiety in People with HIV Who Smoke: A One-Armed Feasibility Trial
Authors: Cioe Patricia , Sokolovsky Alexander , Brewer Judson , Kahler Christopher
Published: March 2023

Introduction: People with HIV (PWH) who smoke have reported that managing anxiety is a barrier to making a quit attempt and maintaining abstinence post-quit. This study examined the feasibility and acceptability of an app-based mindfulness intervention, Unwinding Anxiety, to reduce anxiety prior to a quit attempt in PWH who were not planning to quit in the next 30 days. Methods: Sixteen PWH (mean age 51.5 [SD = 13.2]; mean cigarettes per day 11.4 [SD = 5.4]) were enrolled and followed for eight weeks. A smartphone-based app with 30 modules designed to reduce anxiety was introduced at baseline; participants were encouraged to complete one module daily for four weeks. Symptoms of anxiety and readiness to quit smoking were measured at baseline and weeks 4 and 8. The mean number of modules completed, session attendance, and number of study completers were examined. Generalized estimating equations (GEE) were used to examine changes in self-reported anxiety and readiness to quit at baseline, week 4, and week 8. A brief qualitative interview was conducted at week 4 to explore the acceptability of the app. Results: Feasibility was high, with 93% of participants completing the study. The mean number of study sessions completed was 2.7 (SD = 0.59), and the mean number of modules completed was 16.0 (SD 16.8). Anxiety was high at baseline (M = 14.4, SD = 3.9), but lower at week 4 (b = −5.5; CI: [−9.4, −1.7]; p = 0.004) and week 8 (b = −5.1; CI: [−8.8, −1.3]; p = 0.008), and stable between weeks 4 and 8 (b = 0.48; CI: [−2.0, 3.0]; p = 0.706). Readiness to quit significantly increased from baseline M = 5.5 (SD = 1.6) to week 4 (b = 0.56; CI: [0.20, 0.91]; p = 0.002) but was not significantly different from baseline at week 8 (b = 0.34; CI: [−0.30, 1.0]; p = 0.30). Ad-hoc moderation analyses found that anxiety had a small significantly positive association with readiness to quit at baseline (main effect: b = 0.10; SE = 0.03; p < 0.001) and significantly attenuated the increase in readiness to quit observed at week 4 (anxiety by week 4 interaction: b = −0.08; SE = 0.03; p = 0.009). Conclusions: App-based mindfulness training appears to be feasible and acceptable for PWH who smoke and report baseline anxiety. At week 4, anxiety was reduced and readiness to quit was increased, perhaps a key time point for a smoking cessation attempt.
Long-Term Evaluation of Retinal Morphology and Function in Rosa26-Cas9 Knock-In Mice
Authors: Mohan Kabhilan , Dubey Sushil Kumar , Jung Kyungsik , Dubey Rashmi , Wang Qing Jun , Prajapati Subhash , Roney Jacob , Abney Jennifer , Kleinman Mark Ellsworth
Published: March 2023

The CRISPR/Cas9 system is a robust, efficient, and cost-effective gene editing tool widely adopted in translational studies of ocular diseases. However, in vivo CRISPR-based editing in animal models poses challenges such as the efficient delivery of the CRISPR components in viral vectors with limited packaging capacity and a Cas9-associated immune response. Using a germline Cas9-expressing mouse model would help to overcome these limitations. Here, we evaluated the long-term effects of SpCas9 expression on retinal morphology and function using Rosa26-Cas9 knock-in mice. We observed abundant SpCas9 expression in the RPE and retina of Rosa26-Cas9 mice using the real-time polymerase chain reaction (RT-PCR), Western blotting, and immunostaining. SD-OCT imaging and histological analysis of the RPE, retinal layers, and vasculature showed no apparent structural abnormalities in adult and aged Cas9 mice. Full-field electroretinogram of adult and aged Cas9 mice showed no long-term functional changes in the retinal tissues because of constitutive Cas9 expression. The current study showed that both the retina and RPE maintain their phenotypic and functional features in Cas9 knock-in mice, establishing this as an ideal animal model for developing therapeutics for retinal diseases.
Dual Inoculation with Rhizophagus irregularis and Bacillus megaterium Improves Maize Tolerance to Combined Drought and High Temperature Stress by Enhancing Root Hydraulics, Photosynthesis and Hormonal Responses
Authors: Romero-Munar Antonia , Aroca Ricardo , Zamarreño Angel María , García-Mina José María , Perez-Hernández Noelia , Ruiz-Lozano Juan Manuel
Published: March 2023

Climate change is leading to combined drought and high temperature stress in many areas, drastically reducing crop production, especially for high-water-consuming crops such as maize. This study aimed to determine how the co-inoculation of an arbuscular mycorrhizal (AM) fungus (Rhizophagus irregularis) and the PGPR Bacillus megaterium (Bm) alters the radial water movement and physiology in maize plants in order to cope with combined drought and high temperature stress. Thus, maize plants were kept uninoculated or inoculated with R. irregularis (AM), with B. megaterium (Bm) or with both microorganisms (AM + Bm) and subjected or not to combined drought and high temperature stress (D + T). We measured plant physiological responses, root hydraulic parameters, aquaporin gene expression and protein abundances and sap hormonal content. The results showed that dual AM + Bm inoculation was more effective against combined D + T stress than single inoculation. This was related to a synergistic enhancement of efficiency of the phytosystem II, stomatal conductance and photosynthetic activity. Moreover, dually inoculated plants maintained higher root hydraulic conductivity, which was related to regulation of the aquaporins ZmPIP1;3, ZmTIP1.1, ZmPIP2;2 and GintAQPF1 and levels of plant sap hormones. This study demonstrates the usefulness of combining beneficial soil microorganisms to improve crop productivity under the current climate-change scenario.
CFTR Modulators Rescue the Activity of CFTR in Colonoids Expressing the Complex Allele p.[R74W;V201M;D1270N]/dele22_24
Authors: Kleinfelder Karina , Somenza Elena , Farinazzo Alessia , Conti Jessica , Lotti Virginia , Latorre Roberta Valeria , Rodella Luca , Massella Arianna , Tomba Francesco , Bertini Marina , Sorio Claudio , Melotti Paola
Published: March 2023

An Italian, 46-year-old female patient carrying the complex allele p.[R74W;V201M;D1270N] in trans with CFTR dele22_24 was diagnosed at the Cystic Fibrosis (CF) Center of Verona as being affected by CF-pancreatic sufficient (CF-PS) in 2021. The variant V201M has unknown significance, while both of the other variants of this complex allele have variable clinical consequences, according to the CFTR2 database, with reported clinical benefits for treatment with ivacaftor + tezacaftor and ivacaftor + tezacaftor + elexacaftor in patients carrying the R74W-D1270N complex allele, which are currently approved (in USA, not yet in Italy). She was previously followed up by pneumologists in northern Italy because of frequent bronchitis, hemoptysis, recurrent rhinitis, Pseudomonas aeruginosa lung colonization, bronchiectasis/atelectasis, bronchial arterial embolization and moderately compromised lung function (FEV1: 62%). Following a sweat test with borderline results, she was referred to the Verona CF Center where she presented abnormal values in both optical beta-adrenergic sweat tests and intestinal current measurement (ICM). These results were consistent with a diagnosis of CF. CFTR function analyses were also performed in vitro by forskolin-induced swelling (FIS) assay and short-circuit currents (Isc) in the monolayers of the rectal organoids. Both of these assays showed significantly increased CFTR activity following treatment with the CFTR modulators. Western-blot analysis revealed increased fully glycosylated CFTR protein after treatment with correctors, in line with the functional analysis. Interestingly, tezacaftor, together with elexacaftor, rescued the total organoid area under steady-state conditions, even in the absence of the CFTR agonist forskolin. In conclusion, in ex vivo and in vitro assays, we measured a residual function that was significantly enhanced by in vitro incubation with CFTR modulators, especially by ivacaftor + tezacaftor + elexacaftor, suggesting this combination as a potentially optimal treatment for this case.
Tuberculosis: Pathogenesis, Current Treatment Regimens and New Drug Targets
Authors: Alsayed Shahinda S. R. , Gunosewoyo Hendra
Published: March 2023

Mycobacterium tuberculosis (M. tb), the causative agent of TB, is a recalcitrant pathogen that is rife around the world, latently infecting approximately a quarter of the worldwide population. The asymptomatic status of the dormant bacteria escalates to the transmissible, active form when the host’s immune system becomes debilitated. The current front-line treatment regimen for drug-sensitive (DS) M. tb strains is a 6-month protocol involving four different drugs that requires stringent adherence to avoid relapse and resistance. Poverty, difficulty to access proper treatment, and lack of patient compliance contributed to the emergence of more sinister drug-resistant (DR) strains, which demand a longer duration of treatment with more toxic and more expensive drugs compared to the first-line regimen. Only three new drugs, bedaquiline (BDQ) and the two nitroimidazole derivatives delamanid (DLM) and pretomanid (PMD) were approved in the last decade for treatment of TB—the first anti-TB drugs with novel mode of actions to be introduced to the market in more than 50 years—reflecting the attrition rates in the development and approval of new anti-TB drugs. Herein, we will discuss the M. tb pathogenesis, current treatment protocols and challenges to the TB control efforts. This review also aims to highlight several small molecules that have recently been identified as promising preclinical and clinical anti-TB drug candidates that inhibit new protein targets in M. tb.
Defining the Emergence of New Immunotherapy Approaches in Breast Cancer: Role of Myeloid-Derived Suppressor Cells
Authors: Sánchez-León María Luisa , Jiménez-Cortegana Carlos , Silva Romeiro Silvia , Garnacho Carmen , de la Cruz-Merino Luis , García-Domínguez Daniel J. , Hontecillas-Prieto Lourdes , Sánchez-Margalet Víctor
Published: March 2023

Breast cancer (BC) continues to be the most diagnosed tumor in women and a very heterogeneous disease both inter- and intratumoral, mainly given by the variety of molecular profiles with different biological and clinical characteristics. Despite the advancements in early detection and therapeutic strategies, the survival rate is low in patients who develop metastatic disease. Therefore, it is mandatory to explore new approaches to achieve better responses. In this regard, immunotherapy arose as a promising alternative to conventional treatments due to its ability to modulate the immune system, which may play a dual role in this disease since the relationship between the immune system and BC cells depends on several factors: the tumor histology and size, as well as the involvement of lymph nodes, immune cells, and molecules that are part of the tumor microenvironment. Particularly, myeloid-derived suppressor cell (MDSC) expansion is one of the major immunosuppressive mechanisms used by breast tumors since it has been associated with worse clinical stage, metastatic burden, and poor efficacy of immunotherapies. This review focuses on the new immunotherapies in BC in the last five years. Additionally, the role of MDSC as a therapeutic target in breast cancer will be described.
Genetic Background of Metabolically Healthy and Unhealthy Obesity Phenotypes in Hungarian Adult Sample Population
Authors: Piko Peter , Llanaj Erand , Nagy Karoly , Adany Roza
Published: March 2023

A specific phenotypic variant of obesity is metabolically healthy (MHO), which is characterized by normal blood pressure and lipid and glucose profiles, in contrast to the metabolically unhealthy variant (MUO). The genetic causes underlying the differences between these phenotypes are not yet clear. This study aims to explore the differences between MHO and MUO and the contribution of genetic factors (single nucleotide polymorphisms—SNPs) in 398 Hungarian adults (81 MHO and 317 MUO). For this investigation, an optimized genetic risk score (oGRS) was calculated using 67 SNPs (related to obesity and to lipid and glucose metabolism). Nineteen SNPs were identified whose combined effect was strongly associated with an increased risk of MUO (OR = 1.77, p < 0.001). Four of them (rs10838687 in MADD, rs693 in APOB, rs1111875 in HHEX, and rs2000813 in LIPG) significantly increased the risk of MUO (OR = 1.76, p < 0.001). Genetic risk groups based on oGRS were significantly associated with the risk of developing MUO at a younger age. We have identified a cluster of SNPs that contribute to the development of the metabolically unhealthy phenotype among Hungarian adults suffering from obesity. Our findings emphasize the significance of considering the combined effect(s) of multiple genes and SNPs in ascertaining cardiometabolic risk in obesity in future genetic screening programs.
A Proof of Principle Proteomic Study Detects Dystrophin in Human Plasma: Implications in DMD Diagnosis and Clinical Monitoring
Authors: Rossi Rachele , Johansson Camilla , Heywood Wendy , Vinette Heloise , Jensen Gabriella , Tegel Hanna , Jiménez-Requena Albert , Torelli Silvia , Al-Khalili Szigyarto Cristina , Ferlini Alessandra
Published: March 2023

Duchenne muscular dystrophy (DMD) is a rare neuromuscular disease caused by pathogenic variations in the DMD gene. There is a need for robust DMD biomarkers for diagnostic screening and to aid therapy monitoring. Creatine kinase, to date, is the only routinely used blood biomarker for DMD, although it lacks specificity and does not correlate with disease severity. To fill this critical gap, we present here novel data about dystrophin protein fragments detected in human plasma by a suspension bead immunoassay using two validated anti-dystrophin-specific antibodies. Using both antibodies, a reduction of the dystrophin signal is detected in a small cohort of plasma samples from DMD patients when compared to healthy controls, female carriers, and other neuromuscular diseases. We also demonstrate the detection of dystrophin protein by an antibody-independent method using targeted liquid chromatography mass spectrometry. This last assay detects three different dystrophin peptides in all healthy individuals analysed and supports our finding that dystrophin protein is detectable in plasma. The results of our proof-of-concept study encourage further studies in larger sample cohorts to investigate the value of dystrophin protein as a low invasive blood biomarker for diagnostic screening and clinical monitoring of DMD.
Coumarin-Based Compounds as Inhibitors of Tyrosinase/Tyrosine Hydroxylase: Synthesis, Kinetic Studies, and In Silico Approaches
Authors: Nunes Jéssica Alves , Araújo Rodrigo Santos Aquino de , Silva Fabrícia Nunes da , Cytarska Joanna , Łączkowski Krzysztof Z. , Cardoso Sílvia Helena , Mendonça-Júnior Francisco Jaime Bezerra , Silva-Júnior Edeildo Ferreira da
Published: March 2023

Cancer represents the main cause of morbidity and mortality worldwide, constituting a serious health problem. In this context, melanoma represents the most aggressive and fatal type of skin cancer, with death rates increasing every year. Scientific efforts have been addressed to the development of inhibitors targeting the tyrosinase enzyme as potential anti-melanoma agents due to the importance of this enzyme in melanogenesis biosynthesis. Coumarin-based compounds have shown potential activity as anti-melanoma agents and tyrosinase inhibitors. In this study, coumarin-based derivatives were designed, synthesized, and experimentally evaluated upon tyrosinase. Compound FN-19, a coumarin–thiosemicarbazone analog, exhibited potent anti-tyrosinase activity, with an IC50 value of 42.16 ± 5.16 µM, being more active than ascorbic acid and kojic acid, both reference inhibitors. The kinetic study showed that FN-19 acts as a mixed inhibitor. Still, for this compound, molecular dynamics (MD) simulations were performed to determine the stability of the complex with tyrosinase, generating RMSD, RMSF, and interaction plots. Additionally, docking studies were performed to elucidate the binding pose at the tyrosinase, suggesting that the hydroxyl group of coumarin derivative performs coordinate bonds (bidentate) with the copper(II) ions at distances ranging from 2.09 to 2.61 Å. Then, MM/PBSA calculations revealed that van der Waals interactions are the most relevant intermolecular forces for complex stabilization. Furthermore, it was observed that FN-19 has a binding energy (ΔEMM) value similar to tropolone, a tyrosinase inhibitor. Therefore, the data obtained in this study will be useful for designing and developing novel coumarin-based analogs targeting the tyrosinase enzyme.
Biology and Regulation of Staphylococcal Biofilm
Authors: François Patrice , Schrenzel Jacques , Götz Friedrich
Published: March 2023

Despite continuing progress in medical and surgical procedures, staphylococci remain the major Gram-positive bacterial pathogens that cause a wide spectrum of diseases, especially in patients requiring the utilization of indwelling catheters and prosthetic devices implanted temporarily or for prolonged periods of time. Within the genus, if Staphylococcus aureus and S. epidermidis are prevalent species responsible for infections, several coagulase-negative species which are normal components of our microflora also constitute opportunistic pathogens that are able to infect patients. In such a clinical context, staphylococci producing biofilms show an increased resistance to antimicrobials and host immune defenses. Although the biochemical composition of the biofilm matrix has been extensively studied, the regulation of biofilm formation and the factors contributing to its stability and release are currently still being discovered. This review presents and discusses the composition and some regulation elements of biofilm development and describes its clinical importance. Finally, we summarize the numerous and various recent studies that address attempts to destroy an already-formed biofilm within the clinical context as a potential therapeutic strategy to avoid the removal of infected implant material, a critical event for patient convenience and health care costs.
Emerging Roles of Endocannabinoids as Key Lipid Mediators for a Successful Pregnancy
Authors: Rava Alessandro , Trezza Viviana
Published: March 2023

In recent years, Cannabis use/misuse for treating pregnancy-related symptoms and other chronic conditions has increased among pregnant women, favored by decriminalization and/or legalization of its recreational uses in addition to its easy accessibility. However, there is evidence that prenatal Cannabis exposure might have adverse consequences on pregnancy progression and a deleterious impact on proper neurodevelopmental trajectories in the offspring. Maternal Cannabis use could interfere with the complex and finely controlled role performed by the endocannabinoid system in reproductive physiology, impairing multiple gestational processes from blastocyst implantation to parturition, with long-lasting intergenerational effects. In this review, we discuss current clinical and preclinical evidence regarding the role of endocannabinoids in development, function, and immunity of the maternal–fetal interface, focusing on the impact of Cannabis constituents on each of these gestational processes. We also discuss the intrinsic limitations of the available studies and the future perspectives in this challenging research field.
The Phaseolus vulgaris Receptor-Like Kinase PvFER1 and the Small Peptides PvRALF1 and PvRALF6 Regulate Nodule Number as a Function of Nitrate Availability
Authors: Solís-Miranda Jorge , Juárez-Verdayes Marco A. , Nava Noreide , Rosas Paul , Leija-Salas Alfonso , Cárdenas Luis , Quinto Carmen
Published: March 2023

Legumes associate with Gram-negative soil bacteria called rhizobia, resulting in the formation of a nitrogen-fixing organ, the nodule. Nodules are an important sink for photosynthates for legumes, so these plants have developed a systemic regulation mechanism that controls their optimal number of nodules, the so-called autoregulation of nodulation (AON) pathway, to balance energy costs with the benefits of nitrogen fixation. In addition, soil nitrate inhibits nodulation in a dose-dependent manner, through systemic and local mechanisms. The CLE family of peptides and their receptors are key to tightly controlling these inhibitory responses. In the present study, a functional analysis revealed that PvFER1, PvRALF1, and PvRALF6 act as positive regulators of the nodule number in growth medium containing 0 mM of nitrate but as negative regulators in medium with 2 and 5 mM of nitrate. Furthermore, the effect on nodule number was found to be consistent with changes in the expression levels of genes associated with the AON pathway and with the nitrate-mediated regulation of nodulation (NRN). Collectively, these data suggest that PvFER1, PvRALF1, and PvRALF6 regulate the optimal number of nodules as a function of nitrate availability.
Evaluation of Polymeric Particles for Modular Tissue Cultures in Developmental Engineering
Authors: Xiang Yu , Yan Jiongyi , Bao Xujin , Gleadall Andrew , Roach Paul , Sun Tao
Published: March 2023

Developmental engineering (DE) aims to culture mammalian cells on corresponding modular scaffolds (scale: micron to millimeter), then assemble these into functional tissues imitating natural developmental biology processes. This research intended to investigate the influences of polymeric particles on modular tissue cultures. When poly(methyl methacrylate) (PMMA), poly(lactic acid) (PLA) and polystyrene (PS) particles (diameter: 5–100 µm) were fabricated and submerged in culture medium in tissue culture plastics (TCPs) for modular tissue cultures, the majority of adjacent PMMA, some PLA but no PS particles aggregated. Human dermal fibroblasts (HDFs) could be directly seeded onto large (diameter: 30–100 µm) PMMA particles, but not small (diameter: 5–20 µm) PMMA, nor all the PLA and PS particles. During tissue cultures, HDFs migrated from the TCPs surfaces onto all the particles, while the clustered PMMA or PLA particles were colonized by HDFs into modular tissues with varying sizes. Further comparisons revealed that HDFs utilized the same cell bridging and stacking strategies to colonize single or clustered polymeric particles, and the finely controlled open pores, corners and gaps on 3D-printed PLA discs. These observed cell–scaffold interactions, which were then used to evaluate the adaptation of microcarrier-based cell expansion technologies for modular tissue manufacturing in DE.
New Insights into the Modification of the Non-Core Metabolic Pathway of Steroids in Mycolicibacterium and the Application of Fermentation Biotechnology in C-19 Steroid Production
Authors: Zhang Yang , Xiao Peiyao , Pan Delong , Zhou Xiuling
Published: March 2023

Androsta-4-ene-3,17-dione (AD), androsta-1,4-diene-3,17-dione (ADD), and 9α-hydroxy-4-androstene-3,17-dione (9-OHAD), which belong to C-19 steroids, are critical steroid-based drug intermediates. The biotransformation of phytosterols into C-19 steroids by Mycolicibacterium cell factories is the core step in the synthesis of steroid-based drugs. The production performance of engineered mycolicibacterial strains has been effectively enhanced by sterol core metabolic modification. In recent years, research on the non-core metabolic pathway of steroids (NCMS) in mycolicibacterial strains has made significant progress. This review discusses the molecular mechanisms and metabolic modifications of NCMS for accelerating sterol uptake, regulating coenzyme I balance, promoting propionyl-CoA metabolism, reducing reactive oxygen species, and regulating energy metabolism. In addition, the recent applications of biotechnology in steroid intermediate production are summarized and compared, and the future development trend of NCMS research is discussed. This review provides powerful theoretical support for metabolic regulation in the biotransformation of phytosterols.