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The assignment of the hydrogen bonded O–H stretch vibration in the proline matrix IR spectrum has sparked controversy. Employing constrained nuclear electronic orbital methods, we provide a clear assignment that the vibrational frequency drops to near 3000 cm−1 as a result of the interplay between electronic effects, nuclear quantum effects, and matrix effects. [ABSTRACT FROM AUTHOR]

Fibrolamellar carcinoma (FLC) is a rare, lethal, early-onset liver cancer with a critical need for new therapeutics. The primary driver in FLC is the fusion oncoprotein, DNAJ-PKAc, which remains challenging to target therapeutically. It is critical, therefore, to expand understanding of the FLC molecular landscape to identify druggable pathways/targets. Here, we perform the most comprehensive integrative proteo-metabolomic analysis of FLC. We also conduct nutrient manipulation, respirometry analyses, as well as key loss-of-function assays in FLC tumor tissue slices from patients. We propose a model of cellular energetics in FLC pointing to proline anabolism being mediated by ornithine aminotransferase hyperactivity and ornithine transcarbamylase hypoactivity with serine and glutamine catabolism fueling the process. We highlight FLCs potential dependency on voltage-dependent anion channel (VDAC), a mitochondrial gatekeeper for anions including pyruvate. The metabolic rewiring in FLC that we propose in our model, with an emphasis on mitochondria, can be exploited for therapeutic vulnerabilities.

Paritaprevir is an orally bioavailable, macrocyclic drug used for treating chronic Hepatitis C virus (HCV) infection. Its structures have been elusive to the public until recently when one of the crystal forms is solved by microcrystal electron diffraction (MicroED). In this work, the MicroED structures of two distinct polymorphic crystal forms of paritaprevir are reported from the same experiment. The different polymorphs show conformational changes in the macrocyclic core, as well as the cyclopropyl sulfonamide and methyl pyrazinamide substituents. Molecular docking shows that one of the conformations fits well into the active site pocket of the HCV non-structural 3/4A (NS3/4A) serine protease target, and can interact with the pocket and catalytic triad via hydrophobic interactions and hydrogen bonds. These results can provide further insight for optimization of the binding of acyl sulfonamide inhibitors to the HCV NS3/4A serine protease. In addition, this also demonstrates the opportunity to derive different polymorphs and distinct macrocycle conformations from the same experiments using MicroED.

A clear understanding of real-world uptake of nirmatrelvir-ritonavir for treatment of SARS-CoV-2 can inform treatment allocation strategies and improve interpretation of effectiveness studies. We used data from a large US healthcare system to describe nirmatrelvir-ritonavir dispenses among all SARS-CoV-2 positive patients aged ≥ 12 years meeting recommended National Institutes of Health treatment eligibility criteria for the study period between 1 January and 31 December, 2022. Overall, 10.9% (N = 34,791/319,900) of treatment eligible patients with SARS-CoV-2 infections received nirmatrelvir-ritonavir over the study period. Although uptake of nirmatrelvir-ritonavir increased over time, by the end of 2022, less than a quarter of treatment eligible patients with SARS-CoV-2 infections had received nirmatrelvir-ritonavir. Across patient demographics, treatment was generally consistent with tiered treatment guidelines, with dispenses concentrated among patients aged ≥ 65 years (14,706/63,921; 23.0%), and with multiple comorbidities (10,989/54,431; 20.1%). However, neighborhoods of lower socioeconomic status (upper third of neighborhood deprivation index [NDI]) had between 12% (95% CI: 7-18%) and 28% (25-32%) lower odds of treatment dispense over the time periods studied compared to the lower third of NDI distribution, even after accounting for demographic and clinical characteristics. A limited chart review (N = 40) confirmed that in some cases a decision not to treat was appropriate and aligned with national guidelines to use clinical judgement on a case-by-case basis. There is a need to enhance patient and provider awareness on the availability and benefits of nirmatrelvir-ritonavir for the treatment of COVID-19 illness.

OBJECTIVES: Although guidelines recommend antiviral therapy for outpatients with COVID-19 who are at high risk of progressing to severe conditions, such as older adults, many patients do not receive appropriate treatment. Little is known, however, about the physician factors associated with the prescription of guideline-recommended antiviral therapy for patients with COVID-19. DESIGN: A cross-sectional study. SETTING: Data including outpatient visits in primary care clinics in Japan from April to August 2023. PARTICIPANTS: We analysed 30 953 outpatients aged ≥65 years treated with COVID-19 (mean (SD) age, 75.0 (7.6) years; 17 652 women (57.0%)) in 1394 primary care clinics. OUTCOME MEASURES: The primary outcome was the prescription of guideline-recommended antivirals (ie, nirmatrelvir-ritonavir or molnupiravir), adjusted for patient characteristics, months of visits and regions. RESULTS: Antiviral prescriptions were concentrated among a small proportion of physicians; for example, the top 10% of physicians that had the largest number of nirmatrelvir-ritonavir prescriptions accounted for 92.4% of all nirmatrelvir-ritonavir prescriptions. After adjusting for potential confounders, physicians with higher patient volumes were more likely to prescribe guideline-recommended antivirals to their patients (adjusted OR (aOR) for high vs low volume, 1.76; 95% CI 1.31 to 2.38; adjusted p

Background: Salinity is a major threat to rice growth and productivity. Utilizing wild rice-derived genes and biostimulants with high growth promoting- and stress-alleviating potential can significantly improve salinity tolerance in cultivated rice. Herein, we investigated the vegetative growth and physiological responses of Giza 177 (Oryza sativa, salinity sensitive, high-yielding cultivar) and a promising introgression salt tolerant line (sativa/glaberrima; SG 65) from a population of Giza 177 × African rice (Oryza glaberrima) under low (2.75 mS/cm) and high (5.5 mS/cm) salinity stress. The possible ameliorative effects of priming rice seeds in moringa leaf extract (MLE) on these responses were also tested. Results: The two salinity levels induced differential reduction in plant growth in both cultivars. In the MLE-unprimed plants, salinity induced 34–54% and 30–45% reductions in biomass accumulation in Giza 177 and SG 65, respectively. These responses were associated with significant differential reductions in relative water content, chlorophylls, carotenoids, and gas exchange parameters (transpiration rate, net photosynthetic rate, stomatal conductance, and intercellular CO2 concentration), ascorbic acid, and total protein. Conversely, salinity induced the accumulation of H2O2, malondialdehyde, proline, carbohydrate fractions, and membrane injury. MLE treatment mitigated the above salinity-induced adverse effects in both cultivars via reducing the salt-induced oxidative stress through the induction of non-enzymic (total phenols, and flavonoids) and enzymic antioxidants including ascorbate peroxidase, catalase, peroxidase, and polyphenol oxidase in both cultivars. SG 65 plants exhibited consistently higher salt tolerance and responsiveness to MLE than Giza 177. Conclusions: This study reports significant differences in an array of critical physiological and biochemical indices that underpin the divergent responses between the two salinized cultivars. It demonstrates the potential of African rice-derived genomic fragments and MLE priming in mitigating salinity stress, highlighting their use as a sustainable strategy for increasing rice production in salt-affected soils. [ABSTRACT FROM AUTHOR]

Unusual amino acids have arisen as an indispensable instrument at the disposal of modern medicinal chemistry. While extensively exploited as building blocks in the search for new pharmaceuticals, their application goes far beyond. They are currently involved in explorations of the structure and conformational mobility of peptides, modification and amplification of peptidomimetic activity, and others. Herein, we report an effective synthetic approach to nonplanar, conformationally restricted, sp 3 -enriched spirocyclic α-prolines. The protocol employs readily available nitrile-based starting materials and conventional experimental procedures. The synthetic sequence is concise and includes three principal stages (one of them a four-step telescopic process). The reactions proceed on a multigram scale affording the target prolines in overall good yields. The possibility of chiral separation of the synthesized racemic spiro prolines to both pure enantiomers is shown. The building blocks synthesized in the study are expected to have practical uses in the field of medicinal chemistry. [ABSTRACT FROM AUTHOR]

In the past decade, there has been increased interest in rapeseed cultivation in Iran due to its role in crop rotation with cereals and its contribution to edible oil production. In this regard, a two-year experiment was conducted to investigate the effect of chitosan application on the yield and physiological traits of rapeseed genotypes under drought stress conditions. The experiment was designed as a factorial split plot with a randomized complete block design (RCBD) and three replications. The main plots included irrigation at two levels, normal irrigation (control) and stopping irrigation after the flowering stage, and chitosan at two levels, foliar spraying with pure water (not using chitosan) and foliar spraying with chitosan at a rate of 250 mg per liter. The subplots included rapeseed genotypes, including BAL104, DIE710/08, BAL101, BAL102, QUIE03/11, and Okapi. Result of the mean comparison of irrigation and genotype interaction on grain yield showed that under normal irrigation conditions, Okapi had the highest grain yield with an average of 6,884 kg/ha. However, when irrigation was stopped after the flowering stage, genotype DIE710/08 had the highest grain yield with an average of 3,261 kg/ha. Furthermore, the Okapi genotype showed a sharp decrease in grain yield under water stress. Results also showed that the application of chitosan treatment caused a significant decrease of erucic acid and glucosinolate (18% and 17%, respectively) under stress conditions compared to the control treatment. The Okapi cultivar thrives best when there are no restrictions on irrigation water. However, it’s recommended to use the DIE710/08 genotype when there is stress during the flowering stage. This genotype can still provide a decent grain yield in these conditions. [ABSTRACT FROM AUTHOR]

L-Proline (l-Pro) is a non-essential amino acid which, in high concentrations, can cause neurological problems including seizures, although the causative mechanism for this is unclear. Here, we studied the impact of physiological levels of proline on brain energy metabolism and investigated the metabolism of l-Pro itself, using the cortical brain tissue slice and stable isotope labelling from [1-13 C]glucose and [1,2-13 C]acetate detected by NMR spectroscopy and LCMS. l-Pro was actively taken up by the slices and significantly reduced the total metabolic pools of all measured metabolites with glutamine the least affected, while reducing net flux of 13C into glycolytic byproducts (lactate and alanine). Conversely, net flux into Krebs cycle intermediates was increased, suggesting that L-Pro at lower concentrations was driving increased mitochondrial activity in both neurons and glia at the expense of glycolysis and metabolic pool sizes. As there was no evidence of metabolism of [1-13 C] l-Pro in slices under normo-glycemic conditions, the effect of proline on metabolism was not due to displacement of metabolites by added l-Pro. Comparison of the metabolic fingerprint generated by l-Pro in slices metabolizing [3-13 C]pyruvate with that generated by ligands active in the GABAergic system suggested that l-Pro may engender effects similar to that of the inhibitory neurotransmitter and metabolite γ-aminobutyric acid (GABA), in line with previous suggestions that l-Pro may be a GABA mimetic in addition to its role as a modulator of mitochondrial metabolism. [ABSTRACT FROM AUTHOR]

Proline is a major substrate in collagen biosynthesis and is required for collagen molecule formations. However, detailed explanations of the molecular basis through which proline functions in collagen biosynthesis have yet to be provided. Thus, genome-wide screening was employed to elucidate these in the pre-osteoblastic MC3T3-E1 and human periodontal ligament fibroblast (hPDLF) cell lines. Indeed, both cell lines represent important sources for collagen biosynthesis and tissue regeneration in the dental region, specifically treating extracellular proline during cultivations. The altered gene expression patterns were identified, and the precise expression patterns were confirmed by microarray. Cell viability and osteogenic differentiation patterns were examined using a range of experimental methods, such as the MTS assay, ALP staining, ARS staining, and collagen (COL)-type1A ELISA. Overall, we revealed a cell line-specific function of exogenous proline in collagen biosynthesis during osteogenic differentiation conditions with the candidate signaling pathways. These putative signaling networks could represent plausible answers to understanding collagen biosynthesis for regenerating connective tissues such as skin, muscle, and bone. [ABSTRACT FROM AUTHOR]

Introduction: The growth of evergreen fruit trees is influenced by the interaction of soil nitrogen (N) and leaf amino acid contents. However, information on free amino acid contents in leaves of fruiting and non-fruiting branches during long-term N fertilizer application remains scarce. Methods: Here, a four-year field experiment (2018-2021) in a citrus orchard revealed consistently lower total N and amino acid contents in leaves of fruiting compared to non-fruiting branches. Results and discussion: Appropriate N fertilizer application increased free amino acid and total N contents in leaves of both types of branches and fruits, but excessive amounts led to decreases. Correlation analysis showed that, in the early stage of fruit development, leaves on both types of branches can meet the N requirements of the fruit (R²=0.77 for fruiting, R²=0.82 for non-fruiting). As fruits entered the swelling stage, a significant positive correlation emerged between fruiting branch leaves and fruit total N content (R²=0.68), while the R² for leaves on non-fruiting branches dropped to 0.47, indicating a shift in N supply towards leaves on fruiting branches. Proline and arginine are the most abundant amino acids in these leaves. At fruit maturity, these amino acids account for more than half of the total amino acids in the fruit (29.0% for proline and 22.2% for arginine), highlighting their crucial role in fruit development. Further research is needed to investigate amino acid transport and distribution mechanisms between citrus leaves and fruits. [ABSTRACT FROM AUTHOR]

This study aimed to obtain angiotensin converting enzyme (ACE) inhibitory peptides from barley hordein, a protein rich in proline and glutamine, and to identify novel inhibitors. Hordein was hydrolyzed using four enzymes: pepsin, trypsin, papain, and orientase, an enzyme from Aspergillus oryzae known to cleave the C-terminal side of proline residues. The hydrolysate from orientase showed strong ACE inhibitory activity. LC-MS/MS analysis identified 35 peptides, including 23 derived from hordein and 9 known ACE inhibitors. After synthesizing 15 peptides, 7 showed significant ACE inhibition, all containing proline at the C-terminus. Notably, QQP, a new peptide, exhibited notable activity (IC50 40 μM). The results suggest that barley hordein is a valuable source of ACE inhibitory peptides, with QQP as a promising candidate. [ABSTRACT FROM AUTHOR]

Water deficit stress (WDS) is one of the most significant abiotic limiting factors in cultivated crops, including cotton (Gossypium barbadense L.). With global climate change and the destruction of ecological balance, the frequency and severity of drought events are increasing in many regions around the world. Therefore, the aim of the present work was to investigate the potential of using nano zinc particles (ZnO-NPs), plant growth-promoting rhizobacteria (Azospirillum sp.), and their combination to mitigate the negative impacts of WDS on cotton var. Giza 96. Extended irrigation intervals of 30 and 45 days led to considerable decreases in plant height, chlorophyll content, relative water content (RWC), yield, and cotton fiber quality compared to the optimal irrigation interval (every 15 days). When applied individually or in combination, ZnO-NPs and Azospirillum sp. can ameliorate the negative effects of WDS on cotton growth and productivity. Overall, the use of Azospirillum sp. and ZnO-NPs, either individually or in combination, has demonstrated their potential to enhance cotton growth and yield parameters (plant height, dry weight, leaf area, chlorophyll pigment, seed index, seed yield, and lint%) under prolonged irrigation intervals during 2021 and 2022 seasons. Antioxidant enzymes activity comprising catalase (CAT), peroxidase (POD), and polyphenol oxidase (PPO) and proline content were increased under drought stress. Cotton fiber quality parameters including length, strength, and micronaire were insignificantly affected under low irrigation rate. The combination of ZnO-NPs and Azospirillum sp. provided the most effective mitigation of WDS during both experimental seasons, outperforming the effects of individual applications. [ABSTRACT FROM AUTHOR]

Potato is cultivated all the year round in Pakistan. However, the major crop is the autumn crop which is planted in mid-October and contributes 80–85% of the total production. The abrupt climate change has affected the weather patterns all over the world, resulting in the reduction of the mean air temperature in autumn by almost 1.6 °C in Pakistan, which in turn, has adversely affected the crop performance and tuber yield. This trial, therefore, was conducted to optimize and evaluate the concentration of salicylic acid (SA) and potassium nitrate (KNO3) for inducing frost stress tolerance in an autumn-sown potato crop cv. Sutlej. The findings revealed that the foliar application of 0.5 mM SA significantly enhanced the growth, yield, fluorescent, and biochemical indices of potato plants outperforming 100 mM KNO₃ application in comparison with the control. This included increased plant height by 14% and 17.6%, leaf area index by 6.3% and 26.3%, shoot biomass by 15.4% and 46.2%, crop growth rate by 16.7% and 43.3%, average tuber weight by 8.2% and 23%, tuber diameter by 6.8% and 12.2%, tuber yield by 26.1% and 46.3%, leaf angle by 16.2% and 21.6%, quantum yield of photosystem II by 20.6% and 28.2%, photosynthetically active radiations by 20.5% and 32.4%, chlorophyll content by 6.3% and 14.6%, leaf thickness by 14% and 29%, linear electron flow by 20% and 32.7%, O–2 by 6% and 14.4%, H2O2 by 11.7% and 27.6%, enzyme activities of catalase by 20.7% and 28.5%, superoxide dismutase by 28.6% and 28.5%, peroxidase by 8.3% and 13.5%, ascorbate peroxidase by 17.2% and 37.8%, total protein by 21% and 37%, proline by 36.2% and 114%, and phenolic content by 33% and 63.3% with a reduction in non-photochemical quenching by 12.7% and 29.6%, non-regulatory energy dissipation by 169.5% and 268.5%, and leaf electrolyte leakage by 57.5% and 180%, compared to KNO3 and the control, respectively. Based on the above findings, it can be concluded and recommended that 0.5 mM foliar spray of SA can be utilized on potato crop cv. Sutlej in frost-sensitive regions. However, the application rate of KNO3 needs to be optimized in order to use its maximal frost stress tolerance potential. [ABSTRACT FROM AUTHOR]

Bell peppers are highly sensitive to salt stress, posing significant challenges for sustainable vegetables production especially bell pepper under suboptimal climatic conditions. Given the economic importance of bell peppers, enhancing their tolerance to salinity stress is a critical research focus over period. Silicon (Si) and potassium (K) and are crucial elements that have potential to combat salt stress significantly. This study aimed to investigate influential role of Si and K fertilization on root growth, physiological response, and fruit yield of bell pepper under salt stress. The factorial experiment included six fertilizer doses (F0: control- recommended fertilizer dose (RDF); F1: RDF + K30 (35 kg ha−1 K); F2: RDF + 60 kg ha−1 Si (soil); F3: RDF + K30 (35 kg ha−1 K) + 60 kg ha−1 Si (soil); F4: RDF + 100 ppm Si (foliar), and F5: RDF + K30 (35 kg ha−1 K) + 100 ppm Si (foliar) and five water salinity levels (control- 0.54, 3, 6, 9, and 12 dS m−1). Results revealed that root morphological traits particularly root biomass, root-shoot ratio, root length and root length density were significantly improved by RDF + K30 (35 kg ha−1 K) + 60 kg ha−1 Si (soil), followed by RDF + K30 (35 kg ha−1 K) + 100 ppm Si (foliar). At 12 dS m−1 salinity level, about 53% and 55% higher root and shoot biomass was reported at RDF + K30 (35 kg ha−1 K) + 60 kg ha−1 Si (soil) in compare to control. Leaf proline accumulation was increased with rising salinity levels which maximized by 51% at RDF + K30 (35 kg ha−1 K) + 60 kg ha−1 Si (soil) followed by 43% increase at RDF + K30 (35 kg ha−1 K) + Si (foliar) over control at 12 dS m−1 salinity level. Enhanced fruit yield was observed with various Si and K fertilization combinations, where RDF + K30 (35 kg ha−1 K) + 60 kg ha−1 Si (soil) shown a 62% and 40% higher yield in compare to control at 9 and 12 dS m−1 salinity levels, respectively. Collectively, incorporating Si and K with standard fertilizer demonstrated synergistic effects, to mitigate the adverse impacts of salt stress through up-regulating root-shoot morphological traits, physio-biochemical attributes and fruit yield of bell pepper. [ABSTRACT FROM AUTHOR]

Proline, a critical osmoregulatory compound, is integral to various plant stress responses. The P5CS gene, which encodes the rate-limiting enzyme in proline biosynthesis, known as ∆1-pyrroline-5-carboxylate synthetase, is fundamental to these stress response pathways. While the functions of P5CS genes in plants have been extensively documented, their specific roles in cotton remain inadequately characterized. In this study, we identified 40 P5CS genes across four cotton species with diverse sequence lengths and molecular weights. Phylogenetic analysis of 100 P5CS genes from nine species revealed three subgroups, with Gossypium hirsutum closely related to Gossypium barbadense. Collinearity analysis highlighted significant differences in collinear gene pairs, indicating evolutionary divergence among P5CS genes in tetraploid and diploid cotton. Exon–intron structures and conserved motifs correlated with phylogenetic relationships, suggesting functional differentiation. Stress-responsive elements in P5CS promoters suggest involvement in abiotic stress. Expression analysis under salt stress revealed differential expressions of GhP5CS genes, with GhP5CS1 emerging as a potential key regulator. Virus-induced gene silencing confirmed the pivotal role of GhP5CS1 in cotton's salt stress response, as evidenced by increased salt sensitivity in the silenced plants. This study enhances our understanding of the functional diversity and roles of P5CS genes in cotton under stress conditions. [ABSTRACT FROM AUTHOR]

The cover crop Pennisetum glaucum (L.) R.Br. (pearl millet) reduces the emergence of weed species in the field through a mechanism that is not fully known. The identification of the allelopathic activity of pearl millet can contribute to the development of no-tillage techniques to produce crops without or with low doses of herbicides. This issue was investigated by testing the effects of extracts from the aerial parts of pearl millet on the germination and growth of the weeds Bidens pilosa L., Euphorbia heterophylla L., and Ipomoea grandifolia (Dammer) O'Donell under laboratory conditions. The ethyl acetate fraction (EAF) at a concentration of 2000 µg mL−1 was inactive on Bidens pilosa; it inhibited root length (−72%) and seedling fresh weight (−41%) of E. heterophylla, and in I. grandifolia the length of primary root and aerial parts and the fresh and dry weight of seedlings were reduced by 63%, 32%, 25%, and 12%, respectively. In roots of I. grandifolia seedlings, at the initial development stage, EAF induced oxidative stress and increased electrolyte leakage. At the juvenile vegetative stage, a lower concentration of EAF (250 µg mL−1) induced a stimulus in seedling growth (+60% in root length and +23% in aerial parts length) that was associated with increased photosynthetic efficiency. However, at higher concentrations (1000 µg mL−1), it induced the opposite effects, inhibiting the growth of root (−41%) and aerial parts (−25%), with reduced superoxide dismutase activity and photosynthetic efficiency. The stilbenoid pallidol was identified as the main compound in EAF. The allelopathic activity of pearl millet may be attributed, at least in part, to the impairment of energy metabolism and the induction of oxidative stress in weed seedlings, with pallidol possibly involved in this action. Such findings demonstrated that the application of the EAF extract from pearl millet can be a natural and renewable alternative tool for weed control. [ABSTRACT FROM AUTHOR]

Background: Changes in the temperature induction response are potential tools for the empirical assessment of plant cell tolerance. This technique is used to identify thermotolerant lines in field crops. In the present investigation, ten-day-old seedlings of six wheat genotypes released by Dr. PDKV, Akola, Maharashtra, India were exposed to gradual increases in high temperature and duration (control 25 °C to 30 °C for 1 h, 34 °C for 1 h, 38 °C for 2 h and 42 °C for 3 h) to investigate their effects on some physiological and biochemical parameters to provide basic information for improving heat-tolerant cultivars. Results: Proline levels increased with increasing temperature up to 34 °C for 1 h but then decreased at higher temperatures (depending on genotype). Notably, proline levels decreased at 38 °C for 2 h in PDKV-Washim, AKAW-3722, and PDKV Sardar and at 42 °C for 3 h in all the genotypes. The relative leaf water content (RLWC) and chlorophyll 'b' content significantly decreased with increasing temperature. Hydrogen peroxide (H₂O₂) levels increased with temperature. The enzyme activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), and peroxidase also increased with temperature. However, these parameters, along with other biochemical indicators, generally decreased at 42 °C for 3 h. Conclusion: This study revealed positive relationships between increasing temperatures. Hydrogen peroxide levels and the activities of SOD, APX, and peroxidase enzymes across all the genotypes. The AKAW-4627 genotype presented better maintenance of physiological and biochemical parameters and lower H₂O₂ levels, indicating greater heat tolerance. Compared with PDKV-Washim and AKAW-3722, which are more susceptible to high temperatures, the WSM-109–04, AKAW-4627 and PDKV Sardar genotypes presented better adaptability to heat stress. These findings suggest that selecting wheat genotypes with higher proline accumulation and better maintenance of physiological and biochemical parameters under heat stress, such as AKAW-4627, can help in the development of heat-tolerant wheat cultivars. [ABSTRACT FROM AUTHOR]

Objective: The emergence of resistance in bacteria, and the existence of various types of infection and contamination in the hospital and community is the basis for research to find new antibacterial compounds. Materials: Ethyl Octahydrospiro [indene-2,3'-pyrrolizidine]-1,3-diones-pyrrolizidine]-2'carboxylate (5) was synthesized during one-pot reaction of ninhydrin, proline and ethyl acrylate in ethanol solvent. The antibacterial effect of the synthesized derivative on the mentioned bacteria was investigated by agar plate culture and broth micro dilution methods and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined for the synthesized derivative. Results: The analysis of the results showed that the MIC and MBC values of the newly synthesized compound against Staphylococcus aureus (S. aureus) bacteria were 1.56 and 3.12 µg/mlL., respectively. In addition, the MIC and MBC values of the synthetic compound against Escherichia coli (E. coli) were 0.39 µg/mlL and 0.78 µg/mlL, respectively. Conclusion: The antimicrobial test results revealed that the synthesized compound at an equivalent concentration exhibited a higher inhibitory impact on the Gram-negative E. coli bacteria than Gram-positive S. aureus. The compound causes the rapid bactericidal effect on Gram-negative bacteria by destroying or disrupting the function of the outer membrane. This combination could be effective in treating infections caused by Gram-negative bacteria. [ABSTRACT FROM AUTHOR]

Simple Summary: The razor clam Sinonovacula constricta, a commercially valuable marine bivalve species, is typically found in estuaries and coastal mudflat areas. However, limited research has been conducted on their adaptation mechanisms to high salinity stress. The present study provides the first comprehensive analysis of the members, gene structure, chromosome location, systematic evolution, and expression characteristics of the ALDH family in S. constricta following acute high salt stress. In this study, a total of 16 ScALDH genes were identified. Under acute salt stress, the expression of 14 members of the ScALDH family significantly changed, compared with when they were at 0 h, suggesting that the ScALDH gene family plays a crucial role in facilitating the regulation of osmotic pressure under salinity stress and adaptation. This study elucidated the gene characteristics, systematic evolution, and response to acute high salt stress of the ScALDH family, contributing valuable data to the understanding of the ALDH gene family in bivalves and providing a reference for further exploration into their role in osmotic stress regulation. The razor clam Sinonovacula constricta, a significant marine bivalve species, inhabits estuaries and encounters salinity stress. Despite its commercial importance, there is limited understanding of its adaptive mechanisms to high salinity. Aldehyde dehydrogenases (ALDHs), which belong to the NAD(P)+-dependent superfamily, play a crucial role in stress resilience by participating in catabolic and anabolic pathways, such as carnitine synthesis, glycolysis, and amino acid metabolism. This study presents the first comprehensive analysis of the ALDH family in S. constricta under acute high salt stress conditions and identifies 16 ScALDH genes across 10 subfamilies. These genes are located on eight chromosomes, with tandem duplications observed on chromosome 10; they encode mostly acidic and hydrophilic proteins. Among them, ScALDH18A1 contains a conserved P5CS domain that is implicated in proline synthesis and osmotic regulation. The expression of 14 ScALDH members were significantly altered under acute salt stress conditions, with ScALDH8 and ScALDH18A1 showing increased expression levels, suggesting their involvement in osmotic pressure regulation. This research provides insights into the characteristics, evolution, and response to salinity stress of the ScALDH gene family while shedding light on ALDH function in bivalves, as well as serving as a foundation for further studies on osmotic stress regulation. [ABSTRACT FROM AUTHOR]

Objective This study aimed to develop and validate a novel nomogram for diagnosing gastric cancer (GC). Methods In this prospective analysis, 146 patients of Wenzhou Central Hospital were recruited for a GC group and a benign lesion group and were divided into a training set and an internal validation set in a ratio of 7:3. Clinical and analytical characteristics were collected and analyzed by logistic regression analysis. The performance of the predictive model was evaluated using the receiver operating characteristic curve, calibration curve, and decision curve analysis. Results There were 5 variables, namely albumin, carcinoembryonic antigen, carbohydrate antigen 125, creatinine, and small proline-rich protein 2A, that were identified as the final parameters for the developed model. In the training and internal validation sets, the area under the curve of the model was 0.968 and 0.979, respectively, showing good diagnostic performance. Conclusion This study developed and validated a new nomogram based on 5 parameters. This model shows good diagnostic performance in distinguishing GC from benign lesion groups and has certain significance in clinical application. [ABSTRACT FROM AUTHOR]