Bartonella species, intracellular parasitic zoonotic pathogens, has drawn increasing attention for their diverse host range and associated human diseases. This study investigates Bartonella infection in small mammals in Yunnan Province, China, focusing on tissue tropism. 333 small mammals were sampled from 13 species, 3 orders, 4 families, and 4 genera in Heqing and Gongshan Counties. Conventional PCR and real-time quantitative PCR (qPCR) were utilized for detection and quantification, followed by bioinformatic analysis of obtained DNA sequences. Results show a 31.5% detection rate, varying across species. Notably, Apodemus chevrieri, Eothenomys eleusis, Niviventer fulvescens, Rattus tanezumi, Episoriculus leucops, Anourosorex squamipes, and Ochotona Thibetana exhibited infection rates of 44.4%, 27.7%, 100.0%, 6.3%, 60.0%, 23.5%, and 22.2%, respectively. Genetic analysis identified 30, 10, and 5 strains based on ssrA, rpoB, and gltA genes, with nucleotide identities ranging from 92.1% to 100.0%. Bartonella strains were assigned to B. grahamii, B. rochalimae, B. sendai, B. koshimizu, B. phoceensis, B. taylorii, and a new species identified in the Episoriculus leucops (GS136). Tissue distribution analysis revealed varied copy numbers across different tissues, with the highest load in spleen. These findings underscore Bartonella's diverse species and host range in Yunnan Province, highlighting its broad tissue tropism in small mammals.

The primary screening of hybridoma cells is a time-critical and laborious step during the development of monoclonal antibodies. Often critical errors occur in this phase, which supports the notion that the generation of monoclonal antibodies with hybridoma technology is difficult to control and hence a risky venture. We think that it is crucial to improve the screening process to eliminate most of the immanent deficits of the conventional approach. With this new microarray-based procedure, several advances could be achieved: Selectivity for excellent binders, high throughput, reproducible signals, avoidance of misleading avidity (multivalency) effects, and simultaneous performance of competition experiments. The latter can directly be used to select clones of desired cross-reactivity properties. In this paper, a model system with two excellent clones against carbamazepine, two weak clones and blank supernatant has been designed to examine the effectiveness of the new system. The excellent clones could be detected largely independent of the IgG concentration, which is unknown during the clone screening since the determination and subsequent adjustment of the antibody concentration is not possible in most cases. Furthermore, in this approach, the enrichment, isolation, and purification of IgG for characterization is not necessary. Raw cell culture supernatant can be used directly, even when fetal calf serum (FCS) or other complex media had been used. In addition, an improved method for the oriented antibody-immobilization on epoxy-silanized slides is presented. Based on the results of this model system, we conclude that this approach should be preferable to most other protocols leading to many of false positives, causing expensive and lengthy confirmation steps to weed out the poor clones.

Although several plant-derived drug groups (vinca alkaloids, taxanes, podophyllotoxin derivatives and camptothecins) continue to be widely used in cancer therapy, the anticancer potential of the Plant Kingdom remains largely unexplored. In this work, we have carried out a random screening for selective anticancer activity of 57 extracts from 45 plants collected in Grazalema Natural Park, an area in the South of Spain of high plant diversity and endemism. Using lung cancer cells (A549) and lung non-malignant cells (MRC-5), we found that several extracts were more cytotoxic and selective against the cancer cell line than the standard anticancer agent cisplatin. Five active extracts were further tested in cancer and normal cell lines from other tissues, including three skin cell lines with increasing degree of malignancy. An extract from the leaves of Daphne laureola L. (Thymelaeaceae) showed a striking potency and selectivity on lung cancer cells and leukemia cells; the IC₅₀ values against these cancer cells were approximately 10000-fold lower than against the normal cells. Daphnane-type diterpene orthoesters may be responsible for this highly selective anticancer activity.

Lower cutoff levels in screening programs have led to an increase in the proportion of detected cases with transient hypothyroidism, leading to increase of the overall incidence of primary congenital hypothyroidism (CH) in several countries. We have performed retrospective evaluation on the data from 251,008 (96.72%) neonates screened for thyroid-stimulating hormone (TSH) level in dried blood spot specimens taken 48 hours after birth, between 2002 and 2015, using DELFIA method. A TSH value of 15 mIU/L was used as the cutoff point until 2010 and 10 mIU/L thereafter. Primary CH was detected in 127 newborns (1/1976) of which 81.1% had permanent and 18.9% had transient CH. The incidence of primary CH was increased from 1/2489 until to 2010 to 1/1585 thereafter (p=0.131). However, the incidence of permanent CH was slightly increased (p=0.922), while the transient CH incidence had 8-fold increasing after lowering the TSH cutoff level (p<0.001). In cases with permanent CH, we observed lower frequency for thyroid dysgenesis (82.7 vs. 66.7%) and higher frequency for normal in-situ thyroid gland (17.3 vs. 33.3%), for the period with reduced TSH cutoff value. Our findings support the impact of lower TSH cutoff on the increasing incidence of congenital hypothyroidism.

Advanced glycation end products (AGEs) play a significant role in the aging processes, further regarding as a hallmark of aging. Despite the importance, a lack of monitoring tools has hampered the study of relationship between AGEs and aging. Here, we firstly report a novel AGEs-selective probe, AGO. AGO presented its ability to detect AGEs more sensitively than a conventional approach of measuring autofluorescence from AGEs. In addition, we confirmed that AGO can detect AGEs depending on kinetics, reflecting by a preference to ribose-derived AGEs. Finally, AGO revealed its competence to visualize glycation products in glycation mimicking model, made by collagen framework. We believe that this study will enrich molecular toolboxes to understand physiological processes of AGEs during aging processes.

The dopamine D3 receptor is an important CNS target for the treatment of a variety of neurological diseases. Selective dopamine D3 receptor antagonists modulate the improvement of psychostimulant addiction and relapse. In this study, five and six featured pharmacophore models of D3R antagonists were generated and evaluated with the post-hoc score combining two survival scores of active and inactive. Among Top 10 models, APRRR215 and AHPRRR104 were chosen based on the coefficient of determination (APRRR215: R2training = 0.80; AHPRRR104: R2training = 0.82) and predictability (APRRR215: Q2test = 0.73, R2predictive = 0.82; AHPRRR104: Q2test = 0.86, R2predictive = 0.74) of their 3D-quantitative structure–activity relationship models. Pharmacophore-based virtual screening of a large compound library from eMolecules (> 3 million compounds) using two optimal models expedited the search process 100-fold speed increase compared to the docking-based screening (HTVS scoring function in Glide) and identified a series of hit compounds having promising novel scaffolds. After the screening, docking scores, as an adjuvant predictor, were added to two fitness scores (from the pharmacophore models) and predicted Ki (from PLSs of the QSAR models) to improve accuracy. Final selection of the most promising hit compounds were also evaluated for CNS-like properties as well as expected D3R antagonism.

Glioblastoma (GBM) is the most common malignant brain tumor in adults. Despite advancements in treatment, the prognosis for patients with GBM remains poor due to its aggressive nature and resistance to therapy. CRISPR-based genetic screening has emerged as a powerful tool for identifying genes crucial for tumor progression and treatment resistance, offering promising targets for tumor therapy. In this review, we provide an overview of the recent advancements in CRISPR-based genetic screening approaches and their applications in GBM. We highlight how these approaches have been used to uncover genetic determinants of GBM progression and susceptibility to various therapies. Furthermore, we discuss ongoing challenges and future directions of CRISPR-based screening methods in advancing GBM research.

Fluorescent bioprobes are invaluable tools for visualizing live cells and deciphering complex biological processes by targeting intracellular biomarkers without disrupting cellular functions. In addition to protein-binding concepts, fluorescent probes utilize various mechanisms, including membrane, metabolism, and gating-oriented strategies. This study introduces a novel fluorescent mechanism distinct from existing ways. Here, we developed a B-cell selective probe, CDrB, with unique transport mechanisms. Through SLC-CRISPRa screening, we identified two transporters, SLCO1B3 and SLC25A41, by sorting out populations exhibiting higher and lower fluorescence intensities, respectively, demonstrating contrasting activities. We confirmed that SLCO1B3, with comparable expression levels in T and B cells, facilitates the transport of CDrB into cells, while SLC25A41, overexpressed in T lymphocytes, actively exports CDrB. The observation suggests that SLC25A41 plays a crucial role in discriminating between T and B lymphocytes. Furthermore, it reveals the potential for reversible localization of SLC25A41 to demonstrate its distinct activity. This study is the first report to unveil a novel strategy of SLC by exporting the probe. We anticipate that this research will open up new avenues for developing fluorescent probes.

In our continuous search for selective anticancer treatments, we have screened 65 extracts from 45 plants collected in several areas of Western Andalusia (Spain) for cytotoxic activity against lung cancer cells and lung normal cells. Active extracts were also tested against 11 cell lines from other tissues. An extract from the leaves of Tetraclinis articulata (Vahl) Mast. (Cupressaceae) showed a marked cytotoxicity (IC₅₀ = 0.37 ± 0.03 µg/mL) and selectivity (selectivity index = 378.3) against the lung cancer cells; cisplatin, 5-fluorouracil and an extract from the leaves of Taxus baccata L. (Taxaceae) were less cytotoxic and selective.

Thromboembolic conditions, such as stroke and myocardial infarction [MI], are the primary causes of mortality globally. High efficiency was demonstrated by fibrinolytic enzymes isolated from microbial sources in dissolving various blood clots. The study aimed to investigate and produce bacterial fibrinolytic enzymes from various Egyptian soil conditions using recombinant DNA technology. Fifty soil samples were examined to determine the production of fibrinolytic enzymes. The plasmin plate technique assessed the thrombolytic activities of the strong fibrinolytic enzyme-producing bacterial isolates. In addition to determining the molecular mass using a mass spectrometer and the western blot method, the activity and thermostability of the enzymes were characterized. An affinity chromatography approach was used to purify the fibrinolytic enzymes. However, bacterial recombinant DNA technology produced the pure bacterial fibrinolytic enzyme. Several dosage formulations for the formulation of fibrinolytic enzymes were tested. By using affinity chromatography and the SDS-PAGE test, the isolated bacterial fibrinolytic enzyme in this investigation was almost 83% pure. Bacillus cereus ATCC 4342 was identified as the predominant bacterial isolate secreting fibrinolytic enzymes. It was discovered that the fibrinolytic enzyme activity of fifty soil samples ranged from 0.167 U/ml to 1.853 U/ml. The extracellular enzyme extracted from Bacillus cereus culture supernatant demonstrated a relatively stable fibrinolytic activity over 18 hours at a pH range of 7.4–10, as well as stability with maximum productivity at 43℃ for over 60 minutes. In this investigation, the enzyme was referred to as Fibrin-proteinase[ FP]. The fibrin clots were directly thrombolyzed by the FP. The calculated values for the specific activity and molecular mass of the FP were approximately 40.71 units/mg of protein and approximately 30 KDa, respectively. It was observed that the presence of Fe+3 marginally boosted protease activity, but the presence of EDTA decreased it. On the other hand, adding monovalent cations like K+1 and Na+1 significantly increased the fibrinolytic activity of FP. The enzyme exhibited activity throughout the temperature range of 20 to 65℃, peaking at 55℃. The ideal range for the generation of protease was 35–43℃ and 8.0–10. The thermostable fibrinolytic enzyme FP, which was isolated from Bacillus cereus ATCC 4342 in various soil environments in Egypt during the current study, was a promising fibrinolytic enzyme because it demonstrated a more extensive and effective fibrinolytic activity and fewer side effects than the fibrinolytic enzymes that are currently available worldwide. It is advised that further research be done on optimizing the right formulation of bacterial fibrinolytic enzymes in the future to help dissolve different types of blood clots and, as a result, lower the high death rate that exists worldwide.

In the case of a Cu-Mo-W polymetallic ore, the wastewater from the scheelite cleaning flowsheet contains large amounts of residual flocculants and metal ions, and the separation of chalcopyrite and molybdenite require a large number of environmentally harmful depressants. Therefore, it is necessary to find new methods to reduce the environmental and cost pressures of wastewater treatment and the use of depressants. In this work, the flotation wastewater from scheelite cleaning flowsheet for the separation of chalcopyrite and molybdenite by selective surface passivation was investigated for the first time. Flotations of single minerals and artificially mixed minerals with or without immersion pretreatment in the presence and absence of aeration were performed. The results showed that pulp pH had no effect on the flotation of either mineral, and a molybdenite recovery of 93.22% with chalcopyrite recovery of 10.77% was achieved under the conditions of 10 days of immersion pretreatment with aeration, 350 mg/L of kerosene, and 100 mg/L of MIBC. By combining the electrochemical cyclic voltammetry analysis and characterization by XRD and SEM, the selective surface passivation mechanism of chalcopyrite was discussed, which could be due to the coverage of the insoluble oxidation products, especially jarosite. This work has simultaneously achieved the depressant-free flotation separation of molybdenite and chalcopyrite and the reuse of scheelite flotation wastewater, which is of great significance for environmental protection and cost saving.

Wavelength selective switches (WSSs) are essential elements for wavelength division multiplexing (WDM) optical networks, as they offer cost-effective, high port-count and flexible spectral channel switching. This work proposes a new hybrid WSS architecture that leverages the beam shaping and steering features of uniform silicon nitride (SiN) based end-fire optical phased arrays (OPAs). By introducing beamforming to a WSS system, the spectral channels on the liquid crystal on silicon (LCoS) panel can be tailored and arranged properly, depending on the optical configuration, using the beam control capabilities of OPAs. Combining 3D-FDTD and ray tracing simulations, the study shows that by reducing the input beam dimensions with proper sizing of the OPAs, the WSS design with the null-steering OPAs layout and 4×No switch size features increased spectral resolution. This extensive beamforming study on the steering-enabled layout reveals the acquirement of an even higher input channel number, achieving up to the 8×No WSS scheme with flexible channel routing on the LCoS panel. Such implementation of beamsteerers can unlock an extra degree of freedom for the switching capabilities of hybrid WSS devices. The results show great promise for the introduction of OPAs in WSS systems and provide valuable insight for the design of future wireless communication links and WDM systems.

BACKGROUND: Thromboembolic disorders including Myocardial infarction[ MI] and stroke represent the leading causes of death worldwide. Fibrinolytic enzymes extracted from microbial sources showed high efficacy in the dissolution of different blood clots. AIM OF THE STUDY: Screening and the bacterial recombinant DNA manufacture of bacterial fibrinolytic enzymes from different soil environments in Egypt. METHODOLOGY: A total of 50 soil samples were screened for their fibrinolytic enzyme production. The potent fibrinolytic enzyme-producing bacterial isolates were evaluated for their thrombolytic activities using the plasma plate method. The characterization of the enzyme activity and thermostability were carried out; also, the determination of molecular mass using a mass spectrometer and western blot technique was performed. The purification of the fibrinolytic enzymes was done through the affinity chromatography technique. On the other hand, the production of the purified bacterial fibrinolytic enzyme was achieved via bacterial recombinant DNA technology. Formulation of fibrinolytic enzymes in different dosage forms was tried. RESULTS: In the present study, the purified bacterial fibrinolytic enzyme was approximately 83% pure through affinity chromatography and SDS-PAGE assay. The predominating bacterial isolate secreting fibrinolytic enzymes was found to be Bacillus cereus. The fibrinolytic enzyme activities of 50 soil samples were found to be in the range of 0.167-1.853 U/ ml. The fibrinolytic activity of the extracellular enzyme refined from the culture supernatant of Bacillus cereus was relatively stable over the PH range from 7.4-10 for 18 hours and also it showed stability with the highest productivity at a temperature of 43 0C for nearly 60 minutes. The enzyme was called fibrin-proteinase[ FP] in the present study. The FP degraded the fibrin clots via direct thrombolysis. The specific activity and the molecular mass of the FP were estimated to be nearly 40.71 Units/ mg protein and nearly 30 KDa respectively. Protease activity was noticed to be slightly increased in the presence of Fe+3; While it was inhibited in the presence of EDTA. On the other hand, the FP fibrinolytic activity was enhanced greatly after the addition of monovalent cations such as K+1 and Na +1. The enzyme was also active over the temperature range of 20- 65 0C with the highest activity at 55 0C. The optimum temperature and PH of protease production was at 35-43 0C and PH 8.0-10. Conclusion: During the present study, the thermostable fibrinolytic enzyme FP purified from Bacillus cereus in different soil environments in Egypt was a promising fibrinolytic enzyme because it showed a broader efficacious fibrinolytic activity as well as less adverse effects than the current fibrinolytic enzymes globally. It is recommended in the future advanced exploration of the optimization of suitable formulation of bacterial fibrinolytic enzymes to aid in the dissolution of various blood clots and as a consequence overcoming the high rate of mortality globally.

Spinocerebellar ataxia type 3 is a neurodegenerative disease caused by an abnormal expansion of CAG repeats in the disease gene ATXN3, leading to prolonged polyglutamine (polyQ) tracts in the respective protein ataxin-3. The polyQ-expanded protein forms polyQ-containing aggregates in several brain regions which leads to neuronal cell loss. Autophagy is thought to play a significant role in clearing these polyQ-containing protein aggregates. Therefore, the autophagy mechanism was investigated in SCA3 with focus on the autophagic protein p62/sequestosome-1. Human and mouse RNA sequencing data were analyzed to determine RNA expression level of autophagic genes. Additionally, autophagy was studied in the SCA3 304Q knock-in mouse model and through several cell culture experiments using HEK-293T cells transfected with ATXN3 of differ-ent polyQ lengths. For cell culture experiments, autophagy was induced with rapamycin treat-ment, proteasomal degradation was blocked with MG132 and degradation of autophagic pro-teins was investigated using cycloheximide treatment. Here, we report an increased autophagy impairment with SCA3 disease progression seen in HEK-293T cells transfected with ATXN3 plasmid with expanded polyQ tracts, higher aged 304Q-knock-in mice, or human post-mortem brain material. Furthermore, co-localized aggregation of the autophagic protein p62 and the dis-ease protein ATXN3 was observed in the course of SCA3 disease. Therefore, we suggest a signifi-cant role for p62 in aggregate formation seen in the neurodegenerative disease SCA3.

(1) Background: The prediction of cervical lesions evolution is a challenge for clinicians. The prospective study aimed to determine and compare the predictive accuracy of cytology, HPV genotyping, and p16/Ki67 dual staining alone or in combination with personal risk factors for the prediction of progression, regression or persistence of cervical lesions in human papillomavirus (HPV)-infected patients; (2) Methods: This prospective study included HPV-positive patients with or without cervical lesions that underwent follow-up. Descriptive statistics and sensitivity analysis for individual or combined index tests were used for data analysis; (3) Results: The highest predictive performance for the progression of cervical lesions was achieved by a model that comprised a Pap smear suggestive of high-grade squamous intraepithelial lesion (HSIL), the presence of 16/18 HPV strains, a positive p16/Ki67 dual staining result along with the presence of at least 3 clinical risk factors, which had a sensitivity (Se) of 74.42%, a specificity of 97.92%, an area under the receiver operating curve (AUC) of 0.961, and an accuracy of 90.65%. The prediction of cervical lesions regression or persistence was modest; (4) Conclusions: Multiple testing or new biomarkers should be used to improve HPV-positive patient surveillance, especially for cervical lesion regression or persistence prediction.

Landiolol is an ultra-short-acting, selective ß1- adrenergic receptor blocker that was originally approved by Japan for the treatment of intraoperative tachyarrhythmias. It has gained attention for its use in the management of tachyarrhythmias and perioperative tachycardia, especially atrial fibrillation for both cardiac and non-cardiac surgeries. It can be the ideal agent for heart rate control due to its high β1‐selectivity, the potent negative chronotropic effect, a limited negative inotropic potential, and an ultrashort elimination half‐life (around 4 min); moreover, it may have a potential therapeutic effect for sepsis and pediatric patients. Landiolol seems to be superior to other short‐acting and selective beta‐blockers such as esmolol. This review aims to provide a comprehensive overview of landiolol, a new ultra-short-acting ß1 selective antagonist, including its pharmacology, clinical applications, efficacy, safety profile, and future directions in research and clinical data.

A time-sequential working, spatially multiplexed autostereoscopic 3D display design consisting of a fast switchable RGB-color filter array is presented. The wavelength-selective filter barrier emits the light from a display over a larger active area than common autostereoscopic barrier displays. An optical modelling of wavelength-selective barriers has been used for instance to calculate the light ray distribution properties of that arrangement. To find well working display designs, automated searches by simulation and computational evaluation has been proceeded. Wavelength-selective filter barrier arrangements exhibit characteristics different from common barrier displays with similar barrier pitch and ascent. In particular, these constructions show strong angular luminance dependency under barrier inclination specified by correspondent slant angle. In time-sequential implementation it is important to avoid that quick eye or eyelid movement lead to visible color artifacts. In the millisecond regime tunable liquid crystal Fabry-Pérot color filters for the colors red, green and blue are presented. They consist of a sub-micrometer thick nematic layer sandwiched between dielectric mirrors and ITO-electrodes. These cells shall switch narrow-banding light of red, green or blue. An array for a glasses-free 3D display has to be equipped with several thousand switchable filter elements having different color apertures. The newly introduced design is usable as a multi user display as well as a single user system with user adaptive control.

To enhance the applicability of dual-phase high-entropy alloys (HEAs) like Fe32Cr33Ni29Al3Ti3, fabricated via selective laser melting (SLM), a focus on improving their mechanical properties is essential. As part of this effort, heat treatment was explored. This study compares the microstructure and mechanical properties of the as-printed sample with those cooled in water after undergoing heat treatment at temperatures ranging from 1000 to 1200 ℃ for 1 hour. Both pre- and post-treatment samples reveal a dual-phase microstructure comprising FCC and BCC phases. Although heat treatment led to a reduction in tensile and yield strength, it significantly increased ductility compared to the as-printed sample. This strength-ductility trade-off is related to changes in grain sizes with ultrafine grains enhancing strength and micron grains optimizing ductility, also the influence of the content of FCC/BCC phases and dislocation density. In particular, the sample heat-treated at 1000 °C for 1 hour and then water-cooled exhibited a better combination of strength and ductility, a yield strength of 790 MPa, and an elongation of 13%. This research offers innovative perspectives on crafting dual-phase HEA of Fe32Cr33Ni29Al3Ti3, allowing for tailorable microstructure and mechanical properties through a synergistic approach involving SLM and heat treatment.

From 2008 to 2024, the Newborn Screening Translational Research Network (NBSTRN), part of the National Institute of Child Health and Human Development (NICHD) Hunter Kelly Newborn Screening Program, served as a robust infrastructure to facilitate groundbreaking research in newborn screening (NBS), rare disease, and genomics. Over fifteen years, NBSTRN developed into a significant international network, supporting innovative research on novel technologies to screen, diagnose, treat, manage, and understand the natural history of more than 280 rare diseases. A key component of these efforts has been the development of resources and expertise for the newborn screening community in ethical, legal, and social issues (ELSI). This paper presents findings from a survey conducted by the NBSTRN team with input from one of theNBSTRN's expert workgroups, the Bioethics and Legal Workgroup. With responses from 88 members of the NBS community including researchers and state NBS programs, the survey found that individuals rely on internal and collegial ELSI resources and highlighted a substantial demand for structured, accessible training and resources. The survey’s insights emphasize the importance of privacy and informed consent in NBS research, and suggested a need for improved collaborative tools and educational programs focused on ELSI for the NBS community. The survey results may inform future efforts in ELSI and NBS research including the development of expanded ELSI tools that leverage digital platforms and consultative services.

Sarcopenia is associated with clinical complications, which increase mortality. Effective sarcopenia risk screening in the elderly should be grounded in a comprehensive assessment, encompassing both nutritional status and medication use. Current screening tools, while emphasizing muscular per-formance, exhibit limited sensitivity in identifying elderly individuals at risk of sarcopenia. This cross-sectional study aimed to develop a sarcopenia risk screening tool, named Sarc-Global, with enhanced sensitivity, incorporating factors pertinent to the overall health of the elderly. Utilizing the criteria established by EWGSOP2 for diagnosing sarcopenia, we evaluated 395 communi-ty-dwelling elderly individuals. This evaluation served as a reference for assessing the efficacy of two validated questionnaires, Sarc-F and Sarc-CalF, and our newly developed Sarc-Global. Con-structed through multiple logistic regression, Sarc-Global integrates variables such as sex, age, medication use, body mass index, arm circumference, and handgrip strength – all significantly associated with sarcopenia (p

Residual stress (RS) is the most challenging problem in metal additive manufacturing (AM) since the build-up of high tensile RS may influence the fatigue life, corrosion resistance, crack initiation, and failure of the additively manufactured components. While tensile RS is inherent in all the AM processes, fast and accurate prediction of stress state within the part is extremely valuable and would result in optimization of the process parameters in achieving a desired RS and control of the build process. This paper proposes a physics-based analytical model to rapidly and accurately predict the RS within the additively manufactured part. In this model, a transient moving point heat source (HS) is utilized to determine the temperature field. Due to the high temperature gradient within the proximity of the melt pool area, material experience high thermal stress. Thermal stress is calculated by combining three sources of stresses known as stresses due to the body forces, normal tension, and hydrostatic stress in a homogeneous semi-infinite medium. The thermal stress determines the RS state within the part. Consequently, by taking the thermal stress history as an input, both the in-plane and out of plane RS distributions are found from incremental plasticity and kinematic hardening behavior of the metal by considering volume conservation in plastic deformation in coupling with the equilibrium and compatibility conditions. In this modeling, material properties are temperature-sensitive since the steep temperature gradient varies the properties significantly. Moreover, the energy needed for the solid-state phase transition is reflected by modifying the specific heat employing the latent heat of fusion. Furthermore, the multi-layer and multi-scan aspects of metal AM are considered by including the temperature history from previous layers and scans. Results from the analytical RS model presented excellent agreement with XRD measurements employed to determine the RS in the Ti-6Al-4V specimens.

Structures inevitably suffer damages after an earthquake, with their severity ranging from minimal damages to non-structural elements to partial or even total collapse, possibly with loss of human lives. Thus, it is essential for engineers to understand the crucial factors that drive a structure towards suffering higher degrees of damage, so that preventative measures can be taken. In the present study, we focus on three well-known damage thresholds, namely Collapse Limit State, Ultimate Limit State and Serviceability Limit State and analyze which of the features obtained via Rapid Visual Screening, determine whether or not a given structure will cross that threshold. To this end, we use Machine Learning to perform binary classification for each damage threshold, as well as Explainability via SHAP values (acronym for SHapley Additive exPlanations) to quantify the effect of each parameter. The quantitative results obtained demonstrate the potential applicability of ML methods to re-calibrate the computation of structural vulnerability indices using data from recent earthquakes.

Gestational diabetes mellitus (GDM) pathophysiology comprises clinical and genetic factors. In fact, GDM has been associated with several single nucleotide polymorphisms (SNPs). This study aimed to build a prediction model of GDM combining clinical and genetic risk factors. A total of 1588 pregnant women from the San Carlos Cohort participated in the present study, 1069 (67.3%) Caucasian (CAU) and 519 (32.7%) Latin American (LAT), 255 (16.1%) with GDM. The incidence of GDM was similar in both groups (16.1% CAU and 16.0% LAT). Genotyping was performed by IPLEX Mass ARRAY PCR selecting 110 SNPs based on literature references. The SNPs showing the strongest likelihood of GDM development were the rs10830963, rs7651090 and rs1371614 in CAU and rs1387153 and the rs9368222 in LAT. Clinical variables including age, pre-pregnancy body mass index and fasting plasma glucose (FPG) at 12 gestational weeks predicted the risk of GDM (AUC 0.648, 95%CI 0.601-0.695 in CAU; AUC 0.688, 95%CI 0.628-9.748 in LAT) and adding the SNPs modestly improved prediction (AUC 0.722, 95%CI 0.680-0.764 in CAU; AUC 0.769, 95%CI 0.711-0.826 in LAT). In conclusion, adding genetic variants enhanced the prediction model of GDM risk in CAU and LAT pregnant women. An RCT is underway to demonstrate its usefulness

Congenital heart disease (CHD) is a prevalent congenital disorder diagnosed with high frequency, affecting approximately 0.8% to 1.2% of all live births. Research has demonstrated that the use of pulse oximetry and clinical examination as a screening tool for CHD diagnosis has proven extremely valuable. We conducted a retrospective longitudinal study over a 3-year period that involved screening 1188 newborns admitted to the NICU during the first 72 hours of life within this timeframe. 201 newborns were diagnosed with CHD. Almost all (n=198) had a positive screening test during the 72-hour period, while 3 had a negative screening test, but were later diagnosed using echocardiography. The prevalence rate was 16.67%. A confusion matrix was constructed with 198 true positives (TP), 3 false negatives (FN), no false positives (FP), and 987 true negatives (TN). The sensitivity of the screening test was 98.51%, while the specificity 100%, with no false positives. In our study, a total of 9 deaths occurred. Using the Kaplan-Meier method, the survival probability appeared to be slightly above 0.9 (95.5%), indicating that almost all patients survived past 72 hours after being diagnosed with CHD. Pulse oximetry is an effective, low cost and easy-to-use method and a useful tool to assess and lead to the diagnosis of CHD.

Bat feces were reported in ancient Chinese medicine books to have the effect of reducing heat and improving eyesight, but the mechanism of vision improvement still needs further research. To this end, we used 2,2-diphenyl-1-picrylhydrazyl (DPPH) and liquid chromatography/tandem mass spectrometry (LC/MS/MS) to analyze the antioxidant capacity of and the types of vitamins in bat feces. We hoped to screen the pharmacological components of bat feces, and to explain the role that these components may play in the treatment of visual deterioration. Our results found that bat feces had a good antioxidant capacity and mainly contain vitamins B1 (thiamine), B2 (riboflavin), B3 (nicotinamide), B3 (nicotinic acid), and B5 (pantothenic acid). Although these vitamins may help maintain the health of the optic nerve and cornea, the vitamin content of bat feces is low, but the heavy metal content is high, as shown using inductively coupled plasma mass spectrometry (ICP-MS) analysis. Therefore, we suggest that the use of bat feces as traditional Chinese medicine to improve vision should be strictly restricted.

Malnutrition is a serious problem with negative impact on the quality of life and the evolution of our patients, contributing to an increase in morbidity, hospital stay, mortality and health spending. Early identification is fundamental to implement the necessary therapeutic actions involving adequate nutritional support to prevent or reverse malnutrition. This review presents two complementary methods of fighting malnutrition: nutritional screening and nutritional assessment. Nutritional risk screening is conducted using simple, quick-to-perform tools and is the first line of action in detecting at-risk patients. It should be implemented systematically and periodically on admission to hospital or residential care, as well as on an outpatient basis for patients with chronic conditions. Once patients with a nutritional risk have been detected they should undergo a more detailed nutritional assessment to identify and quantify the type and degree of malnutrition. This should include health history and clinical examination, dietary history, anthropometric measurements, evaluation of the degree of aggression determined by the disease, functional assessment and, whenever possible, some method of measuring body composition.

Rapid advances in the screening, diagnosis, and treatment of genetic disorders has increased the number of conditions that could be detected through universal newborn screening (NBS). However, addition of conditions to the Recommended Uniform Screening Panel (RUSP) and implementation of nationwide screening has been a slow process taking several years to accomplish for individual conditions. Here we describe web-based tools and resources developed and implemented by the newborn screening translational research network (NBSTRN) to advance newborn screening research and support NBS stakeholders. NBSTRN’s tools include the Longitudinal Pediatric Data Resource (LPDR), the NBS Condition Resource (NBS-CR), the NBS Virtual Repository (NBS-VR), and the Ethical, Legal, and Social Issues (ELSI) Advantage. Research programs including the Inborn Errors of Metabolism Information System (IBEM-IS), BabySeq, EarlyCheck, and Family Narratives Use Cases have utilized NBSTRN’s tools, and in turn contributed research data to further expand and refine these this resource. Additionally, we discuss ongoing tool development to facilitate expansion of genetic disease screening in increasingly diverse populations. In conclusion, NBSTRN’s tools and resources provide a trusted platform to enable NBS stakeholders to advance NBS research and improve clinical care for patients and their families.

The blood counts of α thalassemia carriers (α-thal) are similar to those of β thalassemia carriers, except for Hgb A2 that is not elevated. The objective of this study was to determine whether mathematical formulas are effective for detecting suspected α-thal. The data were obtained from the database of the prevention program for detecting couples at risk for having a child with hemoglobinopathy. RBC indices were analyzed using mathematical formulas and the sensitivity and negative predictive value (NPV) calculated. Among 1334 blood counts suspected α-thal analyzed, only the Shine&Lal and the Support Vector Machine formulas revealed high sensitivity and NPV. Sensitivity was 85.54 and 99.33% and NPV 98.93 and 99.93%, respectively. Molecular defects were found in 291, 81 had normal α genes. Molecular analysis was not performed in 962. Based on these results, mathematical formulas incorporating one of these reliable formulas for detecting suspected α or β thalassemia carriers in the program of the automatic analyzers can flag these results and increase the awareness of the primary physicians about the carrier risk and send an alert with a recommendation for further testing.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents unexplained and sudden deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for prolonged QTc or Long QT Syndrome (LQTS) should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiogram (ECG) could identify congenital heart defects (CHD) early, especially those not detected at birth. Infants with prolonged QT intervals typically undergo genetic analysis for Long QT Syndrome; (2) Methods: The study involved infants aged 20-40 days, born clinically healthy, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHD identified immediately after birth, as well as those who underwent ECG or echocardiogram for other clinical or historical indications, were excluded from the study. The data were analyzed using SPSS version 22.0; (3) Results: Of the 42,200 infants involved, 2,245 were enrolled, with 39.9% being males. Subsequently, 164 children (37.8% males) with prolonged QT intervals underwent further diagnostic investigations. Genetic mutations were identified in 11 out of 18 tested children. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Medications used included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%; (4) Conclusions: The screening has proven effective in early diagnosing Long QT Syndrome and other cardiac rhythm anomalies, with additional benefits in detecting mutations and/or QTc prolongations in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.

Beta adrenoblockers is a large class of drugs mainly used to manage abnormal heart rhythms. Over the last couples of decades, the anticancer effects of these compounds has been extensively studied. There is much evidence about their activity in non-small cell lung, pancreatic, breast, colorectal, prostate and ovarian cancer. However, the mechanism of beta blockers anticancer activity is still not known, and more detailed studies are needed. The aim of our study was to evaluate the anticancer activity of beta adrenoblockers in non-small cell lung cancer cell lines A549 and H1299. In order to find the relationship with their selectivity to beta adrenoreceptors, in our study we used selective (atenolol, betaxolol, esmolol, metoprolol) and non-selective (pindolol, propranolol and timolol) beta blockers. The effect on cell viability was evaluated by MTT assay and the activity on cell ability to form colonies was tested by clonogenic assay. The type of cell death was evaluated by cell double staining with Hoechst 33342 and Propidium iodide. The most active adrenoblockers against both tested cancer cell lines were propranolol and betaxolol. They completely inhibited lung cancer cell colony formation at 90% of EC50 (half maximal effective concentration) value. Most tested compounds induced cell death through apoptosis and necrosis. In A549 cell lines apoptosis was mainly induced while in H1299 cell line compounds induced both apoptosis and necrosis. There was no correlation established between beta adrenoblocker anticancer activity and their selectivity to beta adrenoreceptors.

Outbreaks of the crown-of-thorns seastar (CoTS) represent a major cause of coral loss on the Great Barrier Reef. Outbreaks might be explained by enhanced larval survival supported by higher phytoplankton availability after flood events, yet little is known about CoTS larvae feeding behaviour, in particular their potential for selective feeding. Here, single- and mixed-species feeding experiments were conducted on CoTS bipinnaria larvae using five algae (Phaeodactylum tricornutum, Pavlova lutheri, Tisochrysis lutea , Dunaliella sp. and Chaetoceros sp.) and two algal concentrations (1000 and 2500 algae mL^-1). Cell counts using flow-cytometry at the beginning and end of each incubation experiment allowed us to calculate the filtration and ingestion rates of each species by CoTS larvae. In line with previous studies, CoTS larvae ingested more algae when initial algal concentration was higher. We found evidence for the selective ingestion of some species (Chaetoceros sp., Dunaliella sp.) over others (P. lutheri, P. tricornutum). The preferred algal species had the highest energy content, suggesting that CoTS selectively ingested the most energetic algae. Ultimately, combining these results with spatio-temporal patterns in phytoplankton communities will help elucidate the role of larval feeding behaviour in determining the frequency and magnitude of CoTS outbreaks.

A study has been carried out on Ta and Nb recovery by liquid-liquid extraction process using 4-methylacetophenone (4-MAcPh) as organic phase. The 4-MAcPh was compared to methylisobutylketone (MIBK) with respect to extraction efficiencies (kD values) at different concentrations of H2SO4 in the aqueous phase. The results showed a similar extraction of Nb for both solvents. However, for Ta extraction efficiency is increased by a factor of 1.3 for 4-MAcPh. In addition, the MIBK solubilized completely after 6 mol L-1 of H2SO4 against only a loss of 0.14 to 4% for 4-MAcPh between 6 and 9 mol L-1 of H2SO4. The potential of 4-MAcPh has also been studied to selectively recover Ta from a model capacitor waste solution. The results showed a selectivity for Ta in the presence of impurities such as Fe, Ni, Mn. The 4-MAcPh also presents the advantage of having physicochemical properties adapted to its use in liquid-liquid extraction technologies such as mixer-settlers.

In order to understand the evolution of multicellularity, we must understand how and why selection favors the first steps in this process: the evolution of simple multicellular groups. Multicellularity has evolved many times in independent lineages with fundamentally different ecologies, yet no work has yet systematically examined these diverse selective drivers. Here we review recent developments in systematics, comparative biology, paleontology, synthetic biology, theory, and experimental evolution, highlighting ten selective drivers of simple multicellularity. Our survey highlights the many ecological opportunities available for simple multicellularity, and stresses the need for additional work examining how these first steps impact the subsequent evolution of complex multicellularity.

Human Papillomavirus (HPV) self-sampling has the potential to increase cervical cancer screening (CCS) and reduce the cervical cancer burden in Medically Underserved Women (MUW). However, interventions promoting self-sampling are limited. We examined the effectiveness of an intervention study in increasing CCS among MUW. We conducted a quasi-experimental intervention study. Face-to-face verbal approach was to recruit MUW (n=85, mean age 48.57±11.02) living in a small city in the US. Behavioral intervention based on reframing, reprioritizing, and reforming (3R model) was used to educate the women about CCS in a group format. The women completed pre-and post-intervention assessments and followed-up interviews. The primary outcome was CCS uptake. Mixed methods analyses were conducted using a t-test for the primary outcome, PROCESS for mediation analysis, and NVivo for interview data. Majority of women (75%) completed self-testing. High-risk HPV prevalent among the women was 11%, and of those, 57% followed-up with physicians for care. We found that the significant increase in the women’s post-intervention screening behaviors was mediated by the increase in knowledge (Indirect Effect [IE] = .1314; 95% CI, .0104, .4079) and attitude (IE = .2167; 95% CI, .0291, .6050) scores, (p&lt;0.001). Interview analyses offered further explanations (see the explanations in parenthesis) why MUW found the intervention messages acceptable (encourages proactive behavior), feasible (simple and easy to understand), and appropriate (helpful and informative). Barriers including lack of trust and fear of results were identified. The findings suggest that an intervention that combines the 3R model and self-sampling may increase CCS among MUW.

With the development of industrialization, traditional manufacturing technologies are no longer able to meet the production needs of modern society. Additive manufacturing has successfully solved the problems existing in traditional manufacturing technology. Selective laser melting (SLM) is a powder bed melting technology that produces metal parts by selectively melting metal powders on a platform using a laser beam. It is widely used in additive manufacturing. This article introduces the characteristics and current development status of SLM technology, summarizes the main application fields and common defects of SLM, and finally explores and prospects the future development trend of SLM.

In most industrialized countries, screening programs for cervical cancer have shifted from cytology (Pap smear or ThinPrep) alone on clinician-obtained samples to the addition of screening for human papillomavirus (HPV), its main causative agent. For HPV testing, self-sampling instead of clinician-sampling has proven to be equally accurate, in particular for assays that use nucleic acid amplification techniques. In addition, HPV testing of self-collected samples in combination with a follow-up Pap smear in case of a positive result is more effective in detecting precancerous lesions than a Pap smear alone. Self-sampling for HPV testing has already been adopted by some countries, while others have started trials to evaluate its incorporation into national cervical cancer screening programs. Self-sampling may result in more individuals willing to participate in cervical cancer screening, because it removes many of the barriers that prevent women, especially those in low socioeconomic and minority populations, from participating in regular screening programs. Several studies have shown that the majority of women who have been underscreened but who tested HPV-positive in a self-obtained sample, will visit a clinic for follow-up diagnosis and management. Additionally, a self-collected sample can also be used for vaginal microbiome analysis, which can provide additional information about HPV infection persistence as well as vaginal health in general.

Macro-autophagy is an essential cellular process involved in degradation of aberrant organelles and proteins. Initially proposed to be a ‘bulk’ degradation pathway, a more nuanced appreciation of selective autophagy pathways has emerged in recent years. The discovery of a glycogen-selective autophagy pathway (‘glycophagy’) has highlighted the importance of autophagy in regulating cellular metabolic homeostasis and identified a novel non-canonical major pathway of glycogen flux. The field of glycogen autophagy research is at an early evolutionary stage, but already it is clear that the implications of these discoveries are far-reaching and provide scope for multi-disciplinary investigations into the role of glycophagy in health and disease. With potential cognate protein partners identified, the opportunities for targeted intervention have become viable. Here we review the current evidence relating to specific protein mediators involved in glycophagy, and highlight areas of uncertainty that provide opportunity for further investigation.

The procedures for the extraction and separation of lipids and nutraceutics from microalgae using classic solvents have been used many times. However, these production methods usually require expensive and toxic solvents. Based on our studies involving the use of eco-sustainable methodologies and alternative solvents, we select ethanol (EtOH) and cyclopentyl methyl ether (CPME) for extracting bio-oil and lipids from algae. Different percentage of EtOH in CPME favors the production of an oil rich of SFA useful to production biofuel or rich of compounds bioactive. The proposed method for obtain a rich extract of saturated or unsaturated fatty acids from dry algal biomass is disclosed is eco-friendly and allows a good extraction yield. The method is compared both in extracted oil percentage yield and in extracted fatty acids selectivity to extraction by supercritical carbon dioxide.

Transparent and high-hardness materials have become the object of wide interest. Most notably, it concerns technical glasses and crystals. A notable example is a sapphire – one of the most rigid materials having impressive mechanical stability and good optical properties. Nonetheless, using this material for 3D micro-fabrication is not straightforward due to its brittle nature. On the microscale, selective laser etching (SLE) technology is an appropriate approach for such media. Therefore, we present our research on c-cut crystalline sapphire microprocessing by using femtosecond radiation-induced SLE. Here we demonstrate a comparison between different wavelength radiation (1030 nm, 515 nm, 343 nm) usage for modification inscription and various etchants (Hydrofloridic acid, Sodium Hydroxide, Potassium Hydroxide and Sulphuric and Phosphoric acid mixture) comparison. We show that regular SLE etchants such as Hydrofluoric acid or Potassium Hydroxide are unsuitable materials for selective sapphire laser etching. Meanwhile, a 78% sulphuric and 22% phosphoric acid mixture at 270°C temperature is a good alternative for this process. We present the changes in the material after the separate processing steps. Finally, a protocol for advanced sapphire structure formation and a few exemplary structures are presented.

Several clinically useful anticancer drugs selectively kill cancer cells by inducing DNA damage; the genomic instability and DNA repair defects of cancer cells make them more vulnerable than normal cells to the cytotoxicity of DNA-damaging agents. Because epoxide-containing compounds can induce DNA damage, we have used the MTT assay to evaluate the selective cytotoxicity of three epoxyalkyl galactopyranosides against A549 lung cancer cells and MRC-5 lung normal cells. Compound (2S,3S)-2,3-Epoxydecyl 4,6-O-(S)-benzylidene-β-D-galactopyranoside (EDBGP) showed the highest selective anticancer activity and was selected for mechanistic studies. After observing that EDBGP induced cellular DNA damage (comet assay), we found that cells deficient in nucleotide excision repair were hypersensitive to the cytotoxicity of this compound; this suggests that EDBGP may induce bulky DNA adducts. EDBGP did not inhibit glycolysis (glucose consumption and lactate production). Pre-treatment of lung cancer cells with several antioxidants did not reduce the cytotoxicity of EDBGP, thereby indicating that reactive oxygen species do not participate in the anticancer activity of this compound. Finally, EDBGP was screened against a panel of cancer cells and normal cells from several tissues, including three genetically modified skin fibroblasts with increasing degree of malignancy. Our results suggest that epoxyalkyl galactopyranosides are promising lead compounds for the development of new anticancer agents.

Background: Diabetes is a common non-communicable disease that is responsible for about 9% of all deaths and 25% reduction in life expectancy and nearly half of the diabetic patients are not aware of their disease. In this regard, diabetes screening to identify un-known diabetic patients is of great importance. Aims: The aims of this study were first to evaluate the performance of two commonly used diabetes screening tests that are currently recommended by the Iranian national screening program for diabetes (NSPD). Methods: The validities of the two diabetes screening tests were measured among 1057 participants older than 30 years. The studied screening tests included Capillary fasting blood glucose (CBG) and glycated hemoglobin (HbA1c). The golden standard for measuring the validity of the tests was venous fasting plasma glucose (VPG). Results: According to the results, the sensitivity of CBG and HbA1c tests were 69.01% and 84.5% and the specificity of the tests were 95.7% and 79.3% respectively. Positive and negative predictive values were 53.84% and 97.72% for CBG and 22.72% and 98.61% for HbA1c respectively. The recommended cut-points for CBG and HbA1c were 116.5 mg/dl and 7.15% respectively. Using these values as the new cut-points, sensitivity and specificity of CBG and HbA1c changed to 80.30% and 89.10%, and 77.50% and 94.20% respectively. Conclusions: Compared to several other countries, the performance of NSPD is relatively higher in Iran. ROC analysis suggested new cut-points for significantly better performance of NSPD.

Selective laser melting is an emerging Additive Manufacturing (AM) technology for metals. Intricate three-dimensional parts can be generated from the powder bed by selectively melting the desired location of the powders. The process is repeated for each layer until the part is built. The necessary heat is provided by a laser. Temperature magnitude and history during SLM directly determine the molten pool dimensions, thermal stress, residual stress, balling effect, and dimensional accuracy. Laser-matter interaction is a crucial physical phenomenon in the SLM process. In this paper, five different heat source models are introduced to predict the three-dimensional temperature field analytically. These models are known as steady state moving point heat source, transient moving point heat source, semi-elliptical moving heat source, double elliptical moving heat source, and uniform moving heat source. The analytical temperature model for all of the heat source models are solved using three-dimensional differential equation of heat conduction with different approaches. The Steady state and transient moving heat source are solved using separation of variables approach. However, the rest of models are solved by employing the Green’s functions. Due to the high magnitude of the temperature in the presence of the laser, the temperature gradient is usually high which has a substantial impact on thermal material properties. Consequently, the temperature field is predicted by considering the temperature sensitivity thermal material properties. Moreover, due to the repeated heating and cooling, the part usually undergoes several melting and solidification cycles, this physical phenomenon is considered by modifying the heat capacity using latent heat of melting. Furthermore, the multi-layer aspect of metal AM process is considered by incorporating the temperature history from the previous layer since the interaction of the layers have an impact on heat transfer mechanisms. The proposed temperature field models based on different heat source approaches are validated using experimental measurement of melt pool geometry from independent experimentations. The detailed explanation of the comparison of models is also provided. Moreover, the effect of process parameters on the balling effect is also discussed.

Cervical cancer (CC) is the most common cancer in women worldwide and is almost always associated with repeated infections by human papillomavirus (HPV). Screening by traditional tests combined with biomarker identification techniques for low- or high-grade injuries, are becoming increasingly important in diagnosis and prognosis, avoiding countless deaths. This article explores existing literature on the main serum biomarkers and the identification of biomarkers associated with the oncogenesis of HPV expression in the identification of pre-cancerous lesions and of CC for an effective treatment, with reduction of recurrence, as well as we explain strategies for the development of biomarkers based on DNA, proteins and other markers. We also describe how markers of chromosomal instability host DNA, promoting hypo- or hypermethylation of DNA, as well as polymorphisms and epigenetic events in the p53 gene. Finally, we discuss changes in gene expression using cDNA microarray techniques and changes in the expression of proteins and markers identified through mass spectrometry.

The goal of our study was to identify signatures of selection in the Turopolje pigs and other commercial pig breeds. We conducted a comprehensive analysis of five datasets, including one local pig breed (Turopolje) and four commercial pig breeds (Large White, Landrace, Pietrain, and Duroc), using strict quality control measures. Our final dataset consisted of 485 individuals and 54,075 single nucleotide polymorphisms (SNPs). To detect selection signatures within these pig breeds, we utilized the XP-EHH and XP-nSL methodologies, which allowed us to identify candidate genes that have been subject to positive selection. Our analysis consistently highlighted the PTBP2 and DPYD genes as commonly targeted by selection across all studied breeds. Both of these genes are associated with muscular development in pigs and other species. Furthermore, in the Large White breed a number of genes were detected by the two methods, such as ATP1A1, CASQ2, CD2, IGSF3, MAB21L3, NHLH2, SLC22A15, VANGL1. In Duroc breed a different set of genes was detected, such as ARSB, BHMT, BHMT2, DMGDH, JMY. The function of these genes was related to body weight, production efficiency and meat quality, average daily gain and other similar traits. Overall, our results have identified a number of genomic regionsthat are under selective pressure between local and commercial pig breeds. This information can help to improve our understanding of the mechanisms underlying pig breeding, and ultimately contribute to the development of more efficient and sustainable pig production practices. Our study highlights the power of using multiple genomic methodologies to detect genetic signatures of selection, and provides important insights into the genetic diversity of pig breeds.

Meprin α is a zinc metalloproteinase (metzincin) that has been implicated in multiple diseases, including fibrosis and cancers. It has proven difficult to find small molecules that are capable of selectively inhibiting meprin α, or its close relative meprin β, over numerous other metzincins which, if inhibited, would elicit unwanted effects. We recently identified possible molecular starting points for meprin α-specific inhibition through an HTS effort (see part I, preceding paper). In part II we report the optimization of a potent and selective hydroxamic acid meprin α inhibitor probe which may help define the therapeutic potential for small molecule meprin α inhibition and spur further drug discovery efforts in the area of zinc metalloproteinase inhibition.

Meprin α and β are zinc-dependent proteinases implicated in multiple diseases including cancers, fibrosis, and Alzheimer’s. However, until recently, only a few inhibitors of either meprin were reported and no inhibitors are in pre-clinical development. Moreover, inhibitors of other metzincins developed in previous years are not effective in inhibiting meprins suggesting the need for de novo discovery effort. To address the paucity of tractable meprin inhibitors we developed ultra-high throughput assays and conducted parallel screening of >650,000 compounds against each meprin. As a result of this effort, we identified 5 selective meprin α hits belonging to three different chemotypes (triazole-hydroxyacetamides, sulfonamide-hydroxypropanamides, and phenoxy-hydroxyacetamides). These hits demonstrated a nanomolar to micromolar inhibitory activity against meprin α with low cytotoxicity and >30-fold selectivity against meprin β and other related metzincincs. These are the most selective inhibitors of meprin α to date.

Tandem mass spectrometry (MS/MS) for diagnosing inborn errors of metabolism (IEM) is recognized as an ethical, safe, simple, and reliable screening test. Presented bibliometric analysis aims to describe the network structure of the scientific community in the study area at the level of countries, institutions, authors, papers, keywords, and sources; scientific productivity, directions, and collaboration efforts in a considered period (1991–2023.) Using the PRISMA method, we conducted a systematic search for articles reporting using MS/MS to screen for inherited metabolic disorders and inborn errors of metabolism collected from the Web of Science Core Collection (WOSCC.) A total of 451 articles out of 546, by 2,682 authors, published in 190 journals, with 15,440 citations in 8,181 citing articles, with an average citation of 34.24 per article, and an H-index of 64 were retrieved from the WOSCC. The research status of MS/MS in IEM screening was identified. The most relevant current research directions and future areas of interest were revealed: "selective screening for IEM," "new treatments for IEM," "new disorders considered for MS/MS testing," "ethical issues associated with newborn screening," "new technologies that may be used for newborn screening," "use of a combination of MS/MS and gene sequencing," etc.

Virtual screening - predicting which compounds within a specified compound library bind to a target molecule, typically a protein - is a fundamental task in the field of drug discovery. Doing virtual screening well provides tangible practical benefits, including reduced drug development costs, faster time to therapeutic viability, and fewer unforeseen side effects. As with most applied computational tasks, the algorithms currently used to perform virtual screening feature inherent tradeoffs between speed and accuracy. Furthermore, even theoretically rigorous, computationally intensive methods may fail to account for important effects relevant to whether a given compound will ultimately be usable as a drug. Here we investigate the virtual screening performance of the recently released Gnina molecular docking software, which uses deep convolutional networks to score protein-ligand structures. We find, on average, that Gnina outperforms conventional empirical scoring. The default scoring in Gnina outperforms the empirical AutoDock Vina scoring function on 89 of the 117 targets of the DUD-E and LIT-PCBA virtual screening benchmarks with a median 1% early enrichment factor that is more than twice that of Vina. However, we also find that issues of bias linger in these sets, even when not used directly to train models, and this bias obfuscates to what extent machine learning models are achieving their performance through a sophisticated interpretation of molecular interactions versus fitting to non-informative simplistic property distributions.

Cellular substructure has been widely observed in the sample fabricated by selective laser melting, while its growth direction and the crystallographic orientation have seldom been studied. This research tries to build a general model to construct the substructure from its two dimensional morphology. All the three Bunge Euler angles to specify a unique growth direction are determined, and the crystallographic orientation corresponding to the growth direction is also obtained. Based on the crystallographic orientation, the substructure in the single track is distinguished between cell-like dendrite and cell. It is found that, with the increase of scanning velocity, the substructure transits from cell-like dendrite to cell. The critical growth rate of the transition can be around 0.31 ms^-1.

Abstract: Calcium-based catalysts are of a high interest for glycerol polymerization due to their high catalytic activity and large availability. However, their poor stability under reaction conditions is an issue. In the present study, we investigated the stability and catalytic activity of Ca-hydroxyapatites (HAps) as one of the most abundant Ca-source in nature. A stochiometric, a Ca-deficient and a Ca-rich HAps have been synthetized and tested as catalysts in the glycerol polymerization reaction. Deficient and stochiometric HAps exhibited a remarkable 100% selectivity to triglycerol at 15 % of glycerol conversion at 245 °C after 8 h of reaction in the presence 0.5 mol.% of catalyst. Moreover, under the same reaction conditions, Ca-rich HAp showed a high selectivity (88 %) to di- and triglycerol at a glycerol conversion of 27 %. Most importantly, these catalysts were unexpectedly stable towards leaching under the reaction conditions based on the ICP-OES results. However, based on the catalytic tests and characterization analysis performed by XRD, XPS, IR, TGA-DSC and ICP-OES, we found that HAps can be deactivated by the presence of the reaction products themselves, i.e., water and polymers.

A selection of 36 commercial probiotic fermented dairy products from UK and Europe markets were evaluated for the numbers, types and viability of Lactobacillus strains against the stated information on their packages. A comparative study was carried out on selectivity of MRS-Clindamycin, MRS-Sorbitol and MRS-IM Maltose, to select the right medium for enumeration of probiotic Lactobacillus. Based on selectivity of medium for recovery of the targeted lactobacilli and also simplicity of preparation, MRS-Clindamycin was chosen as the best medium for enumeration of probiotic Lactobacillus in fermented milks. The results of enumeration of lactobacilli showed that 22 out of a total 36 tested products contained more than 106 colony forming units/g at the end of their shelf- life, which comply with the recommended minimum therapeutic level for probiotics. Rep-PCR using primer GTG-5 was applied for initial discrimination of isolated strains, and isolates, which presented different band profile, were placed in different groups. The isolated Lactobacillus spp. were identified mainly as Lactobacillus acidophilus, Lactobacillus casei and Lactobacillus paracasei by analysis of partial sequences of the 16S ribosomal RNA and rpoA genes. In conclusion, it is unknown to recommend the adequate number of probiotic bacteria to be consumed to ensure the beneficial properties.

A study of photovoltaic solar window technologies is reported, focusing on their structural features, functional materials, system development, and suitability for use in practical field applications, e.g. public infrastructures and agricultural installations. Energy generation performance characteristics are summarized and compared to theory-limit predictions. Working examples of pilot-trial solar window-based installations are described. We also report on achieving electric power outputs of about 25 W_p/m² from clear and transparent large-area glass-based solar windows.

4-(thiazol-2-yldiazenyl)phenol (L₁) and 2-((4-hydroxyphenyl) diazenyl)-5-nitrophenol (L₂) based on azo phenol were synthesised and used as selective colorimetric sensor for CN^- and AcO⁻ ion in DMSO/H₂O-HEPES (v/v; 1:1, pH–7.3 ± 0.2) and showed good sensitivity with large red shifts and nanomolar detection limit for CN^- and AcO^- ion. The stoichiometry of L₁ with CN⁻/AcO⁻ ion was found to be 1:1 and L₂ with CN⁻/AcO⁻ ion was found to be 1:2. Binding constant for L₁+ CN⁻, L₁ + AcO⁻, L₂ + CN⁻ and L₂ + AcO⁻ were calculated by B-H plot as 1.6 × 10³, 8.0 × 10², 8.4 × 10³ and 1.7 × 10² respectively. L₂ showed high selectivity towards CN⁻ ion with low detection limit of 81 nM and large binding constant. In addition, ¹H NMR titration and DFT studies also supported the deprotonation mechanism of receptors in the presence of selective anions.

Malassezia species are fastidious and slow-growing yeasts whose isolation from polymicrobial samples is hampered by fast-growing microorganisms. Malassezia selective culture media are needed because Malassezia are resistant to cycloheximide, but some fungi, including the chief human commensal Candida albicans resist to this compound. This study aimed to test whether the macrolide rapamycin could be used in combination with cycloheximide to develop a Malassezia-selective culture medium. Rapamycin susceptibility testing was performed via microdilution assays in modified Dixon against M. furfur and five Candida spp. The MIC was the lowest concentration producing 90% growth inhibition. Rapamycin medium ± cycloheximide 500 mg/L was also added to FastFung solid and yeast suspensions were inoculated and incubated for 72h. Rapamycin MICs against Candida spp. ranged from 0.5 to 2 mg/L, except for C. krusei whose MIC was &gt;32 mg/L. M. furfur stains were rapamycin resistant. Rapamycin and cycloheximide supplementation of the FastFung medium effectively inhibited the growth of non-Malassezia yeast, including the cycloheximide-resistant C. albicans and C. tropicalis. Based on our findings, we recommend using this “MalaSelect” medium for Malassezia isolation and culture from polymicrobial samples.

In standard construction of hyperrational numbers using ultra-power we assume that the ultra lter is selective. It makes possible toassign real value to any nite hyperrational number. So, we can consider hyperrational numbers with selective ultra lter as extension of traditional real numbers. Also proved the existence of strictly monotonic or stationary representing sequence for any hyperrational number.

GS provides exciting opportunities to rapidly identify a diagnosis in critically ill newborns and children with rare genetic conditions. But there are good reasons to remain cautious about the broad implementation of these strategies in babies and children. At best, rapid GS leads to diagnoses in many infants in highly selected populations. It sometimes leads to beneficial and changes in management. Parents and physicians both often find these results useful. We don’t know how useful such testing will be in the general population. It is almost inevitable that genetic counseling will be more challenging in a more general population. We don’t know how often GS helps improve outcome and survival or reduce symptoms in babies who receive a molecular diagnosis. We don’t know the relative cost-effectiveness of whole genome, whole exome, or targeted panels in different populations. We don’t know the relative contribution of a molecular diagnosis to the decision to withdraw life support. Each of these concerns will require careful study of both the technology and the ethical issues to allow us to harness the potential of these new technologies while avoiding foreseeable problems. Studies are underway to see how the tests are used in general populations. These studies should generate important information to guide clinicians and policymakers. In the meantime, parents should know that genetic results sometimes confirm an already suspected dismal prognosis and sometimes yield only ambiguous findings. Anticipatory discussions should try to give parents a realistic understanding of the likely impact of a genetic diagnosis. Both doctors and parents should recognize that the clinical usefulness of diagnostic genomic testing in newborns is a work in progress. We are only a decade into the age of true genomic medicine. We still have much to learn.

New dimers of selected dipyridothiazines with an m-xylene linker have been designed, synthesized and characterized. Their structure was identified using 1H and 13C NMR as well as 2D NMR techniques (COSY, ROESY, HSQC and HMBC experiments) and HR MS spectrometry. The compounds were subjected to preliminary in silico biological profile tests using the Way2Drug server and analysis of the probable cytotoxic effect on various cancer cell lines. Preliminary in vitro cytotoxicity tests were performed against normal cell lines (HaCaT) and five cancer cell lines (SW480, SW620, MDA-MB-231, A-549, LN-229) showing moderate activity. An analysis of the structure-activity relationship was performed.

Dermatoses are essentially due to infectious or free radical aggression, immunoallergic disor-ders, or can be secondary to general diseases. To investigate new antimicrobial sources against dermatoses, Opilia amentacea crude ethanol extracts and fractions were subjected to phytochemical screening and tested for antioxidant and antimicrobial activities on Gram-positive cocci, Gram negative bacilli and fungi. Phytochemical screening revealed secondary metabolites such as sterols, triterpenes, flavonoids and tannins. Leaves and stem bark of Opilia amentacea exhibited the highest total phenolic contain (65,92 ± 0,93 and 65,71 ± 0,57 mg GAE/g DW respectivily) and flavonoids (38,8 ± 1,05 and 26,81 ± 0,19mg QE/g DW respectively). Dichloromethane fractions of leaves (FDFe) and stem bark (FDET) exhibited the best antioxidant activity with FRAP values of 741,15 and 662,84 mMol AAE/g and IC50 values of ABTS of 88,40 and 36,85 µg/mL respectively. These fractions were also the most active on Gram positive bacilli while Hexane leaves (FHFe) and hexane root bark (FHER) fractions exhibited the best antifungal activity against Candida tropicalis at MIC values of 0.23 mg/mL and 0.43 mg/mL respectively. Gram-negative bacteria were particularly resistant. This study constitutes a solid scientific basis that could justify the traditional uses of Opilia amen-tacea as an antidermatosis plant.

Background: As noninvasive prenatal screening usage grows in the general obstetrics setting, proper patient education on the screen’s benefits and limitations is needed. Objective: Describe the use of a technology platform designed for large-scale dissemination of noninvasive prenatal screening information and results. Study Design: The technology platform functioned as follows: Patients were emailed a link to an noninvasive prenatal screening general-education video upon laboratory receipt of a test requisition. Providers were then notified upon availability of patients’ results. If noninvasive prenatal screening results were negative, the patient was sent an automated email with instructions to access results through a secure portal where she could watch tailored informational videos, request “on-demand” or scheduled genetic counseling, or decline any further services. If genetic counseling was elected, a summary of the session was sent to the ordering provider and patient upon completion. If noninvasive prenatal screening results were positive, either the ordering provider or a board-certified genetic counselor contacted the patient directly to communicate test results and provide counseling. The number and type of results issued through the platform, the number and type of genetic counseling consultations completed, and factors associated with requesting laboratory-delivered genetic counseling were tracked and analyzed for a 39-month period. Results: Over the study period, 67,122 noninvasive prenatal screening results were issued through the platform, and 4,673 patients elected genetic counseling consultations; 95.2% (n=4,450) of consultations were for patients receiving negative results. Over 70% (n= 3,370) of consultations were on-demand rather than scheduled. Median consultation time was 14 minutes for positive results and six minutes for negative results. A positive screen, advanced maternal age, family history, previous history of a pregnancy with a chromosomal abnormality, and other high-risk pregnancy were associated with the greatest odds of electing laboratory-delivered genetic counseling. Conclusions: By combining web education, automated notifications, and genetic counseling, we implemented a service that effectively facilitates results disclosure for ordering providers. These data demonstrate the capability to deliver noninvasive prenatal screening results, education, and counseling—congruent with management guidelines—to a large population, which is imperative to quality care as uptake increases.

Embryonic and larval Danio rerio is increasingly used as a toxicological model to conduct rapid in vivo tests and developmental toxicity assays; the zebrafish features as high genetic homology to mammals; robust phenotypes; and its value in high-throughput genetic and chemical screening have made it a powerful tool to evaluate in vivo toxicity. New methodologies of genome editing as CRISPR/Cas9; ZFN or Talen make it a suitable model to perform studies to pair human genetic diseases as well. This review surveys recent studies; employing zebrafish as experimental model; comparing it with other in vivo and in vitro models; presenting zebrafish as a potent vertebrate tool to evaluate drug toxicity to facilitate more extensive; easy and comprehensive knowledge of new generation drugs.

(1) Background: Hepatitis C virus (HCV) screening mostly uses a one-assay anti-HCV testing approach, which has a higher probability of false-positive results in populations with low HCV prevalence. (2) Methods: In this investigation, 17,926 participants, were screened for HCV, and the reactives were tested using a two-assay anti-HCV approach: Elecsys ElectroChemiLuminescence (ECL) and a ChemiLuminescence ImmunoAssay (CLIA), respectively. A recombinant immunoblot assay (RIBA) was performed to confirm anti-HCV positivity. Statistical analysis was performed. (3) Results: A total of 350 specimens resulted reactive in the ECL screening, of which CLIA retesting showed that 292 (83.4%) were anti-HCV reactive (283 positive, 9 indeterminate, none negative by RIBA), but 58 (16.6%) were not anti-HCV reactive (15 positive, 12 indeterminate, 31 negative by RIBA). The two-assay strategy significantly improved the positive predictive value (PPV: 95.00%) with χ2: 7.59(p&lt;0.01) then the PPV assessed by one assay (PPV: 90.6%) with χ2: 34.51 (p&lt; 0.001). The ROC curve defined a sensibility and specificity for the dual approach of: 99.66% and 100.00%. (4) Conclusions: Compared with a one-assay testing strategy, the two-assay testing strategy may significantly reduce false positives in anti-HCV testing and identify inactive HCV infection in low seroprevalence populations.

Marine microalgae are a rich reservoir of natural compounds, including bioactives. Nonetheless, these organisms remain fairly unexplored despite their potential biotechnological applications. Culture collections with diverse taxonomic groups and lifestyles are a good source to unlock this potential and discover new molecules for multiple applications such as the treatment of human pathologies or the production of aquaculture species. In the present work extracts from 33 strains (including 20 dinoflagellates, 4 diatoms and 9 strains from other 7 algal classes), cultivated under identical conditions were examined for antiviral, antibacterial, anti-inflammatory and anti-cancer activities. Among these, antiviral and anti-inflammatory activities were detected in a few strains while antibacterial tests showed positive results in most assays. In turn, most trials did not show any anti-cancer activity. Wide differences were observed between species within the same class, in particular dinoflagellates which were better represented in this study. These preliminary findings pave the way for in-depth characterization of extracts with highest signals in each test, identification of compounds responsible of the biological activities found, and a further screening of the CCVIEO culture collection.

COVID-19 patients suffer from detrimental effects of cytokine storm and not much success has been achieved to overcome this issue. We sought to test the ability of selenium in reducing the impact of two important cytokine storm players; IL-6 and TNF-a. The effects of four selenium compounds were evaluated on the secretion of these cytokines from THP-1 macrophages in vitro following LPS challenge. Also, potential impact of methylseleninic acid (MSeA) on Nrf2 and IkBa was determined following short treatment of THP-1 macrophages. MSeA was observed to be the most potent selenium form to reduce IL-6 and TNF-a levels among the four selenium compounds tested. In addition, an increase in Nrf2 and decrease in pIkBa in human macrophages was observed following MSeA treatment. Our data indicate that COVID-19 patients might benefit by suppressing their cytokine storm with addition of MSeA to the standard therapy.

The illicit use of fentanyl has led to hundreds of thousands of opioid-related deaths worldwide. Therefore, the detection of fentanyl by law enforcement and recreational users is of utmost importance. However, current detection methods are expensive, time-consuming, require special storage conditions and necessitate complex instrumentation that is generally unportable and requires skilled personnel to operate. An alternative approach would be using molecularly imprinted polymers (MIPs) as the recognition component of a handheld sensor, testing strip, or color-based assay. In this work, a molecularly imprinted polymer was made by using methacrylic acid (MAA) and ethyleneglycol dimethacrylate (EGDMA) as the functional monomer and cross-linking monomer respectively, and benzylfentanyl (Bfen) as the template. The use of benzylfentanyl is advantageous because it closely resembles the structure of fentanyl but does not have any physiological effects as a narcotic. Important studies herein determined the optimum ratio of the template:functional monomer, with subsequent evaluations of selectivity versus the commonly encountered narcotics such as heroin, cocaine, and methamphetamine. The data obtained from the HPLC analysis showed that the Bfen-MIP was successful in selectively binding the template and actual fentanyl, better than other common narcotics.

Selective laser sintering (SLS) has drawn attention for the fabrication of three-dimensional oral dosage forms due to the plurality of drug formulations that can be processed. The aim of this work was to employ SLS with a CO2 laser for the manufacturing of carvedilol personalised dos-age forms of various strengths. Carvedilol (CVD) and vinylpyrrolidone-vinyl acetate copolymer (Kollidon VA64) blends of various ratios were sintered to produce CVD tablets of 3.125, 6.25 and 12.5 mg. The tuning of the SLS processing parameter laser intensity, improved printability and impacted the tablet hardness, friability, CVD dissolution rate, and the total amount of drug re-leased. Physicochemical characterization showed the presence of CVD in the amorphous state. X-ray micro-CT analysis demonstrated that the applied CO2 intensity affected the total tablet po-rosity, which was reduced with increased laser intensity. The study demonstrated that SLS is a suitable technology for the development of personalised medicines that meet the required specifications and patient needs.

Given the rise in the number of cases and their recurrences, Urinary Tract Infections (UTI) are one of the major burdens on public healthcare worldwide. Rapid, inexpensive and selective detection of Uropathogenic E. coli (UPEC), a major contributor to UTIs, is the need of the hour for effective treatment, given the rise of antibiotic-resistant bacteria due to improper diagnosis. Here we present a rapid, real-time, selective and label-free detection of UPEC using an integrated sensing platform based on Crossed Surface Relief Gratings (CSRGs) as nanoplasmonic sensors. Detection is achieved due to the unique Surface Plasmon Resonance (SPR)-based light energy exchange attributed to the CSRGs, allowing real-time sensing in a very narrow bandwidth of the incident light to pass where the SPR energy conversion occurs. The sensing ability of the platform is experimentally demonstrated by the detection of bulk Refractive Index (RI) changes, with a bulk sensitivity of 382.2 nm/RIU and a resolution in the order of 10-6 RIU. We demonstrate selective capture and detection of clinical concentration of UPEC, as opposed to other gram-negative bacteria, in real-time, a first for CSRGs. This work is particularly important for effective treatment of UTIs, allowing point-of-care diagnosis for economically disadvantaged regions around the world.

The aim of this study was to investigate the possibility of a freeform fabrication of porous ceramic parts through selective laser sintering (SLS). SLS was proposed to manufacture ceramic green parts because this additive manufacturing technique can be used to fabricate three-dimensional objects directly without a mold, and the technique has the capability of generating porous ceramics with controlled porosity. However, ceramic printing has yet fully achieved its 3D fabrication capabilities without using polymer binder. Except for the limitation of high melting point, brittleness and low thermal shock resistance from instinct ceramic material properties, the key hurdle lies on very poor absorptivity of oxide ceramics to fiber laser which is widely installed in the commercial SLS equipment. An alternative solution to overcome the poor laser absorptivity via improving material compositions was presented in this study. The positive effect of carbon additive on the absorptivity of silica powder to fiber laser will be discussed. To investigate the capabilities of the SLS process, 3D porous silica structures were successfully prepared and characterized.

Introduction: The combination of Virtual Screening (VS) techniques with in vivo screening in the zebrafish model is currently being used in tandem for drug development in a faster and more efficient way. Areas covered: We review the different virtual screening techniques, the use of zebrafish as a vertebrate model for drug discovery and the synergy that exists between them. Expert opinion: We highlight the advantages of combining virtual and zebrafish larvae screening for drug discovery. On the one hand, VS is a faster and cheaper tool for searching active compounds and possible candidates for therapy than in vivo screening when processing large compound libraries. On the other hand, zebrafish larvae form a vertebrate model which allows in vivo screening of large amounts of the compounds. Importantly physiology and chemical response are mostly conserved between zebrafish and mammals. The availability of the transgenic and mutant zebrafish lines allows an analysis of a specific phenotype upon treatment along with toxicity, off-target effect, side effects, and dosage. Advantages of VS, in vivo whole animal approach screening, and the screening combinations are also reviewed.

During the last decade, the demand for lithium has been growing exponentially with its widespread uses in manufacturing, especially with the worldwide deployment of electric vehicles. Thus, lithium is considered integral to the U.S. economy, technological advancement, and the pursuit of sustainable and clean energy solutions. The produced water is known to be rich in several minerals and valuable elements, such as potassium and magnesium, and a trace amount of precious elements including lithium. However, the existence of metals in the produced water is one of the challenges to extract lithium, especially magnesium which is located in diagonal positions within the periodic table that exhibit similarities. The produced water was first purified, resulting in the complete removal of magnesium, and then lithium was precipitated by phosphate. The effects of operating conditions on the Li₃PO₄ precipitation behaviors were evaluated. The effect of different precipitating reagents was evaluated on the percentage of lithium extracted, Na₃PO4 (TSP) was found to be a promising Li precipitating reagent. The highest percentage of lithium extracted was reached when the Li concentration of produced water was enriched and increased up to 350 mg/l, then Li removal was 53% at 7 grams of TSP and 200 rpm for 2 hours. The results indicated that temperature is a more important factor than stirring speed. The novelty of the current work is not only by the results obtained that may create additional financial benefits to oil-producing areas but on that the sustainable disposal of produced water may encourage the recycling and reuse practice, ultimately reducing the use of freshwater for hydraulic fracturing.

Porcine sapovirus (PoSaV) is a significant pathogen causing diarrhea with high morbidity and mortality rates. Given its zoonotic characteristics, this study conducts a comprehensive genetic evolutionary analysis of PoSaV. Results confirmed PoSaV as the primary RNA virus in piglet feces (27.54%). Phylogenetic analysis identifies the prevalent PoSaV strain SHCM/Mega2023 in the GIII genogroup, involving a recombinant event with MK962338 and KT922089. The time tree revealed that the GIII genogroup exhibits the widest divergence time span, indicating a high likelihood of viral recombination. Further selective pressure calculations demonstrate that PoSaV was under purifying selection (dN/dS &lt; 1), with seven positively selected sites in VP1 protein which might be related to the antigencity. In conclusion, this study presents a novel genomic evolution of PoSaV, offering valuable insights into antigenicity and vaccine research.

There is a fast-growing interest in the use of selective laser melting (SLM) for metal/alloy additive manufacturing. Our current knowledge of SLM printed 316 stainless steel (SS316) is limited and sometimes appears sporadic, presumably due to the complex interdependent effects of a large number of process variables of the SLM processing. This is reflected from the discrepant findings in the crystallographic textures and microstructures in this investigation with those reported in the literatures, which also vary itself. The as-printed material is macroscopically asymmetric in both the structures and crystallographic textures. The <101> and <111> crystallographic directions align parallel with the SLM scanning direction (SD) and build direction (BD), respectively. Like-wise, some characteristic low angle boundary features are reported crystallographic, while this investigation unequivocally proves them non-crystallographic since they always maintain an identical alignment with the SLM laser scanning direction irrespective of the matrix material’s crystal orientation. There is also 500±200 nm columnar or cellular features, depending on the cross-section, generally found all over the sample. These columnar or cellular features are formed with walls made of dense packing of dislocations entangled with Mn, Si and O enriched amorphous inclusions. They remain stable after the ASM solution treatments at 1050 °C temperatures, and therefore, are capable of hindering boundary migration events of recrystallization and grain growth. Thus, the nanoscale structures can be retained at high temperatures. Large 2-4 µm inclusions form during the solution treatment, within which the chemical and phase distribution are heterogeneous.

The goal of the next generation World Wide Web is machine readability through linked databases. To improve web search, integration, and mining in local languages like Urdu, there is a growing need to develop ontologies and vocabulary in these languages. The majority of people use the web in local languages for agriculture, social media interaction, news, etc. How to create agents for the integration of web data. In our country, the literacy ratio is very low and IT literacy is negligible. More comprehensive information for its target audience is only possible through the World Wide Web. Our first target is to improve and enhance the use of social media and the web in local languages. That will encourage its constructive use in Urdu for society and the economy. The Web in natural languages is the source of income for small and medium enterprises. The semantic web is concerned with linked databases and structured data. In this work, we are focused on some selected ontologies to be translated into natural languages. Expertise in Ontology Engineering helps us in job production. Ontology Engineering has extensive freelancing opportunities. Only if the web is correctly interpreted in regional languages is an economic boost achievable. A standardized foundation for data sharing and reuse on the internet is provided by the Semantic Web. In other words, a group of standards and technology that enables computers to comprehend the semantics (meaning) of material on the Web.

A Zn(II) perchlorate complex has been prepared and characterized by single X-ray crystallography, nuclear magnetic resonance spectroscopy, thermogravimetric analysis, infrared spectroscopy, elemental analysis, and UV-vis spectroscopy. The complex crystallizes in the monoclinic space group P21/c (Z = 4) with a pentacoordinated zinc center. Interestingly, the Zn complex was found be to a potential fluorophore that could sense acetone and other ketones with high selectivity and sensitivity.

Temperature field is an essential attribute of metal additive manufacturing in view of its bearings on the prediction, control, and optimization of residual stress, part distortion, fatigue, balling effect, etc. This work provides an analytical physics-based approach to investigate the effect of scan strategy parameters including time delay between two irradiations and hatching space on thermal material properties and melt pool geometry. This approach is performed through the analysis of the distribution of material properties and temperature profile in three-dimensional space. The moving point heat source approach is used to predict the temperature field. To predict the temperature field during the additive manufacturing process some important phenomena are considered. 1) Due to the high magnitude of temperature in the presence of the laser, the temperature gradient is usually high which has a crucial influence on thermal material properties. Consequently, the thermal material properties of stainless steel grade 316L are considered to be temperature-dependent. 2) Due to the repeated heating and cooling, part usually undergoes several melting and solidification cycles. This physical phenomenon is considered by modifying the heat capacity using the latent heat of melting. 3) The multi-layer aspect of metal AM process is considered by incorporating the temperature history from the previous layer since the interaction of the successive layers has an impact on heat transfer mechanisms. 4) Effect of heat affected zone on thermal material properties is considered by the superposition of material properties in regions where the temperature fields of two consecutive irradiations have an overlap since the consecutive irradiations change the behavior of the material properties. The goals are to 1) investigate the effects of temperature-sensitive material properties and constant material properties on the temperature field. 2) Study the behavior of thermal material properties under different scan strategies. 3) Study the importance of considering the effect of heat affected zone on thermal material through the prediction of melt pool geometry. 4) Investigate the effect of hatching space on melt pool geometry. This work is purely employed physics-based analytical models to predict the behavior of material properties and temperature field under different process conditions, and no finite element modeling is used.

Organic compounds that contain poly-triazole are very important intermediates in pharmaceutical and chemical industry. Click chemistry is one of essential reactions that can form C-N bond with high atom economy. The research progress in metals catalyzed Click chemistry of azides and alkynes from the perspective of reaction mechanism is categorized and summarized.

The recovery of precious metals is a project with both economic and environmental significance. In this paper, it presents how to use bacterial mineralization to selectively recover gold from multi-ionic aqueous systems. The Bacillus licheniformis FZUL-63, separated from a landscape lake in FuZhou University, was shown to selectively mineralize and precipitate gold from coexisting ions in aqueous solution. The removal of Au(III) was almost happened in first hour, and FTIR data show that the amino, carboxyl and phosphate groups on the surface of the bacteria are related to the adsorption of gold ions. XPS results implied that Au(III) ions are reduced to monovalent, and then the Au(I) was adsorbed on the bacterial surface at the beginning stage(first hour). XRD results showed the gold biomineralization began about 10 hours after the interaction between Au(III) ions and bacteria. The Au(III) mineralization has been rarely influenced by other co-existing metal ions. TEM analysis shows the gold nanoparticles are polyhedral structure with a particle size of ~20 nm. The Bacillus licheniformis FZUL-63 could selectively mineralize and recover 478 mg/g(dry biomass) gold from aqua regia-based metal wastewater through four cycles. It could be of great potential in the practical application.

Using nanoindentation under various strain rates, the mechanical properties of a selective laser melted (SLM) SKD61 at the 800 mm/s scan speed was investigated and compared to SLM H13. No obvious pile-up due to the ratio of the residual depth (h_f) and the maximum depth (h_max) being lower than 0.7 and no cracking were observed on any of the indenter surfaces. The nanoindentation strain-rate sensitivity (m) of SLM SKD61 was found to be 0.034, with hardness increasing from 8.65 GPa to 9.93 GPa as the strain rate increased between 0.002 s⁻¹ and 0.1 s⁻¹. At the same scan speed, the m value of SLM H13 (m = 0.028) was lower than that of SLM SKD61, indicating that the mechanical behavior of SLM SKD61 was more critically affected by the strain rate compared to SLM H13. SLM processing for SKD61therefore shows higher potential for advanced tool design than for H13.

In this article/review, the selective interactions of several berberine and palmatine derivatives with various DNA G-quadruplex structures are reported. These derivatives were constructed starting from two natural compounds, berberine and palamatine, through specific synthetic passages following two different schemes for each of them and using several substituents. The details of these synthesis are also described. Indeed, the study of the interactions of these derivative compounds with various G-quadruplex forming sequences was carried out by means of various structural and biochemical techniques. The results show that the presence of suitable side chains are very useful to improve the interaction of the ligands with G-quadruplex structures. Thus, since G-quadruplex formation is promoted by these compounds, which have never been reported before, these may be tested as potential anticancer drugs.

It is of great significance to develop sustainable processes of catalytic reaction. We report an efficient and selective procedure for the synthesis of acetylated bioactive compounds in water. The use of 1-acetylimidazole combined with Er(OTf)₃ as Lewis acid catalyst gives high regioselectivity and good to excellent yields for the acetylation of primary hydroxyl groups as well as amino groups. The protection is achieved in short reaction times under microwave irradiation and is successful even in the case of base-sensitive substrates.

The up-and-coming microfluidic technology is the most promising platform for designing anti-cancer drugs and new point-of-care diagnostics. Compared to conventional drug screening methods based on Petri dishes and animal studies, drug delivery in microfluidic systems has many advantages. For instance, these platforms offer high throughput drug screening, require a small amount of samples, provide an in vivo-like microenvironment for cells, and eliminate ethical issues associated with animal studies. Multiple cell cultures in microfluidic chips could better mimic the 3D tumor environment using low reagents consumption. The clinical experiments have shown that combinatorial drug treatments have a better therapeutic effect than monodrug therapy. So many attempts were performed in this field in the last decade. This review highlights the applications of microfluidic chips in anti-cancer drug screening and systematically categorizes these systems as a function of sample size and combination of drug screening. Finally, it provides a perspective on the future of the clinical applications of microfluidic systems for anti-cancer drug development.

Purpose: Expanded carrier screening (ECS) informs couples of their risk of having offspring affected by certain genetic conditions. Limited data exists assessing the actions and reproductive outcomes of at-risk couples (ARCs). We describe the impact of ECS on planned and actual pregnancy management in the largest sample of ARCs studied to date. Methods: Couples who elected ECS and were found to be at high risk of having a pregnancy affected by at least one of 176 genetic conditions were invited to complete a survey about their actions and pregnancy management. Results: Three hundred ninety-one ARCs completed the survey. Among those screened before becoming pregnant, 77% planned or pursued actions to avoid having affected offspring. Among those screened during pregnancy, 37% elected prenatal diagnostic testing (PNDx) for that pregnancy. In subsequent pregnancies that occurred in both the preconception and prenatal screening groups, PNDx was pursued in 29%. The decision to decline PNDx was most frequently based on the fear of procedure-related miscarriage, as well as the belief that termination would not be pursued in the event of a positive diagnosis. Conclusions: ECS results impacted couples’ reproductive decision-making and led to altered pregnancy management that effectively eliminates the risk of having affected offspring.

To screen and validate immunosuppressive factors in luminal- and basal-like breast cancer cell lines and tissue samples associated with malignant phenotypes. The mRNA microarray datasets, GSE40057 and GSE1561, were downloaded and remodelled. Differentially expressed genes (DEGs) were identified. Enrichment analyses performed and the online resources, GOBO and Kaplan-Meier Plotter, were employed to screen for immunosuppressive factors associated with breast cancer malignant phenotypes. qRT-PCR and western blot were used to validate the expression of CD274 and IL8 in cell lines and immunohistochemical detected the MIF and VEGFA on tissue microarrays. The results showed that CD274 and IL8 were both upregulated in basal-like cell lines. That MIF expression was dramatically increased in patients with breast cancer metastases (p<0.05) and that VEGFA expression positively correlates with breast cancer pathologic grade (p<0.05).During the formation and development of breast cancer, immune-related genes are always activated, and immunosuppressive factors CD274, IL8, MIF and VEGFA are upregulated. Such molecules could be used as biomarkers for breast cancer prognosis. However, because individual immune-related factors can play several biological roles, the mechanistic relationship between immunosuppressive factors and breast cancer malignant phenotypes and the feasibility of their application as drug targets require further investigation.

The voltage-gated potassium channel KV1.3 has been recognized as a tumor marker and represents a promising new target for the discovery of new anticancer drugs. We designed a novel structural class of KV1.3 inhibitors through structural optimization of benzamide-based hit compounds and structure-activity relationship studies. The potency, and selectivity of the new KV1.3 inhibitors were investigated using whole-cell patch- and voltage-clamp experiments. 2D and 3D cell models were used to determine antiproliferative activity. Structural optimization resulted in the most potent and selective KV1.3 inhibitor 44 in the series with an IC50 value of 470 nM in oocytes and 950 nM in Ltk cells. Kv1.3 inhibitor 4 induced significant apoptosis in Colo-357 spheroids, while 14, 37, 43, and 44 significantly inhibited Panc-1 proliferation.

Since the UK commenced newborn screening for isovaleric acidemia in 2015, changes in prescribing have increased the incidence of false positive (FP) results due to pivaloylcarnitine. A review of screening results between 2015-22 identified 24 true positive (TP) and 84 FP cases, with pivalate interference confirmed in 76/84. Initial C5 carnitine (C5C) did not discriminate between FP and TP with median (range) C5C of 2.9 (2.0 - 9.6) and 4.0 (1.8 - &gt;70) µmol/L respectively and neither did Precision Newborn Screening via Collaborative Laboratory Integrated Reports (CLIR), which identified only 1/47 FP cases. However, among the TP cases, disease severity showed a correlation with initial C5C, in ‘asymptomatic’ individuals (n=17), demonstrating a median (range) C5C of 3.0 (1.8 – 7.1) whilst ‘clinically affected’ patients (n=7), showed a median (range) C5C of 13.9 (7.7 - &gt; 70) µmol/L. These findings allowed the introduction of dual cut-off values into the screening algorithm to reduce the incidence of FPs, with initial C5C results ≥ 5 µmol/L triggering urgent referral, and those &gt; 2.0 and &lt; 5.0 µmol/L prompting 2nd tier C5-isobar testing. This will avoid delayed referral in babies at particular risk whilst reducing the FP rate for the remainder.

Lipid nanoparticles (LNPs) are promising carriers for constructing drug delivery systems (DDSs) in disease treatments. Previous studies have suggested that lipid composition and biophysical properties of LNPs can significantly impact their interaction with cells and tissues, allowing for the development of suitable LNPs for precise drug delivery. Our previous study proposed the concept and facile preparation of reconstituted lipid nanoparticles (rLNPs), which not only have the advantages of traditional LNPs but also contain the lipids of mother cell/tissue. In this study, we have found that brain-derived rLNPs (B-rLNPs) can have much better accumulation to the ischemic area of the ischemic stroke (IS) model than liver-derived rLNPs (L-rLNPs). This homing effect hopefully makes rLNPs a useful tool for developing highly accessible devices with homologous targeting ability for precise drug delivery.

The adsorption of supramolecular composites for Cs(I) in high level liquid waste (HLLW) are different due to different carriers. We chose 25,27-bis(ethyl)-calix[4]arene-26,28-crown-6 (EC[4]C6) as adsorbent, SiO2-P, XAD-7 and UiO-66 as carriers. The synthesis and characterization of supramolecular EC[4]C6 loaded with three different carriers were presented. SEM, N2 adsorption/desorption isotherms, TG-DSC spectra, FT-IR spectra results shown that EC[4]C6 was successfully introduced into the pores of carriers via physical intermolecular interactions. EC[4]C6/SiO2-P, EC[4]C6/XAD-7 and EC[4]C6/UiO-66 shown high efficiency, high selectivity towards Cs(I) over 18 typical fission or corrosion products in HNO3 solution. The adsorption properties of the three materials were investigated after electron irradiation. These results demonstrate that EC[4]C6/SiO2-P possess greater potential for highly efficient removal of Cs(I) from HLLW.

Degradation of intracellular components through autophagy is a fundamental process to maintain cellular integrity and homeostasis. Recently a glycogen-selective autophagy pathway has been described, termed ‘glycophagy’. Glycogen is a primary storage depot and regulator of glucose availability, and glycophagy is emerging as a critical physiological process involved in energy metabolism. Glycophagy-mediated degradation of glycogen appears to operate in parallel with the well-described canonical pathway of glycogenolysis involving glycogen phosphorylase. Evidence suggests that starch-binding domain protein-1 (Stbd1) is a key glycogen-binding protein involved in tagging glycogen for glycophagy, and that Gabarapl1 is primarily involved as the Atg8 family protein recruiting the Stbd1-glycogen complex into the forming glycophagosome. The nuances of glycophagy protein machinery, regulation and lysosomal glucose release are yet to be fully elucidated. In this mini-review, we critically analyze the current evidence base for glycophagy as a selective-autophagy process of physiological importance and highlight areas where further investigation is warranted.

This article describes an algorithm for estimation the variance of Gaussian noise. The data is smoothed using the Savitsky-Golay polynomial filter. Absolute differences between original and smoothed data are sorted in ascending order. The initial part of this sequence is selected for analysis. The result of calculation mean value of differences can be used to estimate the variance of the noise. By selecting points for analysis, the impact of cosmic ray noise and other artifacts can be reduced. The use of the proposed method for artificial and real spectra shows the ability to effectively estimate the noise variance. The algorithm contains no user-defined parameters.

Bauxite residue (BR) is a well promising resource for critical metals and especially scandium (Sc), a rare and expensive metal with increasing applications in advanced technology. Particularly, Greek BR’s composition indicates a sound possibility for a commercially viable recovery of Sc under the conditions of an optimized leaching process and the subsequent use of advanced separation techniques. Leaching with mineral acids emerges as the dominant selection with comparison to other techniques. This study investigates an optimized leaching condition set on Sc recovery, using sulfuric acid as the most suitable among different acids tested, in the context of process economics and environmental constraints. Several variables were studied individually or combined in order to achieve high Sc concentration in the leachate as well as to ensure selectivity, especially in respect to iron. The most significant parameters proved to be the solid to liquid ratio (S/L), the final pH value as well as the use of recycling of leachate on fresh BR batches. The proposed process, using sulfuric acid at low acid molarities under ambient conditions was integrated rapidly leading to high and selective Sc recovery. A flow diagram of the developed leaching process in industrial scale was proposed based on continuous operation.

The thorough description of the peculiarities of additively manufactured structures represents a current challenge for aspiring freeform fabrication methods, such as the selective laser melting (SLM). All of which have an immense advantage in the fast fabrication (no special tooling or moulds required), the geometrical flexibility in the design of components, and their efficiency when only low quantities are required. However, designs demand the precise knowledge of the material properties, which in case of additively manufactured structures are anisotropic and, under certain circumstances, in addition of an inhomogeneous nature. Furthermore, these characteristics are highly dependent on the fabrication settings. Within this study, the anisotropic tensile properties of selective laser melted stainless steel (1.4404, 316L) are investigated: The Young’s modulus ranged from 148 GPa to 227 GPa, the ultimate tensile strength from 512 MPa to 699 MPa and the breaking elongation ranged, respectively, from 12% to 43%. The results were compared to related studies, in order to classify the influence of the fabrication settings. Furthermore, the influence of the chosen raw material was addressed by comparing deviations on the directional dependencies reasoned by differing microstructural developments during manufacture. Stainless steel was found to possess its maximum strength at a 45° layer versus loading offset, which is precisely where AlSi10Mg was previously reported to be at its weakest.

Vit-106 is a promising zirconium-based alloy with high glass-forming ability and belongs to the so-called bulk metallic glasses (BMG). Workpieces with a size of around one centimeter in all three dimensions can be obtained from a BMG alloy by casting. However, further increasing the cast size decreases the cooling rate and thus induces crystallization. Selective laser melting (SLM) is a well-known technique to overcome the size limitations for BMGs because a workpiece is built by the addition of multiple melt portions where the cooling rate is kept above the critical one. Currently, BMG parts obtained by SLM suffer from partial crystallization. The present work studies the influence of SLM process parameters on partial crystallization of Vit-106 by metallography and the influence of the microstructure on mechanical properties by microhardness and wear resistance testing. Submicron crystalline inclusions are observed in an amorphous matrix of Vit-106 alloy obtained by SLM. The size and the concentration of the inclusions can be controlled by varying the laser scanning speed. It is shown that submicron crystalline inclusions formed in the amorphous matrix during SLM can favorably affect microhardness and wear resistance.

The valley pseudospin properties of electrons in two–dimensional hexagonal materials result in lots of fascinating physical phenomena, which opens up the new field of valleytronics. The valley-contrasting physics aims at distinguishing the valley degree of freedom based on valley–dependent effects. Here, we theoretically demonstrate that both of the valley–selective high harmonic generation and valley–selective electronic excitation can be achieved by using an orthogonal two–color (OTC) laser field in gapped graphene. It is shown that the asymmetry degrees of harmonic yields in the plateaus, cutoff energies of generated harmonics and electron populations from two different valleys can be precisely controlled by the relative phase of the OTC laser field. Thus the selectivity of the dominant valley for the harmonic radiation and electronic polarization can be switched by adjusting the relative phase of the OTC laser field. Our work offers an all–optical route to produce the valley–resolved high harmonic emissions and manipulate the ultrafast valley polarization on a femtosecond timescale in condensed matter.

The military taxonomy of class indices for chemical and biological warfare agents considers halogenated tear agents (CS) to be incapacitating causing local pain and discomfort with associated reflexe. The removal yield of the organic substances present in the water depends on the environmental conditions, on the chemical composition of the water and on the chemical substance dissolved in the water, which constitutes the substrate of the metabolic activities of the microorganisms that use these substances in the biochemical reactions of the cellular enzyme complexes. The two -CN groups in the malonic nitrile molecule are strongly electron-attracting and activate the CH2 group to which they are linked, and because of this, malononitrile has the role of a methylene component in condensation reactions with aldehydes or ketones. The results obtained after analyzing the degree of hydrolysis in the samples that contained the biological suspension indicated that no CBM metabolites were detected in any biological sample, regardless of the test concentration, analyzed 24 h after incubation. In the parallel samples, the aqueous solutions of CBM without biological treatment had metabolites in the samples., at 30 minutes the degree of hydrolysis is 0.21%, at 60 minutes, the degree of hydrolysis is 5.42%, after 90 minutes, the degree of hydrolysis is 6.19%, and after 24 hours. the degree of hydrolysis is 23.41%. Chemical substances in contact with microorganisms are used by them in the biochemical processes in which they are involved, the retention time and biodegradation capacity have led to an increased effect of the metabolism of toxic substances, in metabolic reactions, organic substances are the source of carbon and energy for biochemical processes. The tests performed indicate that the suspension of Chlorella sp. consumed the entire amount of CBM and metabolites from the analyzed samples The tests prove that the biological material can be used for the decontamination of the affected areas.

Selective Paste Intrusion (SPI) is an additive manufacturing (AM) process in which thin layers of aggregates are selectively bonded by cement paste only where the structure is to be produced. In this way, concrete elements with complex geometries and structures can be created. Reinforcement is required to increase the flexural strength of the concrete elements and, thus, enable their applicability in practice. Integrating the reinforcement is a difficult task, particularly in the case of SPI due to the layer-wise printing method. Especially with respect to possible complex structures, the production of the reinforcement needs to be adapted to SPI, thereby offering a high degree of freedom. One concept for a reinforcement integration is combining the two additive manufacturing processes SPI and Wire and Arc Additive Manufacturing (WAAM). However, since the two processes serve different fields of application, their compatibility is not necessarily given. Ongoing investigations show that the temperatures caused by WAAM adversely affect both, the cement paste rheology required for sufficient paste penetration into the particle bed and the overall concrete strength. This paper provides an overview of ongoing research focusing on different cooling strategies and their effects on the compressive strength of SPI-printed concrete parts.

The sustainability of the planet and its inhabitants is in dire danger and is among the highest priorities on global agendas such as the Sustainable Development Goals (SDGs) of the United Nations (UN). Solar energy -- among other clean, renewable, and sustainable energies -- is seen as essential for environmental, social, and economic sustainability. Predicting solar energy accurately is critical to increasing reliability and stability, and reducing the risks and costs of the energy systems and markets. Researchers have come a long way in developing cutting-edge solar energy forecasting methods. However, these methods are far from optimal in terms of their accuracies, generalizability, benchmarking, and other requirements. Particularly, no single method performs well across all climates and weathers due to the large variations in meteorological data. This paper proposes SENERGY (an acronym for Sustainable Energy), a novel deep learning-based auto-selective approach and tool that, instead of generalising a specific model for all climates, predicts the best performing deep learning model for GHI forecasting in terms of forecasting error. The approach is based on carefully devised deep learning methods and feature sets through an extensive analysis of deep learning forecasting and classification methods using ten meteorological datasets from three continents. We analyse the tool in great detail through a range of metrics and methods for performance analysis, visualization, and comparison of solar forecasting methods. SENERGY outperforms existing methods in all performance metrics including Root Mean Square Error (RMSE), Mean Absolute Error (MAE), Mean Absolute Percentage Error (MAPE), Forecast Skills (FS), Relative Forecasting Error, and the normalised versions of these metrics. The proposed auto-selective approach can be extended to other research problems such as wind energy forecasting and predict forecasting models based on different criteria (in addition to the minimum forecasting error used in this paper) such as the energy required or speed of model execution, different input features, different optimisations of the same models, or other user preferences.

The glycosaminoglycan, heparan sulphate (HS), orchestrates many developmental processes. Yet its biological role has not yet fully been elucidated. Small molecule chemical inhibitors can be used to perturb HS function and these compounds pro-vide cheap alternatives to genetic manipulation methods. However, existing chemical inhibition methods for HS also interfere with chondroitin sulphate (CS), complicating data interpretation of HS function. Herein, a simple method for the selective inhibition of HS biosynthesis is described. Using endogenous metabolic sugar pathways, Ac4GalNAz produces UDP-GlcNAz, which can target HS synthesis. Cell treatment with Ac4GalNAz resulted in defective chain elongation of the polymer and decreased HS expression. Conversely, no adverse effect on CS production was observed. The inhibition was transient and dose-dependent, affording rescue of HS expression after removal of the unnatural azido sugar. The utility of inhibition is demonstrated in cell culture and in whole or-ganisms, demonstrating that this small molecule can be used as a tool for HS inhibition in biological systems.

The energy transfer process of laser selective melting is very complex. To study the effect of la-ser selective melting on the microstructure and properties of 18Ni-300 martensitic steel, ABAQUS was used to simulate the temperature of laser cladding 18Ni-300 martensitic steel at different time points and different laser power. The results show that the cross-section shape of the molten pool changes from round to oval With the increase of laser power, the higher the peak value of temperature time curve, the greater the temperature gradient; and the laser clad-ding experiment of 18Ni-300 martensitic steel was carried out, and the microstructure and me-chanical properties of the samples under different laser power were analyzed. The results show that with the increase of laser power, the grain size of the cladding layer becomes smaller and the microstructure becomes more compact; the hardness of the side surface of the sample is higher than that of the upper surface, and the tensile strength and elongation show a trend of first increasing and then decreasing.

A rapid and appropriate genetic and metabolic acclimation, which is crucial for plants’ survival in a changing environment, is maintained due to the coordinated action of plant hormones and cellular degradation mechanisms influencing proteostasis. The plant hormone abscisic acid (ABA) rapidly accumulates in plants in response to environmental stress and plays a pivotal role in the reaction to various stimuli. Increasing evidence demonstrates a significant role of autophagy in controlling ABA signaling. This field has been extensively investigated and new discoveries are constantly being provided. We present updated information on the components of the ABA signaling pathway, particularly on transcription factors modified by different E3 ligases. Then, we focus on the role of selective autophagy in ABA pathway control and review novel evidence on the involvement of autophagy in different parts of the ABA signaling pathway that are important for crosstalk with other hormones, particularly cytokinins and brassinosteroids.

Although the concept of additive manufacturing has been proposed for several decades, momentum of selective laser melting (SLM) is finally starting to build. In SLM, density and surface roughness, as the important quality indexes of SLMed parts, are dependent on the processing parameters. However, there are few studies on their collaborative optimization in SLM to obtain high relative density and low surface roughness simultaneously in the previous literature. In this work, the response surface method was adopted to study the influences of different processing parameters (laser power, scanning speed and hatch space) on density and surface roughness of 316L stainless steel parts fabricated by SLM. The statistical relationship model between processing parameters and manufacturing quality is established. A multi-objective collaborative optimization strategy considering both density and surface roughness is proposed. The experimental results show that the main effects of processing parameters on the density and surface roughness are similar. It is noted that the effects of the laser power and scanning speed on the above objective quality show highly significant, while hatch space behaves an insignificant impact. Based on the above optimization, 316L stainless steel parts with excellent surface roughness and relative density can be obtained by SLM with optimized processing parameters.

Breast cancer remains a major public health concern, and early detection can result in more treatment options, which are crucial for improving survival rates. Metabolomics offers the potential to develop blood-based screening and diagnostics tools that are less invasive and more cost-effective. However, the inherent complexity of metabolomic datasets makes identifying the most diagnostically relevant biomarkers a difficult task, with multiple studies demonstrating lim-ited agreement on the specific metabolites and pathways involved. This study aims to identify a set of biomarkers for early diagnosis of breast cancer using metabolomics data. Plasma samples from 185 breast cancer patients and 53 controls (CHTN) were analyzed. We utilized univariate Naïve Bayes, L2-regularized Support Vector Machines, and Principal Component Analysis (PCA), along with feature engineering techniques, to select the most informative features. Multiple ma-chine learning models, including Support Vector Machines, Multidimensional Scaling, Logistic Regression, and Ensemble Learning were utilized for classification. The best-performing feature set comprised 4 biomarkers and 2 demographic variables, achieving an accuracy of 98%, demon-strating the potential for a robust, cost-effective, non-invasive breast cancer screening and diagnostic tool.