The incidence of diabetes mellitus (DM) continues to rise worldwide and one of the most serious microvascular complications is diabetic kidney disease (DKD), which is the leading cause of end-stage renal disease. Current bi-omarkers such as urinary albumin excretion rate have limitation for early detection of DKD. In our study we used ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-QTOF-ESI+-MS) techniques to quantify previously analyzed metabolites, such as tryptophan, kynurenic acid, taurine, l-acetylcarnitine, glycine, and tiglylglycine. We performed the targeted analy-sis of metabolites from urine and serum samples, collected from 110 subjects. Of these, 90 patients with type 2 DM (T2DM) were divided according to the urinary albumin/creatinine ratio (UACR) into normoalbuminuria 300 mg/g groups, respectively, while 20 subjects were rep-resented by healthy controls. Through various validation methods, we identified several metabolites as potential biomarkers, such as kynurenic acid, glycine, and l-tryptophan in serum and l-acetylcarnitine, tiglylglycine, and tau-rine in urine.

Exosomes are small extracellular vesicles produced by almost all cell types in the human body and exosomal microRNAs (miRNAs) are small non-coding RNA molecules that are known to serve as important biomarkers for diseases such as cancer. Given that the upregulation of miR-106b is closely associated with several types of malignancies, the sensitive and accurate detection of miR-106b is important but difficult. In this study, a surface acoustic wave (SAW) biosensor was developed to detect miR-106b isolated from the cancer cells based on immunoaffinity separation technique using our unique paddle screw device. Our novel SAW biosensor could detect a miR-106b concentration as low as 0.024 pM in a linear range from 0.1 pM to 1.0 μM with a correlation coefficient of 0.9939. Additionally, we were able to successfully detect miR-106b in total RNA extracted from the exosomes isolated from the MCF-7 cancer cell line, a model system for human breast cancer, with performance comparable to commercial RT-qPCR methods. Therefore, the exosome isolation by paddle screw method and the miRNA detection using the SAW biosensor has the potential to be used in basic biological research and clinical diagnosis as an alternative to RT-qPCR.

Colorectal cancer (CRC) is a weighty cause of mortality worldwide, with growing incidence in the Middle East. Understanding the level of awareness about CRC screening among the Syrian pop-ulation is crucial public health interventions. A cross-sectional study was conducted from Sep-tember 22, 2023, to October 15, 2023, involving 928 participants from six major governorates in Syria. An online questionnaire containing socio-demographic, knowledge, and attitude sections was used to collect data. Descriptive statistics and chi-square tests were employed for data analysis using (SPSS) v28.0. The survey revealed a lack of awareness regarding CRC screening among the Syrian population, with only 499(53%) of the proportion demonstrating adequate knowledge about the disease and its screening methods. Significant associations were observed between the level of knowledge and socio-demographic factors including gender, work status, and economic status (p < 0.05). The findings emphasize the need for public health initiatives to enhance awareness and knowledge about CRC and its early screening methods in Syria. Education is essential for improving early detection and reducing the burden of colorectal cancer in the region. Efforts to increase public understanding of CRC screening are critical for reducing the incidence and mortality.

This narrative review delves into the evolving landscape of fertility preservation techniques with a particular focus on their use in patients undergoing oncology treatment that carries a risk of ovarian insufficiency. Advances in established methods such as cryopreservation of oocytes and embryos are highlighted and the increasing use of gonadotropin-releasing hormone (GnRH) agonists is discussed. The review also addresses the complexities and controversies associated with these approaches, such as the 'flare-up' effect associated with GnRH agonists and the potential of GnRH antagonists to reduce the risk of ovarian hyperstimulation syndrome. Despite advances in fertility preservation, the report highlights the challenges we face, including the need for personalized treatment protocols and management of associated risks. It calls for continued research and collaboration between healthcare professionals to refine these techniques and ultimately improve reproductive outcomes for patients facing the prospect of fertility-impairing treatment.

Aerobic glycolysis in cancer cells, originally observed by Warburg 100 years ago, which involves production of lactate as the end product of glucose breakdown even in the presence of adequate oxygen, is the foundation for the current interest in cancer cell-specific reprograming of metabolic pathways. The renewed interest in cancer cell metabolism has now gone well beyond the original Warburg effect related to glycolysis to other metabolic pathways to include amino acid metabolism, one-carbon metabolism, pentose phosphate pathway, nucleotide synthesis, antioxidant machinery, etc. Since glucose and amino acids constitute the primary nutrients that fuel the altered metabolic pathways in cancer cells, the transporters that mediate the transfer of these nutrients and their metabolites not only across the plasma membrane but also across the mitochondrial and lysosomal membranes have become an integral component of expansion of the Warburg effect. In this review, we focus on the interplay between these transporters and metabolic pathways that facilitates the metabolic reprogramming which has become the hallmark of cancer cells. The beneficial outcome of this recent understanding of the unique metabolic signature surrounding the Warburg effect is the identification of novel drug targets for development of a new generation of therapeutics to treat cancer.

SMARCA4-deficient non-small cell lung cancer (NSCLC) is a more recently recognized subset of NSCLC. We describe the 18F-fluorodeoxyglucose (FDG) PET/CT findings in a rare case of SMARCA4-deficient NSCLC and response to therapy. A 45-year-old male patient with a history of heavy smoking (10 years) underwent an 18F-fluorodeoxyglucose (FDG) PET/CT dynamic (chest) + static (whole-body) scan for diagnosis and pre-treatment staging. 18F-FDG PET/CT showed an FDG-avid mass in the upper lobe of the left lung (SUVmax of 22.4) and FDG-avid lymph nodes (LN) in the left pulmonary hilar region (SUVmax of 5.7). In addition, there are multiple metastases throughout the body, including distant LNs, adrenal glands, bone, and brain. Pathological findings confirmed SMARCA-4 deficient NSCLC. After 4 cycles of chemotherapy and immune checkpoint inhibitors（ICI）, the patient underwent again an 18F-FDG PET/CT scan (including dynamic scan) for efficacy evaluation. We report cases that deepen the understanding of the 18F-FDG PET/CT presentation of SMARCA4-deficient NSCLC as well as dynamic imaging features and parametric characteristics.

Background: Excessive sun exposure, together with insufficient protection, is the main risk factor for the onset of Melanoma and Non Melanoma skin cancer, namely the most common cancer in fair-skinned populations across the world, and of several other skin and eye adverse health effects. Epidemiological data show the existence of scant awareness of this risk, and of high rates of sunburn among young people. The main aim of the present study is to examine sun exposure habits and protection behaviour in university students. Methods: We performed a cross-sectional questionnaire-based study to investigate sun exposure and protection practices in a group of education sciences students at a university in southern Spain. This survey provided data for a descriptive and comparative analysis, by groups and gender, of photoprotection and skin self-examination practices. The reliability and validity of the questionnaire have been analysed. Results: The questionnaire was completed by 315 students. Most of them (74.6%) have suffered at least one sunburn in the last year. The use of sunscreen or protective clothing is not frequent, and 89.5% of students do not self-examine their skin. The metric properties of the questionnaire showed high values of reliability and validity. Conclusions: The awareness of solar exposure risk in Spanish university students of Education Sciences is low, self-protection is scant, the potential exposure to dangerous levels of UV radiation is high and most students have suffered one or more sunburns in the last year. Intervention strategies should be introduced in these students to highlight the risks involved and the need of more adequate sun protection practices. Information campaigns should be conducted to address the problem so that, when these students become teachers, they have an adequate knowledge of the risk and of the benefits of a higher attention to this problem, and can translate these competences in health education.

Background and Aim: Cancer is a disease characterized by uncontrolled cell growth and invasion of tissues. It seems that personality differences and psychological factors are important factors that lead to different reactions to cancer. Therefore, the main purpose of the present study was to investigate the relationship between type D, stress level of life events, personality traits, and anxiety sensitivity in people with breast cancer attending to Tehran Bu-ali Hospital. Methods: The study was a correlational study in which 100 cancer patients referred to Bu-ali Hospital in Tehran, selected by the available sampling method from April to June 2018. The tools used included the Denollet DS-14 Type D Questionnaire, the Paykel Life events Questionnaire, the Eysenck Personality Questionnaire, the ASI Anxiety Scale, Floyd et al., Data analysis in this study is taken place by using SPSS software, two descriptive levels (percentage, frequency, etc.) and regression. Results: The study results showed that there is a relationship between type D personality with stress of life events, neurosis, extraversion, and psychopath dimensions of personality and anxiety sensitivity in breast cancer patients. Conclusion: Psychological factors play a role in the incidence and exacerbation of breast cancer, and ultimately patients with personality type D and personality traits such as psychosis and high anxiety sensitivity and more stress of life events show more symptoms.

Deploying Cellular Internet of Things (CIoT) devices in urban and remote areas faces significant energy efficiency challenges. This is especially true for Narrowband IoT (NB-IoT) devices, which are expected to function on a single charge for up to 10 years while transmitting small amounts of data daily. The 3rd Generation Partnership Project (3GPP) has introduced energy-saving mechanisms in Releases 13 to 16, including Early Data Transmission (EDT) and Preconfigured Uplink Resources (PUR). These mechanisms extend battery life and reduce latency by enabling data transmission without an active Radio Resource Control (RRC) connection or Random Access Procedure (RAP). This paper examines these mechanisms using the LENA-NB simulator in the ns-3 environment, which is a comprehensive framework for studying various aspects of NB-IoT. The LENA-NB has been extended with PUR, and our analysis shows that PUR significantly enhances battery life and latency efficiency, particularly in high-density environments. Compared to the default RAP method, PUR reduces energy consumption by more than 2.5 times and increases battery life by 1.6 times. Additionally, PUR achieves latency reductions of 2.5-3.5 times. The improvements with PUR are most notable for packets up to 125 bytes. Our findings highlight PUR’s potential to enable more efficient and effective CIoT deployments across various scenarios. This study represents a detailed analysis of latency and energy consumption in a simulated environment, advancing the understanding of PUR’s benefits.

Adolescence is a central phase for the development of a person’s identity involving complex multidimensional changes and increasing vulnerability to distress. The aim of this study was to investigate the psychological well-being of adolescent students in Brescia (Northern Italy), two years after the beginning of the Covid-19 pandemic. An online survey investigated the extent and the reasons reported by high school students for their emotional distress (ED), also considering other factors such as physical activity, diet, sleep and smartphone overuse. The main reasons for ED were classified through a qualitative analysis of the freetext answers. 1686 students agreed to participate, 50% showed a presence of ED. According to a multiple logistic analysis, the main factors associated to ED were female gender (AdjOR 2.3, p<0.0001), age (AdjOR 1.6, p<0.0001), sleep duration <8 hours (AdjOR 1.5, p=0.0003), anxiety perception (AdjOR 3.4, p<0.0001), and certain eating behaviors, e.g. comfort food consumption (AdjOR 2.0, p<0.0001). According to free-text answers, the main reasons for ED were: “school pressure”, “ relationships with family and peers”, “negative emotional states” and “the pandemic”. The results show a high level of ED among adolescents and the reported reasons may help to better address their psychological needs after the pandemic.

Radial nerve palsies present a challenging clinical scenario, often leading to substantial functional impairment. This study focuses on evaluating the outcomes of tendon transfer surgeries in patients with post-traumatic radial nerve injuries. The radial nerve, vital for upper limb movements, faces various etiologies such as trauma, compression, or idiopathy. Patients with radial nerve palsy encounter difficulties in daily activities, emphasizing the need for effective management strategies. The research introduces a novel evaluation protocol, aiming to comprehensively assess tendon transfer outcomes. This protocol incorporates functional movements of wrist and finger joints, encompassing both objective and subjective parameters. The retrospective study includes eleven patients treated between 2010 and 2022, with a minimum follow-up of one year post-surgery. Tendon transfers demonstrated positive results. The evaluation protocol covers a wide range of parameters, including wrist and finger mobility, thumb function, grip strength, and patient satisfaction. The results indicate successful restoration of motor function, with an average grip strength of 70% compared to the healthy arm. The proposed evaluation protocol facilitates standardized and reproducible assessment, minimizing subjective errors in clinical evaluations. Despite the study's limitations, such as a relatively small sample size, the findings underscore the effectiveness of tendon transfers in treating radial nerve palsies. The introduced evaluation scheme provides a comprehensive and reproducible approach to assess outcomes, contributing to the global standardization of tendon transfer assessments in radial nerve injuries.

Background: Bariatric surgery (BS) has a significant impact on body composition (BC) and con-sequently may affect established sarcopenic obesity (SO) in candidate patients. The aim of this study is to assess the utility of muscle ultrasound (MUS) of rectus femoris thickness (RFT) for the evalua-tion of BC and skeletal muscle function in patients undergoing BS compared to bioimpedance analysis (BIA), dual-energy X-ray absorptiometry (DEXA) and dynamometry. On the other hand, we aim to demonstrate how MUS of RFT correlates better with the quality of life (Qol) in this population, likely because it enables the detection of regional quadriceps muscle sarcopenia, in comparison to the other mentioned methods. Methods: This is a prospective pilot study including 77 subjects (64.9% female, mean age: 53.2 ± 8.67 years) who underwent BS. Handgrip strength was measured using a dynamometer, fat-free mass index (iFFM) was assessed by BIA, appendicular muscle index (AMI) was calculated using DEXA and RFT was measured by MUS. Moreover, Homeostasis Model Assessment of Insulin Resintance (HOMA-IR) was calculated. All these measurements were conducted 1 month prior to BS and at the 12-month follow-up. QoL was as-sessed using the Moorehead-Ardelt questionnaire. Results: The mean BMI decreased by 12.95 ± 3.56 kg/m2 (p=0.001). Firstly, we observed positive correlation pre-surgery between HOMA and: RFT (r=0.27, p=0.02), iFFM (r=0.36, p=0.001), AMI (r=0.31, p=0.01) and dynamometer (r=0.26, p=0.02). In addition, we found correlation between RFT and iFFM (pre-surgical: r=0.31, p=0.01; post-surgical: r=0.25, p=0.05) and between RFT and lower extremities AMI post-surgical (r=0.27, p=0.04). Secondly, we observed significant reductions in iFFM, AMI and RFT (p=0.001), but not with dynamometer (p=0.94). Finally, a tendency to a positive correlation between QoL question-naire and RFT post-surgery (r=0.23, p=0.079) was observed. Conclusions: Our results suggest that RFT measured by MUS for the evaluation of SO and the follow-up after BS of these patients. Moreover, RFT can provide relevant information about regional sarcopenia and probably has an accurate correlation with QoL in comparison with the other methods.

The decarbonization of the electricity grid as one among the actions to reduce fossil fuel emissions, and thus their impact on global warming in the future, will be achieved mainly via the integration and widespread diffusion of renewable power sources. This is going to be supported also by the shift from the paradigm production-transmission-distribution, where electricity production oversees large-size power plants, to renewable-based distributed/diffused production, where electricity is generated very close or even by the same (group of) user(s) (or prosumers in the latter case). The number of mid-/small-size installations based on renewable energy technologies will therefore increase substantially, and the related renewable generation will be dominant against that from large-size power plants. Unfortunately, this will reduce the reliability of the grid very likely, unless appropriate countermeasures are taken/implemented, hopefully at the same time the paradigm shift is being achieved. To this aim, it is important to identify the anomalies and main fault causes that might determine in renewable-based power systems. This paper surveys the current state-of-the-art on anomalies and faults affecting wind-PV-storage hybrid power systems, i.e., the main renewable technology ensemble that will establish the future grid, and highlights possible research directions that may help to fill the literature gaps.

The sustainable development of resource-based cities has long been a focal point for both governmental policies and academic research. A wealth of academic literature identifies the 'resource curse' as a critical barrier to sustainable development in these urban areas. Despite extensive studies, a consensus on effective strategies to circumvent or resolve this challenge remains elusive. Recent empirical data reveals a noticeable pattern of economic growth differentiation in China's resource-based cities. Why do some resource-based cities experience economic decline while others achieve sustainable economic growth? Therefore, this paper analyzes the reasons for the divergence of economic growth in resource cities from the perspective of heterogeneity. The results of the study show that the phenomenon of the resource curse is conditional, and the heterogeneity of demo-graphic changes, geographic location and institutional environment has a significant impact on the economic growth of resource cities. These factors are investigated to elucidate the observed diversification and heterogeneity in the economic growth of resource-based cities. Building upon this analysis, the paper proposes a framework for differentiated sustainable development pathways tailored to the unique contexts of these cities. This approach not only contributes to the current understanding of the 'resource curse' but also offers novel insights for future research aiming to adopt a more nuanced and context-specific perspective in examining sustainable urban development.

The objective of this study is to determine the relationship between body condition score (BCS) and body carcass fat (BCF) of ewes at two key stages of the production cycle. Data were collected from 88 Coopworth ewes including BCS measurements manually evaluated by the farm manager, BCF measurements determined by computerized tomography (CT) and body parameter measurements automatically determined by an image processing application. Artificial neural network (ANN) statistical analysis method was used to develop a relationship between the body parameters and the BCF with an r2=0.96 and RMSE=1.01 using all top and side variables.

Aiming at the problems of high labor intensity and high cost of manual picking, high loss rate of mechanical picking seeds, low mechanization level and difficult to guarantee the quality of picking plates in the process of picking plates of edible sunflower. Based on the principle of manual plate taking, a plate taking control system for sunflower harvesting table was designed. Through the research and analysis of the principle of taking the plate of the edible sunflower harvesting table. According to the actual operation requirements, the overall scheme of the sunflower plate control system is determined, and the control strategy of imitating artificial low loss harvesting is designed. To reduce the grain loss in the process of taking the plate and improve the control accuracy of the system on the movement speed and displacement of the key components in the process of taking the plate, a trapezoidal acceleration and deceleration control algorithm is designed as the control algorithm of taking the plate. To verify the working performance of the plate control system, with the absolute error, relative error and total loss rate of the harvest as objectives. The bench and field verification experiments were both carried out. The bench experiment showed that the speed error of the plate parts was not more than 0.028 m/s. In the bench experiments of the device, the maximum positioning error was 1.25 mm, the average relative error is only 0.94 %, and the grain loss rate was not more than 2.26 %. It result showed that the system algorithm was reliable, the positioning accuracy was high, and the taking plate operation can be completed well. The field verification experiment showed that the forward speed of the unit was in the range of 0.4~0.8 m/s, and the total loss rate of harvest was less than 5 %. When the forward speed is 0.6 m/s, the minimum harvest loss rate is 2.32 %, and which indicated the control system meets the requirements of sunflower harvesting operation.

Accurately estimating shrub biomass in arid and semi-arid regions is critical for understanding ecosystem productivity and carbon stocks at both local and global scales. However, capturing the shrub biomass accurately by satellite observations is challenging due to the short and sparse features of shrubs. In this study, we presented a framework to estimate shrub biomass at a 10m spatial resolution by integrating ground in-situ data, unmanned aerial vehicle (UAV), Sentinel-2, and Sentinel-1 observations. The pilot study was conducted in the Helan mountains of Ningxia province, China. First, the spatial distribution map of shrubland and other land cover types was generated in 2023. Then, a prediction model of shrub biomass was developed in a Random Forest Regression (RFR) approach driven by different predicted variable datasets based on in-situ measurements, UAV, and satellite images. Finally, the developed model was used to produce the biomass map of shrubland in 2023. The uncertainty was characterized by creating a standard deviation (SD) map using the Leave-One-Out Cross-Validation (LOOCV) method in the shrub biomass estimates. The resultant shrubland distribution map in 2023 has an F1 score of 0.92. The shrub biomass model driven by spectral bands and vegetation indices (R2= 0.62) demonstrated superior performance than that only driven by spectral bands (R2=0.33) or vegetation indices (R2=0.55). The uncertainty of the estimated biomass was lower than 4%, with the lowest values (<2%) happening in the high shrub coverage (>30%) and biomass production (>30kg/m2) regions. Furthermore, the findings show that the magnitude of shrub biomass was affected by the aridity and precipitation significantly in the study region. This study provides a workflow to accurately monitor the biomass of shrublands in a complicated environment based on remote sensing images from multi-platform observations.

Background: Ankle fractures, comprising about 10% of musculoskeletal injuries, pose a significant healthcare burden with an increasing incidence, particularly among an aging population. This study focuses on isolated Danis-Weber type B fractures. Recent trends lean towards surgical intervention for anatomical restoration, quicker recovery, albeit with associated complications. This report aims to assess the safety and efficacy of NewClip narrow locking plate system with early weight bearing in treating isolated fibular fractures. Methods: The study includes patients with Danis-Weber type B fractures surgically treated with NewClip narrow locking plate system. Exclusions involved nondisplaced fractures, open fractures, or those requiring additional fixation.Results: Fifteen patients were enrolled in this study. Minor complications, including wound swelling, were observed in two cases. The Visual Analogue Scale (VAS) for pain exhibited a steady decline postoperatively, with almost complete resolution by the third month. At three months, the FAOS demonstrated excellent results, and final follow-up at twelve months revealed complete osseous healing without complications.Conclusions: The use of this type of plates in treating isolated fibular fractures with early weight bearing shows promising results in terms of fracture healing, pain resolution, and functional outcomes warranting further investigation with larger cohorts.

In light of the critical and emerging global challenge posed by the increasing frequency and severity of heatwaves in recent decades, this study demonstrates a practical and robust workflow that bridges the gap in understanding how the effective integration of remote sensing data with ground-based observations can facilitate a comprehensive assessment of spatiotemporal heatwave patterns and trends in the central region of Thailand. This research transcends traditional methods, utilizing air temperature (Tair) and satellite-derived land surface temperature (LST) data from 1981 to 2019. Results exhibit that an analysis of Tair indicates increasing daytime heatwaves in peri-urban areas, with significant trends in heatwave number (HWN), heatwave frequency (HWF), and heatwave duration (HWD), heatwave amplitude (HWA) rises in urban settings while nighttime heatwaves significantly intensify in rural locales. Notably, LST trends reveal varied patterns, with peri-urban areas showing marked daytime increases in heatwave magnitude (HWM), HWA, and HWF. Correlation analysis (p=0.05) highlights strong daytime associations between Tair and LST in rural (HWN, HWF, HWD, r&gt;0.90) and peri-urban (HWM, HWA, r&gt;0.65) regions. Overall, this study advances approaches to the adaptable measurement and spatial-temporal pattern of heatwave-related risk areas, providing insights for decision-makers to develop sustainable practices and strategies for climate change adaptation.

Precise individual tree or sample-based inventories derived from 3D point cloud data of mobile laser scanning can improve our comprehensive understanding of the structure, function, resilience, biodiversity, and ecosystem services of urban forests. This study assessed the performance of a hand-held laser scanning system for the extraction of tree position, diameter at breast height (DBH) and tree height (H) in an urban area. A total of 2083 trees of 13 species from 34 plots were analyzed. The results showed that the registration of tree positions using ground control points (GCPs) demonstrated high accuracy, with errors consistently below 0.4 m, except for a few instances. The extraction accuracy of DBH for all trees and individual species remained consistently high, with a total root mean square error (RMSE) of 2.06 cm (6.89%) and a bias of 0.62 cm (2.07%). Notably, broad-leaved trees outperformed coniferous trees, with RMSE and bias values of 1.86 cm (6%) and 0.76 cm (2.46%) compared to 2.54 cm (9.46%) and 0.23 cm (0.84%). Tree height extraction accuracy varied significantly among different species, with R2 values ranging from 0.65 to 0.92. Generally, both DBH and height were underestimated. Linear mixed effects models (LME) were applied to evaluate factors affecting the performance of HLS with the plot as a random factor. LME analysis revealed that plant type and terrain significantly influenced the accuracy of DBH and H derived from HLS data. Other fixed factors of plot area, tree density and trajectory length didn’t have significance. With a large sample size, we concluded that the HLS demonstrated sufficient accuracy in extracting individual tree parameters in urban forests.

In March 2013, a novel avian influenza A H7N9 virus was emerged in China, which cause rapidly progressive pneumonia and with a high fatality rate. Serologic studies to evaluate neutralizing antibodies of infected patients and birds are invaluable tools for immunogenicity research of H7N9 and epidemiological investigation. Conventional neutralization assays are laborious and time-consuming which also hampered by biosafety requirement. In this study, We construct and produce pseudovirus bearing the full-length hemagglutinin (HA) of H7N9 virus in the Env-defective, luciferase-expressing HIV-1 backbone. The production of lentiviral pseudovirus was analysed by HA gene specific real-time reverse-transcription PCR, transmission electron microscopy (TEM), and Western Blot assay to prove the nucleic acid replication, the morphology of virus, and the expression of HA protein in pseudovirus. After that pseudovirus based inhibition assay was established to detect neutralizing antibodies of a panel of serum samples. Our results demonstrated that H7N9 pseudovirus which had single-cycle infection was generated. By comparing the neutralization antibody titers, pseudovirus based neutralization test could be recognized as an alternative of conventional microneutralization (MN). Hence, we conclude that it is possible to use pseudovirus inhibition assay to screen sera samples, as well as evaluate vaccine-induced neutralizing antibodies against H7N9 virus.

The advancement of performance in the domain of flexible wearable strain sensors has become increasingly significant due to extensive research on laser-induced graphene (LIG). An innovative doping modification technique is required owing to the limited progress achieved by adjusting laser parameters to enhance LIG’s performance. By pre-treating with AgNO3, we successfully manufactured LIG with a uniform dispersion of silver nanoparticles across its surface. The experimental results for the flexible strain sensor exhibit exceptional characteristics, including low resistance (183.4 Ω), high sensitivity (426.8), a response time of approximately 150 ms, and a relaxation time of about 200 ms. Moreover, this sensor demonstrates excellent stability under various tensile strains and remarkable repeatability during cyclic tests lasting up to 8,000 s. Additionally, this technique yields favorable results in finger bending and hand back stretching experiments, holding significant reference value for preserving the inherent characteristics of LIG preparation in a single-step and in situ manner.

Bigeye grunt Brachydeuterus auritus is an important economic species in the waters off Sierra Leone in West Africa, with great ecological value. Based on the survey data of bottom trawl nets from 6 voyages from 2019 to 2021, the body weight-length relationship (WLR), as well as their relative fatness, were studied in depth using the method of body length and its corresponding mean body weight. This study fitted the WLR of bigeye grunt by gender, calculated its fullness, and analyzed the influence of environmental factors. The results showed that month and gender had a significant impact on body length and weight distribution (P&lt;0.01). There was a highly significant negative correlation (P&lt;0.01) between the condition factor (a) and the allometric factor (b) in the WLR, and salinity significantly affects b (P&lt;0.05). The (lga)/b ratio was less affected by environmental factors which may be related to the body size and density of the fish. The difference in b between male and female populations was extremely significant (P&lt;0.01). The relative fatness had significant seasonal variation characteristics, with highly significant effects of sex and body length (P&lt;0.01). With increasing body length, the relative fatness showed two types of changes, continuously increasing and first increasing then decreasing, with salinity and b significantly affecting the type of change (P&lt;0.05) and depth having a highly significant effect (P&lt;0.01). The bigeye grunt off the coast Sierra Leone exhibited significant seasonal growth characteristics, with significant differences in growth characteristics between male and female individuals. This study suggested that salinity may be the main factor affecting its growth and development. In addition, this study hypothesised that the peak breeding season may occur during the dry season, beginning in December and ending before April of the following year. The study provides updated and more comprehensive insights into the biology and ecology of the bigeye grunt offshore Sierra Leone, West Africa, which can provide scientific basis for its resource assessment, development and utilization, and resource management.

We have carried out a systematic review of the scientific literature published on PM and, more specifically, on its presence in fish and seafood of interest to the population from Mediterranean area. Given its preference and wide acceptability in the scientific community, we followed the PRISMA. The potential functional and clinical toxicity in humans due to MP in fish must be considered by the chemical composition of the microplastics the presence of PM and its additives, associated contaminants and pathogens in fish and shellfish, as well as the possible effects on human health, requires improving legislation on evaluation and providing a basis for consumer protection.

Background and Objectives: The purpose of this study was to investigate whether early surfactant administration affects the status of ductus arteriosus (DA) in preterm infants ≤32 weeks of gestational age (GA) within 24 hours of birth. Materials and Methods: It is a prospective study conducted from March 15, 2022, to November 15, 2023, in a tertiary academic center. In-born infants ≤ 32 weeks of gestation (n = 88) were enrolled. The study group was further divided into surfactant (n=44) and non-surfactant (n=44) subgroups. Results: 76% of the preterm infants who received surfactant therapy (RRR = 0.839) recorded an increase in Kindler Score at 24 hours of life (1-RR = 1-0.24 = 76%). Surfactant administration was significantly associated with decreased pre-ductal diastolic pressure (29.9 mmHg vs. 34.8 mmHg, p=0.0231), post-ductal diastolic pressure (28.7 mmHg vs. 32.2 mmHg, p=0.0178) pre-ductal MAP (41.6 mmHg vs. 46.5 mmHg, p=0.0210) post-ductal MAP (41.0 mmHg vs. 45.3 mmHg, p=0.0336). There were no significant changes in ductus arteriosus parameters at 24 hours of life. Conclusions: Early surfactant administration does not affect the status of ductus arteriosus in preterm infants ≤32 weeks of gestational age at 24 hours of life.

In this study, we investigated the features of co-infection with SARS-CoV-2 and nonpathogenic strain LEV8 of coxsackievirus A7 or enterovirus A71 for Vero E6 cells and Syrian hamsters. The investigation of co-infection with SARS-СoV-2 and LEV-8 or EV-A71 in the cell model was shown that a competitive inhibitory effect for these viruses were especially significant against SARS-CoV-2. Pre-infection with enteroviruses in animals caused more than a 100-fold decrease in the levels of SARS-CoV-2 virus replication in the respiratory tracts and more rapid clearance of the lower respiratory tract from infectious SARS-CoV-2. Co-infection with SARS-CoV-2 and LEV-8 or EV-A71 also reduced the severity of clinical manifestations of the SARS-CoV-2 infection for animals. Additionally, the histological data illustrated that co-infection with nonpathogenic coxsackievirus decreased the level of pathological changes by SARS-CoV-2 in the lungs. Research into the chemokine/cytokine profile demonstrated that the studied enteroviruses efficiently triggered this part of antiviral immune response, which can be associated with significant inhibition of SARS-CoV-2 infection. These results demonstrate that there exists a strong viral interference between the studied nonpathogenic strain of coxsackievirus A7 or enteroviruses A71 and SARS-CoV-2 pathogenic for humans in vitro and in vivo.

A method based on ultra performance liquid chromatography with diode array detector (UPLC-DAD) was developed for quantitative analysis of five active compounds and chemical fingerprint analysis of Rosa rugosa. Ten batches of Rosa rugosa collected from different plantations in the Xinjiang region of China were used to establish the fingerprint. The feasibility and advantages of the used UPLC fingerprint were verified for its similarity evaluation by systematically comparing chromatograms with professional analytical software recommended by State Food and Drug Administration (SFDA) of China. In quantitative analysis, the five compounds showed good regression (R²=0.999 5) within the test ranges and the recovery of the method was in the range of 94.2–103.8%. The similarities of the fingerprints of 10 batches of the samples were more than 0.981. The developed UPLC fingerprint method is simple, reliable and validated for the quality control and identification of Rosa rugosa. Additionally, simultaneous quantification of five major bioactive ingredients in the Rosa rugosa samples was conducted to interpret the consistency of the quality test. The results indicated that the UPLC fingerprint as a characteristic distinguishing method combining similarity evaluation and quantification analysis, can be successfully used to assess the quality and to identify the authenticity of Rosa rugosa.

The River Habitat Survey (RHS) is a method for assessing the conditions of a river channel and valley, taking into account hydromorphological factors, and assessing the degree of naturalness or the degree of anthropogenic alteration within the channel and valley based on physical and landscape data. The hypothesis tested in this study was that the quality of river habitats demonstrated using the RHS should translate into the composition of their fauna. We investigated aquatic bugs (Heteroptera Aquatica), which are a group with considerable dispersal abilities and, at the same time, composed of stenotopic species associated with a particular environment as well as of eurytopic elements inhabiting a wide range of environments (REF). The research was carried out in a small lowland river, the River Krąpiel (north-western Poland) at 6 sites with 43 sub-sites included. Our analyses suggest the RHS method can predict the composition and quality of the aquatic bug fauna inhabiting a given river. Indicators of river habitat quality (HQA and RHQ) will be associated with different habitat types depending on the geographic location and type of river, once indicating habitats associated with the mainstream river and mineral substrate (mountain and small lowland rivers) and at other times habitats covered by vegetation with relatively slow water flow (large and medium lowland rivers). Therefore, RHS may be a good method for estimating the water bug fauna, linking it to the size and character of the river.

Within the field of nanomedicine, which is revolutionizing cancer treatment, solid lipid nanoparticles (SLNs) have shown advantages over conventional chemotherapy when tested on cancer cells in preclinical studies. SLNs have proven to be an innovative strategy for the treatment of tri-ple-negative breast cancer cells, providing greater efficiency than existing treatments in various studies. The encapsulation of antineoplastic drugs in SLNs has facilitated a sustained, controlled, and targeted release, which enhances therapeutic efficiency and reduces adverse effects. Moreover, the surface of SLNs can be modified to increase efficiency. For instance, the coating of these particles with polyethylene glycol (PEG) decreases their opsonization, resulting in a longer life in the circulatory system. The creation of positively charged cationic SLNs (cSLNs), achieved by the utilization of surfactants or ionic lipids with positively charged structural groups, increases their affinity for cell membranes and plasma proteins. Hyaluronic acid has been added to SLNs, so that the distinct pH of tumor cells, would stimulate the release of the drug and/or genetic materi-al. The current revision summarizes the recent research on SLNs, focusing on the encapsulation and transport of therapeutic agents with a cytotoxic effect on triple-negative breast cancer.

Colorectal cancer (CRC), found in the intestinal tract, is initiated, and progresses through various mechanisms, including dysregulation of signalling pathways. Several signalling pathways, such as EGFR and MAPK, involved in cell proliferation, migration, and apoptosis, are often dysregulated in CRC. Although cannabidiol (CBD) has previously induced apoptosis and cell cycle arrest in vitro in CRC cell lines, its effects on signalling pathways have not yet been determined. An in silico analysis was used here to assess partner proteins that can bind to CBD and docking simulations were used to predict precisely where CBD would bind to these selected proteins. A survey of current literature was used to hypothesize the effect of CBD binding on such proteins. The results predict that CBD could interact with EGFR, RAS/RAF isoforms, MEK1/2, and ERK1/2. The predicted CBD-induced inhibition might be due to CBD binding to the ATP binding site of the target proteins. This prevents the required phosphoryl transfer to activate substrate proteins and/or CBD binding to the DFG motif, thus reducing catalytic activity.

Background: Co-treatment of the fetal estrogen estetrol (E4) with androgen deprivation therapy (ADT) for advanced prostate cancer (PCa) may further inhibit endocrine PCa tumor stimulators including testosterone (T), prostate-specific antigen (PSA), follicle-stimulating hormone (FSH), and insulin-like growth factor-1 (IGF-1). Methods: A Phase II, double-blind, randomized, placebo-controlled study in advanced PCa patients requiring ADT (the PCombi study) was conducted to assess the effect of E4 co-treatment with LHRH agonist ADT on total T, free T, PSA, FSH, and IGF-1. Patients starting ADT were randomized 2:1 to 40 mg E4 (n=41) or placebo (n=21) for 24 weeks. Analyses were performed on the per-protocol population (PP), using the Wilcoxon-rank sum and the Kruskal-Wallis test. Results: The PP population consisted of 57 patients (37 ADT+E4; 20 ADT+placebo). All individual data of the four endocrine tumor stimulators are presented in figures in the paper and in supplementary tables, showing that E4 co-treatment almost completely suppressed FSH levels in all patients, on average by 98% versus 37% in the placebo group (p

Abstract: Background: In 2021, two randomized controlled trials (RCTs), TheraP and VISION, demonstrated that 177Lu-PSMA-617 as monotherapy was more effective for enhancing the decline of PSA than the comparator third-line treatments. Methods: Our review summarizes new RCTs that add to the use of radioligand therapy (RLT) for patients with high-risk prostate cancer (PCa). Results: Five past and present RCTs include 1139 patients. A RCT, ENZA-p, studied first-line treatment of patients with metastatic castration-resistant PCa (mCRPC). A combination of enzalutamide (ENZA) and 177Lu-PSMA-617 gave longer progression-free survival than ENZA as monotherapy. Other RCTs of patients with mCRPC, including the PSMAfore, and SPLASH trials, showed 177Lu-PSMA-617 as second-line treatment gave better progression-free survival than androgen receptor pathway inhibitors (combined p value 6 x 10-8). Conclusion: Patients with PCa may gain if they are given PSMA-RLT early in the treatment of PCa and as part of combination therapies.

Curcumin has attracted attention for its nontoxic chemopreventive effects; however, the specific pathways underlying its anticancer effects in colon cancer remain unclear. This study investigated the potential interplay between curcumin and integrin β1 in colon cancer. HCT116 and fibroblast cells were treated with curcumin, and cell proliferation was assessed using MTT assay and western blotting. We analyzed integrin β1 expression after curcumin treatment of HCT116 cells using western blotting and confocal microscopy. The roles of talin and rab25 in integrin β1 activation by curcumin were investigated using the same methods. Curcumin treatment significantly decreased the survival of HCT 116 cells but did not significantly affect the survival of fibroblast cells. Moreover, curcumin significantly increased integrin β1 expression in HCT 116 cells, which was primarily mediated by talin. In contrast, rab25 expression remained unchanged after curcumin treatment. Using rab25-specific siRNA knockdown experiments, we confirmed that curcumin increased integrin β1 expression even in the absence of rab25. Confocal microscopy revealed a dose-dependent increase in integrin β1 and talin expression, with consistent spatial distribution patterns in response to curcumin. This study highlights the clinical significance of curcumin as a selective anticancer agent in colon cancer by modulating integrin β1 expression through a talin-mediated pathway rather than through rab25.

Multiple myeloma (MM) is a common type of cancer that unfortunately leads to a significant number of deaths each year. The majority of the reported MM cases are detected in the advanced stages, posing significant challenges for treatment. Additionally, all MM patients eventually develop resistance or experience relapse, therefore advances in treatment are needed. However, developing new anti-cancer drugs, especially for MM, requires significant financial investment and a lengthy development process. The study of drug repurposing involves exploring the potential of existing drugs for new therapeutic uses. This can significantly reduce both time and costs, which is typically a major concern for MM patients. The utilization of pre-existing non-cancer drugs for various myeloma treatments presents a highly efficient and cost-effective strategy, considering their prior preclinical and clinical development. The drugs have shown promising potential in targeting key pathways associated with MM progression and resistance. Thalidomide exemplifies the success that can be achieved through this strategy. This review delves into the current trends, the challenges faced by conventional therapies for MM, and the importance of repurposing drugs for MM. This review highlights a noncomprehensive list of conventional therapies that have potentially significant anti-myeloma properties and anti-neoplastic effects. Additionally, we offer valuable insights into the resources that can help streamline and accelerate drug repurposing efforts in the field of MM.

Members of the SOX (SRY-related HMG-box) family of transcription factors are crucial for embryonic development and cell fate determination. This review investigates the role of SOX3 in cancer, as aberrations in SOX3 expression have been implicated in several cancers, including osteosarcoma, breast, esophageal, endometrial, ovarian, gastric, hepatocellular carcinomas, glioblastoma, and leukemia. These dysregulations modulate key cancer outcomes such as apoptosis, epithelial-mesenchymal transition (EMT), invasion, migration, cell cycle, and proliferation, contributing to cancer development. SOX3 exhibits varied expression patterns correlated with clinicopathological parameters in diverse tumor types. This review aims to elucidate the nuanced role of SOX3 in tumorigenesis, correlating its expression with clinical and pathological characteristics in cancer patients and cellular models. By providing a comprehensive exploration of SOX3 involvement in cancer, this review underscores the multifaceted role of SOX3 across distinct tumor types. The complexity uncovered in SOX3 function emphasizes the need for further research to unravel its full potential in cancer therapeutics.

The classification of tumors in subtypes, characterized by phenotypes determined by specific differentiation pathways, aids diagnosis and directs therapy towards targeted approaches. However, with the advent and explosion of next-generation sequencing, cancer phenotypes are turning out to be far more heterogenous than initially thought, and the classification is continually being updated to include more subtypes. Tumors are indeed highly dynamic and they can evolve and undergo various changes in their characteristics during disease progression. The picture becomes even more complex when tumor responds to a therapy. In all these cases, cancer cells acquire the ability to trans-differentiate, changing subtype, and adapt to changing microenvironments. These modifications affect the tumor's growth rate, invasiveness, response to treatment, and overall clinical behavior. Studying tumor subtype transitions is crucial for understanding tumor evolution, predicting disease outcomes, and developing personalized treatment strategies. We discuss this emerging hallmark of cancer and the molecular mechanisms involved at the crossroads between tumor cells and their microenvironment, focusing on four different human cancers in which tissue plasticity causes a subtype switch: breast cancer, prostate cancer, glioblastoma and pancreatic adenocarcinoma.

Amidst the burgeoning global concerns surrounding skin cancer, the quest for precise and efficient diagnostic methodologies has intensified. Conventional diagnostic approaches relying on subjective visual inspection by dermatologists often grapple with subjectivity and resource constraints. This predicament underscores the critical role of Artificial Intelligence (AI) in revolutionizing diagnostic paradigms by significantly enhancing accuracy and accessibility. This study embarks on an extensive exploration of skin cancer classification, specifically targeting the intricate task of 8-class skin cancer classification. Employing cutting-edge deep learning models on the ISIC2019 dataset, a comprehensive analysis was conducted utilizing a diverse array of pre-trained ImageNet architectures and Vision Transformer models. To counteract the inherent class imbalance in skin cancer datasets, a pioneering "Naturalize" augmentation technique was introduced, leading to the creation of indispensable tools—the Naturalized 2.4K ISIC2019 and groundbreaking Naturalized 7.2K ISIC2019 datasets—catalyzing advancements in classification accuracy. The pivotal role of AI in mitigating the risks of misdiagnosis and under-diagnosis in skin cancer becomes evident through this research. AI’s proficiency in analyzing vast datasets and discerning subtle patterns augments the diagnostic prowess of dermatologists significantly. Integration of AI-powered systems in skin cancer diagnosis holds immense promise in facilitating early detection and substantially improving patient outcomes. The meticulous evaluation employed quantitative measures such as confusion matrices, classification reports, and visual analyses using Score-CAM across diverse dataset variations. Astonishingly, the culmination of these endeavors culminated in an unprecedented achievement—100% average accuracy, precision, recall, and F1-Score—within the groundbreaking Naturalized 7.2K ISIC2019 dataset. This remarkable feat underscores the transformative potential of AI-driven methodologies, exemplifying their prowess in redefining the landscape of skin cancer diagnosis and management. In summary, this research represents a pivotal stride towards redefining dermatological diagnosis, showcasing the remarkable impact of AI-powered solutions in surmounting the challenges inherent in skin cancer diagnosis. The attainment of 100% across crucial metrics within the Naturalized 7.2K ISIC2019 dataset serves as a testament to the transformative capabilities of AI-driven approaches in reshaping the trajectory of skin cancer diagnosis and patient care.

Background: The association of age at onset of CRC and prevalence of KRAS G12C mutation is unclear; Methods: Retrospective multicenter study evaluating metastatic CRC patients from January 2019 to July 2023 treated at Oncoclinicas units, tested for tissue-based KRAS/NRAS and BRAF mutations in a centralized genomics lab. Mismatch repair (MMR) status was retrieved from different labs and electronic medical records, as were patient demographics (age, gender) and tumor sidedness. Chi-square test was used to examine the association between clinical and molecular variables, with p value <0.05 being statistically significant; Results: A total of 858 cases were included. The median age was 63.7 years (range 22-95) and 17.4% were less than 50 years old at diagnosis of metastatic CRC. Male patients represented 50.3% of the population. Sidedness distribution was left-side 59.2%, right-side 36.8% and not specified 4%. Prevalence of KRAS mutation was 49.4% and NRAS mutation 3.9%. Among KRAS mutated tumors, the most common variants were G12V (27.6%) and G12D (23.5%), while KRAS G12C was less frequent (6.4%), which represented 3.1% of the overall population. BRAF mutant cases were 7.3%, most commonly V600E. Only 5 (<1%) non-V600E mutations were detected. MSI-high or dMMR was present in 14 cases (1.6%). In the age-stratified analysis, left-sidedness (p<0.001) and KRAS G12C mutation (p=0.046) were associated with younger age (<50 years). In the sidedness-stratified analysis, BRAF mutation (p=0.001) and MSI-high/dMMR status (p=0.009), were more common in right-sided tumors; Conclusions: Our data suggest that KRAS G12C mutations are more frequent in early-onset metastatic CRC. To the best of our knowledge, this is the largest cohort in the Latin American population with mCRC reporting RAS, BRAF and MSI/dMMR status.

Tumor biomarkers have great potential in screening and their role could extend further from general population risk assessment to treatment response estimation and recurrence monitoring. Different molecular and cellular elements in blood, which give information about the status of an individual, make it a perfect compartment to develop noninvasive diagnostics approaches for cancer. The present study aimed to screen the most frequent tumor markers in the Angolan population according to age and gender. A whole blood sample was collected for each patient. Serum levels were measured using the electrochemiluminescence method, using the automated Cobas e411 equipment (Roche®) according to the manufacturer's instructions. The results of our study elucidated the relevance of tumor biomarkers in screening for different types of cancer. These results also highlight the robustness of the mean in suspected cases, which is 15 to 17 times higher in some markers than in non-suspected cases. More research is needed to elucidate the relevance of these biomarkers in the Angolan population.

Protein-drug interactions are crucial for understanding drug delivery and cell functions. Jacalin is a suitable molecule for such targeting, as it specifically recognizes the tu-mor-associated Thomsen-Friedenreich antigen that is expressed on the glycosylated proteins in cancer cells. The present paper describes the interaction of curcumin and jacalin, a possible carrier molecule for the delivery of antitumor drugs due to its ability to recognize tumor cells. Our results have shown that both steady state fluorescence and fluorescent label-ling of jacalin are two reliable methods to determine jacalin-curcumin interactions. The affinity of jacalin for curcumin is consistently within the micromolar range (using flu-orescence and microscale thermophoresis) showing high-affinity binding of the com-plex. In vitro experiments on the triple negative breast cancer MDA-MB-231 cells indi-cated inhibition of cell growth after treating with the jacalin-curcumin complex for 48 h. The cell survival fraction was significantly reduced to 50% after combined treatment. In this paper, we report for the first time about the jacalin-curcumin interaction. We quantified this unique biomolecular interaction and gathered additional information on the binding event. We observed that the jacalin-curcumin complex inhibits the proliferation of the triple negative breast cancer MDA-MB-231 cells.

Dietary supplements are widely embraced by cancer patients seeking complementary and integrative approaches to their care. Unfortunately, many patients do not discuss supplement use with physicians, often due to perceptions of physician indifference or negativity toward supplements. This communication gap exposes patients to unreliable information sources and, potentially, unnecessary risk. As the healthcare landscape evolves, patients increasingly value physicians who recognize their pivotal role in shaping healthcare decisions. This patient-centered perspective emphasizes the provision of evidence-based information tailored to individual needs, open discussions on potential risks, and shared decision-making. It underscores the importance of respecting patient autonomy, offering alternative options, documenting preferences, and ensuring ongoing support while coordinating with the healthcare team. To address these needs, healthcare providers should transform their perspectives and become expert guides who embrace patients as informed, empowered participants. This approach prioritizes open dialogue that considers both facts and uncertainties regarding dietary supplement use, allowing for mutually informed decision-making. Here, we review the literature and present a practical approach emphasizing open discussions, transparency, and respect for patient autonomy. Following this approach, healthcare providers can empower patients to navigate the complexities of dietary supplement use in the context of cancer care, ultimately safeguarding patient safety and well-being.

This study aimed to identify microRNAs associated with histological grade using comprehensive microRNA analysis data obtained by next-generation sequencing in early-stage invasive breast cancer. RNA-seq data from normal breast and breast cancer samples were compared to identify candidate microRNAs with different expressions using bioinformatics. A total of 108 microRNAs were significantly differentially expressed between normal breast and breast cancer tissues. Using clinicopathological information and microRNA sequencing data of 430 patients with breast cancer from The Cancer Genome Atlas (TCGA), the differences in candidate microRNAs between low- and high-grade cases were compared. Comparing the expression of the 108 microRNAs between low- and high-grade cases, 25 and 18 microRNAs were significantly upregulated and downregulated, respectively, in high-grade cases. Clustering analysis of the TCGA cohort using these 43 microRNAs identified two groups strongly predictive of histological grade. miR-3677 is a microRNA upregulated in high-grade breast cancer. The outcome analysis revealed that patients with high miR-3677 expression had a significantly worse prognosis than those with low miR-3677 expression. This study showed that microRNAs were associated with histological grade in early-stage invasive breast cancer. These findings contribute to the elucidation of a new mechanism of breast cancer growth regulated by specific microRNAs.

(1) Background: Breast cancer (BC) is the second largest cause of mortality in female worldwide. Besides from basic risk factors, there are several hereditary variables that contribute to BC. Breast cancer has been linked to a variety of nuclear DNA changes as well as mitochondrial DNA alterations. The aim of this study was to analysis the association of mitochondrial tRNA leucine2 gene with BC. (2) Material and methods: In the current study, 24 samples have been collected from various families in Peshawar. DNA was extracted from Blood. PCR was used to amplify the mitochondrial tRNA MT-TL2 gene, and 22 samples were sequenced. The sequence was compared with accession #NC-012920.1 of the revised Cambridge Reference Sequence (rCRS). (3) Results: The results (Chromatograph, nucleotide sequence and rCRS alignment) shows mutations in mitochondrial tRNA MT-TL2 gene in our participants is not the cause of Breast cancer. (4) Conclusion: Yet, a significant number of BC patients must be studied, and their full mitochondrial DNA must be analyzed. This will provide an indication of the potential DNA marker that might be used to prevent BC deaths at the earliest stages.

Prostate cancer (PCa) is characterised by androgen-dependency. Unfortunately, under anti-androgen treatment pressure, castration-resistant prostate cancer (CRPC) emerges, characterised by heterogeneous cell populations that, over time, lead to the development of different androgen-dependent or -independent phenotypes. Despite important advances in therapeutic strategies, CRPC remains incurable. Context-specific essential genes represent valuable candidates for targeted anti-cancer therapies. Through the investigation of gene and protein annotations and the integration of several published transcriptomic data, we identified two consensus lists to stratify PCa patients' risk and discriminate CRPC phenotypes based on androgen receptor activity. ROC and Kaplan-Meier survival analyses were used for gene set validation in independent datasets. We further evaluated these genes for their association with cancer dependency. The deregulated expression of the PCa-related genes was associated with overall and disease-specific survival, metastasis and/or high recurrence risk, while the CRPC-related genes clearly discriminated between adeno and neuroendocrine phenotypes. Some of the genes showed context-specific essentiality. We further identified candidate drugs through a computational repositioning approach for targeting these genes and treating lethal variants of PCa. This work provides a proof-of-concept for the use of an integrative approach to identify candidate biomarkers involved in PCa progression and CRPC pathogenesis within the goal of precision medicine.

This narrative review aims to clarify the role of tertiary lymphoid structures in breast cancer. We examine their development, composition, prognostic value and current ways of recognising them. A comprehensive literature review was performed using PubMed/Medline, Scopus and EMBASE databases. A significant area of interest in breast cancer research involves targeting immune checkpoint molecules, particularly in the triple-negative subtype, where treatment options remain limited. However, existing biomarkers have limitations in accurately predicting treatment response.  In this context, tertiary lymphoid structures (TLS) emerge as a prognostic biomarker and also as a promising predictive marker for response. TLS are ectopic lymphoid formations or neo-organogenesis that can develop after prolonged exposure to inflammatory signals mediated by chemokines and cytokines. Their presence is inversely correlated with estrogen receptor (ER) and/or progesterone receptor (PR) expression, but positively associated with a higher pathologic complete response rate and improved overall  survival. In certain scenarios, TLS-positive tumors were associated with improved outcomes regardless of the presence of PDL-1 (programmed cell death ligand 1) expression or and TILs (tumor-infiltrating lymphocytes).

Abstract Background: Gastric cancer, particularly adenocarcinoma, is a significant global health concern. Environmental risk factors, such as Helicobacter pylori infection and diet, play a role in its development. Purpose: This study aimed to characterize the chemical composition and evaluate the in vitro antibacterial and antitumor activities of AOME. Additionally, morphological changes in gastric cancer cell lines were analyzed. Study design: AOME was analyzed using HPLC-MS/MS and its antibacterial activity against H. pylori was assessed using the broth microdilution method. MIC and MBC values were determined, and positive and negative controls were included in the evaluation. Methods: Anticancer effects were assessed through in vitro experiments using AGS, KATO-III, and SNU-1 cancer cell lines. The morphological changes were examined through SEM and TEM analyses. Results: AOME contained several compounds, including caffeic acid, rutin, and hyperoside. The extract displayed significant antimicrobial effects against H. pylori, with consistent MIC and MBC values of 3.70 ± 0.09 mg/mL. AOME reduced cell viability in all gastric cancer cell in a dose and time-dependent manner. Morphological analyses revealed significant ultrastructural changes in all tumor cells lines, suggesting the occurrence of cellular apoptosis. Conclusions: This study demonstrated that AOME possesses antimicrobial activity against H. pylori and potent antineoplastic properties in gastric cancer cell lines. AOME holds promise as a natural resource for innovative nutraceutical approaches in gastric cancer management. Further research and in vivo studies are warranted to validate its potential clinical applications.

The role of desmoglein-3 (DSG3) in oncogenesis is unclear. This study aimed to uncover molecular mechanisms through comparative transcriptome analysis in oral cancer cells, defining potential key genes and associated biological processes related to DSG3 expression. Four mRNA libraries of oral squamous carcinoma H413 cell lines were sequenced and 599 candidate genes exhibited differential expression between DSG3-overexpressing and matched control lines, with 12 genes highly significantly differentially expressed, including 9 upregulated and 3 downregulated. Genes with known implications in cancer, such as MMP-13, KRT84, OLFM4, GJA1, AMOT, and ADAMTS1, were strongly linked to DSG3 overexpression. Gene ontology analysis indicated that the DSG3-associated candidate gene products participated in crucial cellular processes such as junction assembly, focal adhesion, extracellular matrix formation, intermediate filament organization, and keratinocyte differentiation. Validation of RNA-Seq was performed through qRT-PCR, Western blotting, and immunofluorescence analyses. Furthermore, transmission electron microscopy meticulously examined desmosome morphology, revealing slightly immature desmosome structure in DSG3-overexpressing cells compared to controls. No changes in desmosome frequency and diameter were observed between the two conditions. This study underscores intricate and multifaceted alterations associated with DSG3 in oral squamous carcinoma cells, implying a potential oncogenic role of this gene in biological processes that enable cell communication, motility and survival.

Malignant neoplasms arising from the gastrointestinal (GI) tract are among the most common cancer types with a high mortality rate. Despite advances in treatment in a small subgroup harboring targetable mutations, the outcome remains poor, accounting for one in three cancer-related deaths observed globally. As a promising therapeutic option in various tumor types, immunotherapy with immune checkpoint inhibitors has also been evaluated in GI cancer, albeit with limited efficacy except for a small subgroup expressing microsatellite instability. In the quest for more effective treatment options, energetic efforts have been placed to evaluate the role of several immunotherapy approaches comprising of cancer vaccines, adoptive cell therapies and immune checkpoint inhibitors. In this review, we report our experience with personalized dendritic cell cancer vaccine and cytokine-induced killer cell therapy in three patients with GI cancers and summarize current clinical data on combined immunotherapy strategies.

A wide panel of microtubule-associated proteins and kinases is involved in coordinated regula-tion of the microtubule cytoskeleton and may thus represent valuable molecular markers contrib-uting to major cellular pathways deregulated in cancer. We previously identified a panel of 17 microtubule-related (MT-Rel) genes that are differentially expressed in breast tumors showing resistance to taxane-based chemotherapy. In the present study, we evaluated the expression, prognostic value and functional impact of these genes in breast cancer. We show that 14 MT-Rel genes (KIF4A, ASPM, KIF20A, KIF14, TPX2, KIF18B, KIFC1, AURKB, KIF2C, GTSE1, KIF15, KIF11, RACGAP1, STMN1) are up-regulated in breast tumors compared with adjacent normal tissue. Six of them (KIF4A, ASPM, KIF20A, KIF14, TPX2, KIF18B) are overexpressed by more than 10-fold in tumor samples and four of them (KIF11, AURKB, TPX2 and KIFC1) are essential for cell survival. Overexpression of all 14 genes, and underexpression of 3 other MT-Rel genes (MAST4, MAPT and MTUS1) are associated with poor breast cancer patient survival. A Systems Biology approach highlighted three major functional networks connecting the 17 MT-Rel genes and partners, which are centered on spindle assembly, chromosome segregation and cytokinesis. Together our studies identified mitotic Aurora kinases and their substrates as major targets for therapeutic approaches against breast cancer.

The role of upfront primary tumor resection (PTR) in patients with unresectable metastatic col-orectal cancer (CRC) without severe symptoms remains controversial. We retrospectively ana-lyzed the role of PTR in overall survival (OS) in different subgroups. Among 331 patients diag-nosed with synchronous metastatic CRC between 2010 and 2020, 223 were analyzed. The PTR group (n = 42) showed better performance (p = 0.038); higher frequencies of right-sided origin (p = 0.014), T4 stage (p = 0.005), M1a stage (p = 0.015), and <2 organ metastases (p = 0.002); and re-ceived fewer targeted agents (p < 0.001) than the chemotherapy group (n = 181). The PTR group showed longer OS (20.5 versus 14.0 months, p = 0.016), but PTR was marginally related to OS in multivariate analysis (p = 0.060). Male sex (p = 0.022), good performance status (p = 0.07), left-sided tumor (p = 0.069), low serum carcinoembryonic antigen level (p = 0.092), T3 stage (p = 0.029), M1a stage (p = 0.025), <2 organ metastases (p = 0.017), and administration of targeted agents, especially bevacizumab (p = 0.024), were related to survival benefit after PTR. Upfront PTR should be considered when selecting patients with favorable prognoses for bevacizumab administration.

Colorectal cancer is the third most common disease and the second most common cause of death in the world. The drug for second-line treatment depends on the drugs used in first-line treatment and biomarker status. As biomarkers, the RAS gene, BRAF gene, and dMMR/MSI-H, TMB-H, and HER2 statuses have been established in clinical practice, and the corresponding molecularly targeted therapeutic agents are selected based on biomarker status. Given the frequency of biomarkers, it is assumed that when patients move on to second-line treatment, an angiogenesis inhibitor is selected in many cases. For second-line treatment, three angiogenesis inhibitors, bevacizumab (BEV), ramucirumab (RAM), and aflibercept (AFL), are available, and one of them is combined with cytotoxic agents. These three angiogenesis inhibitors are known to inhibit angiogenesis through different mechanisms of action. Although no useful biomarkers are established for selecting angiogenesis inhibitors, previous biomarker studies have suggested that angiogenesis-related factors such as VEGF-A and VEGF-D might be predictors of therapeutic efficacy of angiogenesis inhibitors. These biomarkers are measured as protein levels in plasma and are considered to be hopeful biomarkers. We consider that the rationale for selecting among these three angiogenesis inhibitors should be clarified to benefit patients.

The main known function of Nudix hydrolase 2 (Nudt2) is to hydrolyze the secondary messenger diadenosine 5', 5’’’-p1, p4-tetraphosphate (Ap4A). In this study we examined the role of Nudt2 in breast carcinoma through its expression in the human invasion ductal carcinoma tissues, and its functions in human triple negative breast cancer (TNBC) cell lines. A significantly high expression of Nudt2 in the human invasion ductal carcinoma tissues was observed in our study. Knockdown of Nudt2 in TNBC cell lines showed a significant reduction in cellular proliferation via the Ki67 marker, accompanied by G0/G1 phase cell cycle arrest. A significant reduction in the migration and invasion of Nudt2 knockdown TNBC cell lines was also observed. The effect of Nudt2 knockdown in the TNBC cell lines on tumorigenicity and anchorage-independent growth was assessed, where significant reductions in the Nudt2 knockdown TNBC cell lines were found. It can therefore be concluded that Nudt2 plays a significant role in promoting TNBC growth.

Background: The incidence of prostate cancer (PC) has been risen annually. Despite the diagnosis is made mainly with non-metastatic PC, mortality is explained by the metastatic disease (mPC). Without a doubt there is an intermediate scenario in which patients have no mPC but will have initiated a metastatic cascade through an epithelial-mesenchymal transition. There is indeed a need for more and better tools to predict what patients will progress in the future to non-localized clinical disease or already have micrometastatic disease, and therefore, will clinically progress after primary treatment. Biomarkers for predicting mPC are still under development; there are few studies and not much evidence of their usefulness. Summary: This review is focused on tissue-based genomic biomarkers (TBGB) for predicting metastatic disease. We developed four main research questions that will attempt to answer according to the current evidence. Why is important to predict metastatic disease? Which tests are available to predict metastatic disease? What impact should there be on clinical guidelines and clinical practice in predicting metastatic disease? What are current prostate cancer treatments? Key Messages: Knowing useful predict tools could help determine which patients may need multimodal or adjuvant treatment even with a localized disease, and in consequence, what patients do not need more than a single modality of treatment. The importance of predicting metastasis is fundamental, given that once metastasis is diagnosed, the quality of life (QoL) and survival drop dramatically.

The noncoding RNAs (ncRNAs) are small transcript sequences that do not encode proteins but participate in the regulation of gene expression at the post-transcriptional level playing important biological roles such as proliferation and differentiation. In the tumor microenvironment, the dysregulated immunological response can participate in the progression and negative phenotype of cancer, the variability of switch cell differentiation and activation of the different immune cell lineages showed differential regulation by the type of cancer. Recent evidence showed that the upregulation of lncRNA can be used as a biomarker and predictive indicator for cancer progression. The use of lncRNA to turn off the tumor immune response and activate the anti-tumoral immune response is day by day a promising reality for the control of cancer. However, is imperatively elucidated the role of each ncRNA identified as well as its respective molecular pathways regulated, including the immune checkpoints, before its application at the clinical level. The correct delivery of lncRNA or mimics to inhibit its expression using the most efficient carriers to the cell or cellular organelle is a science that should continue to be developed.

Gastric cancer is among the top 5 causes of cancer-related death worldwide. Preoperative chemotherapy has been established as an option in patients with locally advanced gastric cancer. However, chemotherapy yields variable results, owing to the cellular and molecular heterogeneity of this disease. Identifying patients who did or did not respond to preoperative therapy can allow clinicians to alter treatment modalities and provide important information related to prognostication. Pathologic response to preoperative therapies, called Tumor Response Grade (TRG), has been evaluated to quantify treatment response. Multiple systems for TRG have been established. However, literature has demonstrated inconsistent results for TGR systems and prognosis, possibly due to variability in interpretation of tumor response between systems and interobserver variability. Radiographic response to preoperative therapies using RECIST 1.1 criteria and endoscopically-assessed tumor response have demonstrated association with survival; however their use in gastric cancer remains challenging given the inability to accurately and consistently identify and measure the tumor, especially in the setting of neoadjuvant therapy where treatment-related changes can obscure the gastric wall layers. This review is focused on summarizing the available literature related to evaluating TRG in gastric cancer, as well as providing a brief overview on the use of radiographic and endoscopic methods to assess response to preoperative therapies. Lastly, we outline future directions regarding the use of a universal TRG system to guide care and assist with prognosis.

Unlike plants which have special gravity-sensing cells, such special cells in animals are yet to be discovered. However, microgravity, the condition of apparent weightlessness, causes bone, muscular and immune system dysfunctions in astronauts following spaceflights. Decades of investigations show correlations between these organ and system-level dysfunctions with changes induced at the cellular level both by simulated microgravity as well as microgravity conditions in outer space. Changes in single bone, muscle and immune cells include morphological abnormalities, altered gene expression, protein expression, metabolic pathways and signaling pathways. These suggest that human cells mount some response to microgravity. However, the implications of such adjustments on many cellular functions and responses are not clear. Here, we addressed the question whether microgravity induces alterations to drug response in cancer cells. We used both adherent cancer cells (T98G) and cancer cells in suspension (K562) to confirm known effects of microgravity and then treated the K562 cells with common cancer drugs (hydroxyurea and paclitaxel) following 48 hours of exposure to microgravity via a NASA-developed rotary cell culture system. Fluorescence-guided morphometry revealed microgravity-induced loss of the significant reduction (p &lt; 0.0l) to the nuclear to cytoplasm ratio of cancer cells treated with hydroxyurea. Our results call for more studies on impact of microgravity on cellular drug-response, in view of the growing need for space medicine, as space exploration grows.

Background and Objectives: Gastric cancer (GC) is one of the most commonly diagnosed cancer and the fourth cause of cancer death worldwide. Personalised treatment improves GC outcomes. A molecular classification is needed to choose the appropriate therapy. A classification that uses on-slide biomarkers and formalin-fixed and paraffin-embedded (FFPE) tissue is preferable to comprehensive genomic analysis. In 2016, Setia et al. proposed an on-slide classification, however this is not in widespread use. We propose a modification of this classification that has six subgroups: GC associated with Epstein-Barr virus (GC EBV+), GC with mismatch repair deficiency (GC dMMR), GC with epithelial-mesenchymal transformation (GC EMT), GC with functional loss of p53 due to mutation (GC p53m), CG with intact p53 (GC p53wt) and GC not otherwise specified (GC NOS). This classification also has provision for biomarkers for current or emerging targeted therapies (Her2, PD-L1 and Claudin18.2). Here we assess the implementation and feasibility of this inclusive working classification. Materials and Methods: We constructed a tissue microarray library from a cohort of 79 resection cases from FFPE tissue archives. We used a restricted panel of on-slide markers (EBER, MMR, E-cadherin, beta-catenin and p53), defined their interpretation algorithms, and assigned each case to a specific molecular subtype. Results: GC EBV(+) cases were 6%, GC dMMR cases were 20%, GC EMT cases were 14%, GC p53m cases were 23%, GC p53wt cases were 29% and GC NOS cases were 8%. Conclusions: This working classification uses markers that are widely available in Histopathology and are easy to interpret. A diagnostic subgroup is obtained for 92% of the cases. The proportion of cases in each subgroup is in keeping with other published series. Widescale implementation appears feasible. A study using endoscopic biopsies is warranted.

The prompt and accurate diagnosis of breast lesions, including the distinction between cancer, non-cancer, and suspicious cancer, plays a crucial role in the prognosis of breast cancer. In this paper, we introduce a novel method based on feature extraction and reduction for detection of breast cancer in mammography images. First, we extract features from multiple pre-trained convolutional neural network (CNN) models, and then concatenate them. The most informative features are selected based on their mutual information with the target variable. Subsequently, the selected features can be classified using a machine learning algorithm. We evaluate our approach using four different machine learning algorithms, and our results demonstrate that the neural network-based classifier yields an accuracy as high as 92% for the RSNA dataset which is a new dataset that provides two views and additional features such as age. We compare our proposed algorithm with state-of-the-art methods and demonstrate its superiority, particularly in terms of accuracy and sensitivity. For the MIAS dataset, we achieve an accuracy as high as 94.5%, and for the DDSM dataset, an accuracy of 96% is attained. These results highlight the effectiveness of our method in accurately diagnosing breast lesions and surpassing existing approaches.

The methyltransferase, KMT5A has been proposed as an oncogene in prostate cancer and therefore represents a putative therapeutic target. To confirm this hypothesis we have performed a microarray study in a prostate cancer cell line model of androgen independence following KMT5A knockdown in the presence of transcriptionally active androgen receptor (AR) to understand which genes and cellular processes are regulated by KMT5A in the presence of an active AR. We observed that 301 genes were down-regulated whilst 408 were up-regulated when KMT5A expression was reduced. KEGG pathway and Gene Ontology analysis revealed apoptosis and DNA damage signaling are up-regulated in response to KMT5A knockdown whilst protein folding and RNA splicing were down-regulated. Under these conditions, the top non-AR regulated gene was found to be CDC20, a key regulator of the spindle assembly checkpoint with an oncogenic role in several cancer types. Further investigation revealed that KMT5A regulates CDC20 in a methyltransferase dependent manner to modulate both histone H4K20 methylation within its promoter region and indirectly via the p53 signalling pathway. A positive correlation between KMT5A and CDC20 expression was also observed in clinical prostate cancer samples further supporting this association. Therefore, we conclude that KMT5A is a valid therapeutic target for the treatment of prostate cancer and CDC20 could potentially be utilized as a biomarker for effective therapeutic targeting.

Vessel co-option correlates with resistance against anti-angiogenic agents and chemotherapy in colorectal cancer liver metastasis (CRCLM). We previously identified higher intensity of neutrophils in the tumour microenvironment of vessel co-opting CRCLM lesions compared to their angiogenic counterparts. Herein, we demonstrated that over 50% of the neutrophils in vessel co-opting lesions are expressing pro-apoptotic markers including cleaved caspase-3 and poly (ADP-ribose) polymerase-1 (PARP-1). Our previous publications suggested upregulation of transforming growth factor-beta (TGFβ1) in the microenvironment of vessel co-option CRCLM. Therefore, we examined the effect of TGFβ1 on the expression of cleaved caspase-3 and PARP-1 in neutrophils in vitro. Significantly, we noticed the upregulation of pro-apoptotic markers upon exposure to TGFβ1. This finding might pave the way to determine the role of neutrophils in developing vessel co-option in CRCLM in the future.

We attempted to understand the cervical cancer patient samples through Whole Exome Sequencing. We derived the variants from raw reads via our in-house benchmarked pipeline and validated the variants by IGV. This is the first cervical cancer exome data from the Indian cohort. Background: Cervical cancer (CC) is caused mainly by persistent infections of high-risk HPV, reduced parity, and factors like a decrease in average socioeconomic levels. We keep this because no cervical cancer exome data is available from the Indian cohort. Methods: The CC patient clinical samples were initially subjected to preparation using Qiagen DNA extraction, quantified, and the library preparation using the Agilent target enrichment system. Further, exome capture by Illumina platform (100X), quality check, alignment, and variant calling followed by the downstream analysis and finally visualized by IGV. Results: We observed a large number of SNVs or mutations from an Indian perspective, such as KMT2C, OR4M1, PDPR2P, EPHB1, FAS, OPCML, MGST1, C1QTNF9, HS6ST3, OR4K2, PRPSAP2, KCNJ12, FIGNL1, SFXN1, BAGE2, ARVCF, NAMPT variants of significance, unknown significance and possibly significant are reported. Conclusion: For the first time, KMT2C is observed as a novel potent mutation and pathogenic, showing the variant position at (7:152265091, T>A, SNV 62478356) from the Indian context in CC. Further, we visualized and validated the mutations using the Integrative Genomic Viewer (IGV) browser. Finally, we discuss the inherent challenges through KMT2C mutations.

Multiple biological pathways manifest and latent, meant for human survival, become a liability in cancer cure. With an increasing understanding of innumerable complex paths, cancer progression and development of resistance is no surprise. For the three “vasculature-immune-phenotypic” fundamental changes, hypoxia is the maestro orchestrating the whole gamut of changes (through the master manipulator - HIF-1 α), simultaneously transactivating hundreds of pro-angiogenic genes. Such a complex molecular bio-network begs the question, “Is our cancer research caught in such a tangled web that we have lost sight of the Spider?”. Hypoxia is this Spider weaving compensatory webs with every intervention/ obstruction. Anti-angiogenic (AAG) research has been conducted mainly in silos – exploring independent paths. This review conceptualizes a convergence of a multitude of research worldwide to a single theme of normalizing vasculature as a primary baseline for overcoming resistance to AAGs or their combinations.

The purpose of this review is to present the current knowledge about the diagnostic and treatment options in bladder cancer (BCa) patients with clinically positive lymph nodes (cN+). In this review compaction of CT and MRI performance in preoperative prediction of lymph node invasion (LNI) in BCa patients was presented, along with other diagnostic methods. Most scientific societies do not distinguish cN+ patients in their guidelines, recommendations concern muscle-invasive bladder cancer (MIBC) and differ between associations. Currently, the standard treatment of patients with MIBC is radical cystectomy (RC) with bilateral pelvic lymph node dis-section (PLND). The template of PLND and its therapeutic value remain debatable. Moreover, most guidelines recommend neoadjuvant chemotherapy (NAC). However, there is still lack of definitive evidence of the superiority of neoadjuvant chemotherapy over adjuvant chemotherapy. Nevertheless, the curative treatment that provides the best long-term survival in cN+ patients is a multimodal approach with a combination of chemotherapy and RC. Recent studies demonstrate the growing importance of immunotherapy. Special attention should be paid to cN+ BCa patients as the oncological outcomes are significantly worse for this group.

The recent approval of 177Lu PSMA-617 (Pluvicto®) by the United States Food and Drug Administration (FDA) is the culmination of decades of work in advancing the field of targeted radionuclide therapy for metastatic prostate cancer. 177Lu PSMA-617, along with the bone specific radiotherapeutic agent, 223RaCl2, are now commonly used in routine clinical care as a tertiary line of therapy for men with metastatic castrate resistant prostate cancer and for osseus metastatic disease respectively. While these radiopharmaceuticals are changing how metastatic prostate cancer is classified and treated, there is relatively little guidance to the practitioner and patient as to how best utilize these therapies, especially in conjunction with other more well-established regimens including hormonal, immunologic, and chemotherapeutic agents. This review article will go into detail about the mechanism and effectiveness of these radiopharmaceuticals and less well known classes of targeted radionuclide radiopharmaceuticals including alpha emitting prostate specific membrane antigen (PSMA) -, gastrin-releasing peptide receptor (GRPR) -, and somatostatin targeted radionuclide therapeutics. Additionally, a thorough discussion of the clinical approach of these agents is included and required futures studies.

We previously described a model of deep intrinsic resistance of breast cancer wherein we used a function-based approach to selection of cancer cells that can survive a variety of challenges in prolonged but reversible quiescence. Our experimental results suggested that resistant cancer cells possess a variety of mechanisms, including modifications of the epigenome and transcriptome, for generating a high degree of cellular heterogeneity. In the present study, we evaluated JIB-04, a small-molecule epigenetic inhibitor initially discovered to inhibit cancer growth, to determine its ability to affect deep intrinsic resistance in our breast cancer model. We found that long pretreatment with JIB-04 sensitized resistant triple-negative inflammatory breast cancer cells and their parental cell line SUM149 to the chemotherapeutic drugs doxorubicin and paclitaxel. Resistant cancer cells derived from another inflammatory breast cancer cell line, FC-IBC02, were considerably more sensitive to JIB-04 than was the parental cell line. Investigating a mechanism of sensitization, we found that JIB-04 exposure increased the expression of PD-L1 in resistant cells, suggesting that JIB-04 may also sensitize resistant breast cancer cells to anti-PD-L1 immune therapy. Finally, these results support the usefulness of our experimental strategy for evaluating anticancer agents such as JIB-04 that may halt cancer evolution and prevent development of cancer resistance to currently used therapies.

The purpose of this review is to present the current role of ultrasound-based techniques in the diagnostic pathway of prostate cancer (PCa). With overdiagnosis and overtreatment of a clinically insignificant PCa over the past years, multiparametric magnetic resonance imaging (mpMRI) became recommended for every patient suspected of PCa before performing a biopsy. It enabled targeted sampling of the suspicious prostate regions, improving the accuracy of the traditional systematic biopsy. However, mpMRI is associated with high costs, relatively low availability, long and separate procedure or exposure to the contrast agent. The novel ultrasound modalities such as shear wave elastography (SWE), contrast-enhanced ultrasound (CEUS) or high frequency micro-ultrasound (MicroUS) may be capable of maintaining the performance of mpMRI without its limitations. Moreover, the real-time lesion visualization during biopsy would significantly simplify the diagnostic process. Another value of these new techniques is the ability to enhance the performance of mpMRI by creating the image fusion of multiple modalities. Such models might be further analyzed by artificial intelligence to mark the regions of interest for investigators and help to decide about the biopsy indications. The dynamic development and promising results of new ultrasound-based techniques should encourage researchers to thoroughly study their utilization in prostate imaging.

In the era of nanotechnology, researchers are implementing point to care service to cancer patients to detect malignancy beforehand and to reduce the mortality rate of cancers. Cancer is known to be the most fatal disease among all other diseases and the survivability from cancer is quite impossible if the stage of the cancer is an advanced level. Though the early detection of cancer can increase the chances of survival with a double fold. Biosensor is a part of nanotechnology which is capable to provide point to care service in the field of medicine. With the rising number of cancer occurrences being identified around the world and the increasing number of deaths because of the identification of advanced cancer, biosensors can play a significant part in the early detection of cancer. New molecular methods, including as genomic and proteomic approaches, are increasingly being used to study patient molecular profiles. When such diagnosis method is paired with bioinformatics tools, they generate new data that can be used to discover new disease biomarkers. Finding precise and sensitive indicators that are corelated to a specific disease, as with many other diseases, can be challenging. Furthermore, the concentration of biomarkers in biological fluids varies according to illness states and phases. Peptides, proteins, up or down regulated expression of gene markers, and gene alternation are all examples of molecular markers that are commonly used to diagnose cancer. In this article, we have highlighted six different deadliest cancers such as Ovarian, Breast, Prostrate, Lung, Colorectal and Liver cancer. The article contains distinct types of biomarkers which are normally found in these kinds of cancer and generally used as a potential diagnostic target in the medicine field. The article mainly summarized the application of different types of biosensors devices in the detection of the mostly found biomarkers in the above cancer types.

Liquid biopsy via isolation of circulating tumour cells (CTCs) represents a promising diagnostic tool capable of supplementing state-of-the-art for prostate cancer (PC) prognosis. Unfortunately, most of CTC technologies, such as AdnaTest or Cellsearch, critically rely on the Epithelial-Cell-Adhesion-Molecule (EpCAM) marker, limiting the possibility of detecting stem-like cells (CSCs) and mesenchymal-like cells (EMT-CTCs) that are present during PC progression. In this tontext, dielectrophoresis (DEP) is an epCAM independent, label-free, enrichment system, separating rare cells simply on the basis of their specific electrical properties. As compared to other technollgies, DEP represents a superior technique in terms of running costs, cells yield and specificity, but due to its higher complexity, requires still further technical as well as clinical development. Interestingly, DEP can be improved by the use of microfluid, nanostructured materials and fluoroimaging in order to increase its potential applications. In the context of PC, the utility of DEP can be translated in its capacity to detect CTC in the bloodstream in their epithelial, mesenchymal, or epithelial-mesenchymal phenotypes, which should be taken into account when choosing CTC enrichment and analysis methods for PC prognosis and early diagnosis.

One of the most dangerous diseases that threaten people is Cancer. Cancer if diagnosed in earlier stages can be eradicated with its life threatening consequences. In addition, accuracy in prediction plays a major role. Hence, developing a reliable model that contributes much towards the medical community in early diagnosis of Biopsy images with perfect accuracy come to the scenario. The article aims towards development of better predictive models using multi-variate data and high-resolution diagnostic tools in clinical cancer research. This paper proposes the social spider optimization (SSO) algorithm tuned neural network to classify microscopic biopsy images of cancer. The significance of the proposed model relies on the effective tuning of the weights of the NN classifier by the SSO algorithm. The performance of the proposed strategy is analysed with the performance metrics, such as accuracy, sensitivity, specificity, and MCC measures, and are attained to be 95.9181%, 94.2515%, 97.125%, and 97.68% respectively, which shows the effectiveness of the proposed method in effective cancer disease diagnosis.

Background: Zebrafish (Danio rerio) is a model organism emerged for the study of human cancer. Compared with the murine model, the zebrafish model has several properties ideal for personalized therapies. The transparency of the zebrafish embryos and the development of the pigment-deficient “casper” zebrafish line give the capacity to directly observe cancer formation and progression in the living animal. Automatic quantification of cellular proliferation in vivo is critical to the development of personalized medicine. Methods: A new methodology was defined to automatically quantify the cancer cellular evolution. ZFTool was developed to establish a base threshold that eliminates the embryo auto-fluorescence and automatically measures the area and intensity of GFP (green-fluorescent protein) marked cells and define a proliferation index. Results: Proliferation index automatically computed on different targets demonstrates the efficiency of ZFTool to provide a good automatic quantification of cancer cell evolution and dissemination. Conclusion: Our results demonstrate that ZFTool is a reliable tool for the automatic quantification of the proliferation index, being a measure of cancer mass evolution in zebrafish eliminating the influence of its autofluorescence.

The Herpes Virus Entry Mediator (HVEM) delivers a negative signal to T cells mainly through the B and T Lymphocyte Attenuator (BTLA) molecule and thus, could represent a novel immune checkpoint during an anti-tumor immune response. A formal demonstration that HVEM can be targeted for cancer immunotherapy is however still lacking. Here, we first show that HVEM and BTLA were associated to a worse prognosis in patients with prostate adenocarcinomas, indicating a detrimental role for this pair of molecule during prostate cancer progression. We then show that a monoclonal antibody to human HVEM significantly impacted the growth of a prostate cancer cell line in immuno-compromised NOD.SCID.gc-null mice reconstituted with human T cells. Using CRISPR/Cas9, we showed that HVEM expression by the tumor was mandatory to observe the therapeutic effect. Mechanistically, tumor control was dependent on CD8+ T cells and was associated to an increase in the proliferation and number of tumor-infiltrating leukocytes. Accordingly, the expression of genes belonging to various T cell activation pathways were enriched in tumor infiltrating leukocytes, whereas genes associated with immuno-suppressive pathways were decreased, possibly resulting in modifications of leukocyte adhesion and motility. Finally, we developed a simple in vivo assay in humanized mice to directly demonstrate that HVEM was an immune checkpoint for T-cell mediated tumor control. Our results show that targeting HVEM is a promising strategy for prostate cancer immunotherapy.

The secretory pathway Ca2+-ATPase SPCA2 is a tumor suppressor in triple receptor negative breast cancer (TNBC), a highly aggressive molecular subtype that lacks tailored treatment options. Low expression of SPCA2 in TNBC confers poor survival prognosis in patients. Previous work has established that re-introducing SPCA2 to TNBC cells restores basal Ca2+ signaling, represses mesenchymal gene expression, mitigates tumor migration in vitro and metastasis in vivo. In this study, we examined the effect of histone deacetylase inhibitors (HDACi) in TNBC cell lines. We show that the pan-HDACi vorinostat and the class I HDACi romidepsin induce dose-dependent upregulation of SPCA2 transcript with concurrent downregulation of mesenchymal markers and tumor cell migration characteristic of epithelial phenotype. Silencing SPCA2 abolished the ability of HDACi to reverse epithelial to mesenchymal transition (EMT). Independent of ATPase activity, SPCA2 elevated resting Ca2+ levels to activate downstream components of non-canonical Wnt/Ca2+ signaling. HDACi treatment led to SPCA2-dependent phosphorylation of CAMKII and -catenin, turning Wnt signaling off. We conclude that SPCA2 mediates the efficacy of HDACi in reversing EMT in TNBC by a novel mode of non-canonical Wnt/Ca2+ signaling. Our findings provide incentive for screening epigenetic modulators that exploit Ca2+ signaling pathways to reverse EMT in breast tumors.

Breast cancer develops from cells lining the milk ducts and slowly grows into a lump or a tumour. Breast cancer may be invasive or non-invasive. Invasive cancer spreads from the milk duct or lobule to other tissues in the breast, whereas, non-invasive ones lack the ability to invade other breast tissues. Non-invasive breast cancer is called in situ and may remain inactive for entire lifetime. Due to heterogeneity nature of breast, density as well as masses is variable in size and shape. A dataset of 18056 patients are collected from 20 Government Hospitals and 50 Private Hospitals in West Bengal before COVID-19 and after COVID-19. The classification of patients are made on three classes- Normal, Sign of Abnormality and Abnormality. The reports of MRIs of patients in January 2020 and February 2020 are collected from different hospitals. It is treated as dataset before COVID-19 . MRIS of patients in April 2020 and May 2020 are dataset during COVID-19. The entire datasets are accumulated for testing of any change in patients MRIS after the official announcement of new virus COVID-19 in March 2020. The aim of the paper is to make a comparison of any change in size and shape of masses of MRIs of patients before and after COVId-19. All collected MRIs reports are diagnosed by radiologists of hospitals.

Understanding the role of risk regions identified by genome-wide association studies (GWAS) have made considerable progress lately referred to the post-GWAS era. Annotation of the genes to the GWAS and fine-mapped functional variants, and understanding their biological pathway/gene networks enrichments is expected to give rich dividend by elucidating the mechanisms underlying prostate cancer. To this aim, we compiled and analysed currently available post-GWAS data on genes identified through GWAS and validated through experimental studies in prostate cancer to investigate molecular biological pathways enriched for assigned functional genes. The results highlight some well-known cancer signalling pathways, antigen presentation process and enrichment in cell growth and development gene networks suggesting prostate cancer may result from the accumulation of the effects of functional variants through multiple gene sets and pathways. The upstream analysis identifies critical transcription factors, which supplements the results regarding the regulatory role of the post-GWAS genes. We also identified the common genes between post-GWAS and three well-annotated prostate cancer Oncomine data in patient samples in order to uncover possible main genes in prostate cancer development/progression. Post-GWAS generated knowledge of gene networks and pathways, if analysed further and targeted appropriately, will have an important impact on clinical management of the disease.

Cancer is a leading cause of morbidity and mortality worldwide, yet much is still unknown about its mechanism of establishment and destruction. Recently, studies had shown that tumor cells cannot survive under the high temperature conditions. This treatment technique is called Hyperthermia. This report presents the case of radiative microwave heating of hyperthermia therapy on breast cancer in a porous medium. In this study, the steady state is solved analytically while unsteady state is solved using semi-implicit finite difference to get a more accurate prediction of blood temperature distributions within the breast tissues. A moderate temperature hyperthermia treatment is apply which results into cell death due to an increase in the level of cell sensitivity to radiation therapy and blood flow in tumor and oxygen. The results show that by applying metabolic heat generation rate of $3.97 X 10^{5}Wm^{-3}$, it takes upto 2 minutes for the tumor cells to get the require therapeutic temperature point.

Doxorubicin (DOX) is a frequently used chemotherapeutic drug for breast cancer, but its site specificity and local internalization into tumor cells is rather low. In this paper we conjugated magnetic nanoparticles (MNPs) with DOX and/or a pseudopeptide NucAnt (N6L) as modality to enhance DOX-induced antitumor effects in breast cancer cells (BT474). In this context, we determined cellular uptake of MNP formulations, analyzed cell viability and expression of apoptotic and cell cycle proteins after magnetic hyperthermia (43°C, 1 h) in vivo and in vitro. We have shown that i) the presence of N6L on the surface of DOX-functionalized MNPs increases their internalization into a target cells and potentiates the cytotoxic potential of the anticancer drug, ii) in combination with hyperthermia, DOX functionalized MNPs influence the expression of apoptotic and cell cycle proteins, and also favors tumor regression in vivo. Our data show that intratumoral application of DOX coupled MNPs is able to overcome biological barriers to chemotherapeutic drugs, enabling them to penetrate into the target cells. Combined with hyperthermia these MNPs can be an effective method in enhancing the localised delivery and penetration of DOX into breast cancer cells.

Lung cancer is almost the most common cause of cancer death in the world. Clinically, the conventional therapy to eradicate the cancer cells is chemotherapy but a better drug remains required. In this study, the effects of three bufadienolides, kalantuboside B, kalantuboside A and bryotoxin C, isolated from Kalanchoe tubiflora (Harvey) were evaluated and characterized in CL1-5 highly metastatic human lung cancer cells. Contrary to the apoptosis-promoting activity in other cancer cells, these three bufadienolides did not induce apoptosis in CL1-5 cancer cells. Instead, they activated an autophagy pathway, as indicated by the increase of autophagosomes formation. The induction of autophagy by these three bufadienolides was demonstrated to link to down-regulation of p-mTOR as well as up-regulation of LC3-II, ATG5, ATG7, Beclin-1. Moreover, among these three compounds, kalantuboside B in which a monosaccharide is attached at the bufadienolide aglycon, exhibited a better autophagy induction. Our findings revealed an alternative mechanism of drug action by bufadienolides in lung cancer cells and provided evidence for the possibility of treating highly metastatic human lung cancer through an autophagy pathway.

Accurate assessment of the breast cancer deterioration degree plays a crucial role in making medical plan, and the important basis for degree assessment is the number of mitoses in a given area of the pathological image. We utilized deep multi-scale fused fully convolutional neural network (MFF-CNN) combing with conditional random felid (CRF) to detect mitoses in hematoxylin and eosin stained histology image. Analyze the characteristics of mitotic detection ----scale invariance and sparsity, as well as the difficulties ---- small amount of data , inconsistent image staining and sample class unbalanced. Based on this, mitotic detection model is designed. In this paper, a tissue-based staining equalization method is used, and to establish an effective training sample set, we select training samples by using CNN. A mitotic detection model fusing multi-level and multi-scale features and context information was designed, and the corresponding training strategy was made to reduce over-fitting. As preliminarily validated on the public 2014 ICPR MITOSIS data, our method achieves a better performance in term of detection accuracy than ever recorded for this dataset.

Renal cell carcinoma (RCC) is the most common kidney cancer, accounting for approximately 80–90 % of all primary kidney cancer. Treatment for patients with advanced RCC remains unsatisfactory. Rare cancer stem cells (CSCs) are proposed to be responsible for failure of current treatment. Here, we investigate the effects of CBFA2T2 on CSCs regulation in RCC, as well as to elucidate the possible mechanisms. We showed that CBFA2T2 expression can significantly predict the survival of RCC patients. Functional assays showed that knocking-down of CBFA2T2 can inhibit cell migration and invasion in 786-O and A-498 cells in vitro, and reduce ALDH^high CSCs populations. Furthermore, CBFA2T2 expression is necessary for sphere-forming ability and cancer stem cells marker expression in RCC cell lines. Collectively, our data suggest that CBFA2T2 expression correlates with aggressive characteristics of RCC and CBFA2T2 is required for maintenance of “stemness” through regulation of stem cells factors, thereby highlighting CBFA2T2 as a potential therapeutic target for RCC treatment.

It is meaningful to monitor and identify the concrete cracks as they will seriously reduce the fatigue life of pavement. In this paper a new method based on distributed long-gauge optic fiber sensing is proposed to implement the crack identification. Firstly, the damage indicator, namely strain curve envelope area ratio (SCEAR), is proposed and calculated with the measured strain in time series when the plane goes across the pavement where the sensors are installed. Then the indicators with different sensors are normalization by the value of the indicator from one referenced sensor where damage normally will not happen. If the crack happens within the sensing gauge of the sensor, the value of damage indicator SCEAR from the sensor will increase. Therefore, the crack will be identified with the change of the damage indicator. The effect of the proposed method is first verified by some simulations of prefabricated pavement as the cracks can be accurately identified by the proposed method. Moreover, the influence from the aircraft, such as taxiing position, aircraft load and aircraft type, is not obvious enough to mislead the identification results. Lastly the static loading tests were implemented with one small-scale model of prefabricated concrete pavement in the lab. From the experimental results the prefabricated cracks inside the pavement slab can be identified accurately with the proposes method as the parameter SCEAR is increased by about 100% at the crack position, while it is only changed by about 3% at the undamaged position.

This paper systematically discusses the application of reinforcement learning in automatic driving system. Reinforcement learning frameworks show significant advantages in optimizing decision making, predictive perception, path planning, and controller design, exceeding the limitations of traditional supervised learning methods. The paper highlights the critical role of components such as scene understanding, positioning, and map making in autonomous driving systems, which provide reliable environmental awareness through deep learning and sensor fusion technologies to support intelligent decision-making in complex urban environments. In addition, the paper discusses innovative approaches to safety reinforcement learning to reduce risk in autonomous driving and ensure that systems adhere strictly to safety constraints while maximizing expected rewards. These findings provide an important theoretical and practical basis for further improving algorithm robustness, managing multi-agent interactions, and integrating ethical considerations in the future.

This study presents the design and comprehensive 3D multiphysics simulation of a novel microfluidic immunosensor for real-time, non-invasive monitoring of pro-inflammatory biomarkers in human sweat. The patch-like device, designed using COMSOL Multiphysics, integrates magnetofluidic manipulation with direct-field capacitive sensing. The sensor comprises two distinct units: an immunocomplex enhancement unit, employing a series of microcoils to optimize the binding efficiency, reaction kinetics, and homogeneity of biomarker-magnetic nanoparticle (MNP) interactions, thereby enhancing the sensor's specificity; and a layered capacitive sensing unit, designed to concentrate and detect biomarker-tagged MNPs, thus amplifying sensitivity. Simulations of the capacitive sensing unit revealed a substantial sensitivity increase of up to 42.48\% at an 85\% MNP concentration within the detection zone. These findings highlight the potential of the proposed immunosensor for efficient and precise real-time biomarker monitoring, which may facilitate early disease diagnosis and enable personalized healthcare interventions.

Vibration problems have become one of the most important factors affecting robot performance. To this end, a terminal residual vibration suppression method based on joint trajectory optimization is proposed to improve the accuracy and stability of robot motion. Firstly, based on the characteristics of the friction nonlinearity due to joint coupling and physical feasibility of dynamic parameters, a semidefinite programming method is used to identify dynamic parameters with actual physical meaning, thereby obtaining an accurate dynamic model. Then, based on the result of the residual vibration time domain analysis, a joint trajectory optimization model with the goal of minimizing joint tracking error is established. The Chebyshev collocation method is used to discretize the optimization model. The dynamic model is used as the optimization constraint, and barycentric interpolation is used to obtain the optimized joint motion trajectory. Finally, industrial robot experiments prove that the vibration suppression method proposed in this article can reduce the maximum acceleration amplitude of residual vibration by 62% and the vibration duration by 71%. Compared with the input shaping method, the method proposed in this paper can reduce the terminal residual vibration more effectively and ensure the consistency of running time and trajectory.

ABSTRACTCaffeine is known to impair both growth and development in the model social amoeba Dictyostelium discoideum. However, little is known about the transcriptional regulation in response to caffeine treatment in Dictyostelium. In yeast cells, caffeine mimics the effect of rapamycin in inhibiting mTORC1 activity. Here, we investigated whether changes in growth and development of Dictyostelium in the presence of caffeine or rapamycin are mediated by mTORC1 and/or mTORC2. Results: Treatment of wild type cells with caffeine or rapamycin resulted in severely impaired growth and in the formation of small aggregates in comparison to untreated cells. rip3‾ cells (lacking a mTORC2 component) and lst8‾cells (lacking a component of both mTOR complexes) showed higher and slower growth rates, respectively, in comparison to parental AX3 cells. Parental AX3 and rip3‾ cells displayed similar sensitivity to rapamycin and caffeine, while lst8‾ cells were more sensitive to these compounds. When developed in the presence of caffeine or rapamycin, AX3 cells formed aggregates after a long delay. Caffeine did not alter the morphology of small rip3‾ mounds and lst8‾ cells continued to remain solitary. However, in the presence of 1µM rapamycin rip3‾cells failed to form mounds while AX3 cells streamed and formed aggregates. Complementation of lst8‾ cells with the wild type lst8 gene rescued the aggregation phenotype. cDNA microarray analysis to uncover the spectrum of differentially regulated genes in response to caffeine treatment revealed 104 and 193 differentially expressed genes at 3-and 6-hours of development, respectively, in comparison to control cells. After 6 hours of starvation in the presence of caffeine, 25 genes encoding ribosomal proteins and 4 encoding elongation factors were up regulated. Furthermore, we identified that upon caffeine treatment at the 3- and 6-hours’ time points, 12 (10 up and 2 down) and 21 (13 up and 8 down) genes, respectively, encoding proteins involved in early development. Conclusion: We conclude that caffeine and rapamycin have similar effects in decreasing the growth rate and in reducing the aggregate size of D. discoideum. Studies with lst8‾ and rip3‾ cells suggest that these compounds affect cell growth and aggregation by acting on both mTOR complexes, mTORC1 and mTORC2. Analysis of the differentially expressed genes after caffeine treatment suggests a key role of these genes in growth and aggregation.

Although heart failure with preserved ejection fraction (HFpEF) has become the predominant heart failure subtype, it remains clinically under-recognized. This, has been attributed to the complex pathophysiological mechanisms that accompany individuals with several co-morbidities and symptoms and signs of HFpEF. Natriuretic peptides have been recognized to have important role in the diagnosis and monitoring of patients with heart failure with reduced ejection fraction (HFrEF), but their role in HFpEF remains controversial. Its seems that the role of NtproBNP in the diagnosis of HFpEF, is mainly driven by the pathophysiological characteristics of the patients.

The impact of antecedent soil moisture content on soil erosion is a complicated phenomenon, which is still under argument with contradictions in research results. Hence, the objective of this study is to investigate the impact of antecedent soil moisture content to soil loss on clay soil by conducting two-year field experiments under natural rainfall on runoff plots with length of 10 meters, width of 3 meters, and uniform slope of 9%. Volumetric soil moisture sensors were used to log soil moisture changes, and soil moisture readings were used along with rainfall records to quantify the antecedent soil moisture conditions for each rainfall event. Results of this study show duration of the effective erosion event outranks the antecedent volumetric soil moisture content. Field study also suggests that accumulative rain falling within 48 hours (Pp48) prior to an effective erosion event strongly correlated with soil loss per Rainfall-Runoff Erosivity Index (Soil Loss / EI30), particularly when the duration of an effective erosion event is either between 3 ~ 7 hours or 10~ 30 hours. Hence, Pp48 can be considered as an alternative to replace antecedent soil moisture content in RUSLE 2’s cover and management factor.

The control of the fine particle emission from the coal-fired power plants has been a big challenge in china. Either the conventional electrostatic precipitator or the fabric filter has some shortages. The electrostatic precipitator is hard to keep high efficiency for the submicron particles. The fabric filter could keep high efficiency but with very high pressure drop. One solution is to combine them together. Several types of hybrid particle collectors (HPC) combining the electrostatic precipitator and the fabric filter together have been developed and applied in a number of projects in China. In recent years, numerical simulation technology has been widely used in the design of the collectors. In this paper, an unsteady numerical model is used to investigate the particle deposition characteristics in a scale hybrid collector. The fluid field is modeled by using incompressible Navier-Stokes equations with the RNG turbulence equations. The corona discharge is solved by using a finite volume method. The particle charging is modeled by using a filed-diffusing combined model. And an unsteady cake formation model is used to simulate the filtration process.

Strong-aroma Baijiu is a traditional Chinese spirit distilled from grains that undergo solid-state fermentation. At the end of each fermentation cycle, a significant quantity of Huangshui accumulates at the bottom of the fermentation pit, constituting one of the primary by-products in the brewing process of strong-flavor liquor. In this report, the chemical component analysis of Huangshui obtained from a strong-flavor liquor factory revealed a diverse array of organic acids, alcohols, esters, starch, reducing sugars, amino acids, and other compounds present in Huangshui. Additionally, two specialized solid-state fermentation models were developed to investigate the formation process of Huangshui. Our findings demonstrate a positive correlation between the yield of Huangshui and the initial moisture content of fermented grains. It is concluded that Huangshui is the percolate produced during the solid-state brewing process of strong-flavor liquor, with its water content originating from the initial moisture of fermented grains.

Multimedia resources, such as instructional videos, are currently enjoying a certain popularity in training programmes for medical and dental students. The major challenge is to create such resources that have quality content and are acceptable to students. We investigated the opinions of a sample of 551 students from 4 medical universities in Romania in order to identify the characteristics of the instructional videos that students prefer and we comparatively analysed these characteristics according to gender, age group, but also according to their general preferences for using Internet services. We used univariate (hypothesis testing) and multivariate (Two-Step Clustering) data analysis techniques and revealed three clusters of students, primarily determined by perceptions of the visual appearance of instructional videos. The structure of the clusters by gender and age group is relatively similar, but we recorded differences between them associated with students' expressed preferences for certain Internet services compared to others. Students who prefer instructional videos to contain images used only for aesthetic purposes, to fill in breaks, use Internet services mainly for communication, while students who prefer in videos the use of already drawn explanatory diagrams are slightly younger than the others and use Internet services mainly for information and communication.

This literature review paper delves into the synergies between Climate-Smart Agriculture (CSA) and the effective management of food losses. With the escalating challenges posed by climate change and the pressing need to address food security concerns, the intersection of these two critical domains becomes paramount for sustainable agricultural practices. The review explores existing research on the implementation of climate-smart agricultural techniques and their impact on mitigating food losses throughout the agricultural value chain. The paper synthesizes findings related to climate-resilient crop varieties, precision farming, water-use efficiency, and sustainable soil management, highlighting their contributions to reducing post-harvest losses and enhancing overall food security. In addition to summarizing current knowledge, this paper identifies gaps in the literature and proposes avenues for future research. This review serves as a foundation for researchers, policymakers, and practitioners seeking to contribute to the advancement of climate-smart agriculture and the reduction of food losses, paving the way for a more sustainable and resilient global food system.

Based on the dynamic strength variation mechanism of concrete under complex loading conditions, two approaches were devised: numerical testing and CT scanning, guided by the principle of minimizing energy dissipation. A methodology for calculating concrete's failure area and measuring its strength was developed. The analysis delves into the mechanisms behind failure patterns and variations in concrete specimen strength, focusing on crack initiation, development, and the resultant failure surface formed by crack propagation, along with the stress distribution in concrete specimens subjected to diverse loading conditions. Through evaluating the strength and computed failure area of concrete specimens, it is evident that the loading method influences both the strength and failure area of concrete specimens. In general, a larger failure area correlates with a higher measured strength.

Detecting and monitoring changes in soil salinity through remote sensing provides an opportunity for field assessment in regions where on-site measurements are limited. This investigation, carried out in Siwa Oasis, Egypt, aimed to assess the efficacy of several soil salinity indices derived from Landsat 5 and 7 satellite images. To achieve this, 56 on-site ground measurements were utilized for evaluation purposes. The study aimed to improve the correlation between EC and index values and explore the relationship between salinity and changes in land cover. Eleven spectral indices were calculated for nine scenes captured in different months from August to December. The first approach involved stacking the data to identify the index with the strongest correlation with ground EC values, without the need for complex analysis or EC value ranging. In the second approach, the ground EC measurements were classified into seven different salinity categories, and the correlation coefficient was calculated between each index and each salinity category. The third approach analyzed the data temporally, considering different salinity levels. Lastly, a spatial correlation analysis was conducted between EC and index values in the fourth scenario. The initial approach revealed a weak correlation due to substantial variation in EC values. However, the SI index demonstrated the highest correlation coefficient of 0.38. In the second scenario, the S2 index exhibited the highest correlation of 0.96 for moderate salinity samples. The third scenario showed that the S1 index achieved the highest correlation value of 0.99 for moderately saline areas. In the fourth scenario, the SI index exhibited the strongest correlation among all four ponds with correlation coefficients of 0.23, 0.23, 0.18, and 0.61. Notably, the correlations observed in the second and third scenarios demonstrated higher correlation coefficients compared to both the first and fourth scenarios. The study highlighted significant variations in EC levels related to land cover types and pond elevation. Additionally, remote sensing methods detected a 48% increase in total vegetated area over 17 years, showing the potential of remote sensing techniques in salinity monitoring for expanding agriculture and improving land management.

Taeniid infections pose a significant threat to both animal and public health, as certain tapeworms within this group can also infect humans, potentially leading to severe health conditions. Therefore, this calls for preventive and control measures, such as regular deworming of dogs. While the efficacy of deworming has been established in developed countries, there is a paucity of reported deworming practices in rural areas of developing countries, such as Tanzania. This study aims to understand determinants for helminth treatment-seeking behavior towards control of cestodial taeniid infections in rural settings in northern Tanzania. A cross-sectional study was undertaken in agropastoral and pastoral areas of northern Tanzania. Comprehensive data from household surveys in selected sub-villages were collected to ascertain dog ownership, dog deworming practices, and the availability of dewormers. Analytical methods were employed to discern how various determinants influenced deworming practices among dog owners in these communities. Awareness of dewormers specifically formulated for dogs emerged as a pivotal factor affecting dog deworming practices. Dog owners who were informed about appropriate dog dewormers were nearly two times more likely to engage in deworming compared to those with limited knowledge (OR = 1.78, 95% CI 1.77 - 4.18, p < 0.001). A majority 32(51.6%, 95% CI: 38.7-64.3) acknowledged accessing dewormers for livestock within their wards. Praziquantel a potent dewormer on cestodes was least known to most dog owners 2(13%, 95% CI: 2.3-41.6). Praziquantel, a potent and common dewormer effective against cestodial taeniid infections, remains relatively unknown in rural areas of northern Tanzania. Therefore, more awareness on appropriate deworming agents against taeniids in dogs should be raised in rural dog-keeping communities.

The building envelope has the most significant contribution in the reduction of the building energy consumption. Application of new, alternative and improved materials and systems has an important impact on the buildings performances. This paper is focused on the thermal transmittance, as an indicator of the thermal conductance of the construction element. It includes comparisons of the U-values, calculated by software, with those measured in situ on three representative façade walls. The walls have been constructed with the new wall system Fragmat NZ-1, a new product in Macedonian buildings. This research provides basic information on the thermal transmittance of the system. The results of the analysis show that the in situ measuring is a useful tool in validation of the precision of analytically calculated values, since it was difficult to obtain precise results from the analytical calculations only, especially when the layers are with non-uniform thickness.

Seedling emergence is crucial for the establishment and growth of crops and is influenced by topsoil temperature and moisture. Mulching has been widely used to promote seedling emergence in areas with a cold spring. This study was conducted to determine and simulate the effects of transparent plastic film mulch on surface soil moisture, temperature, and seedling emergence of spring maize in Northwest China. Four treatments were used: no mulching (CK), full plastic film mulch (PMF), and partial plastic film mulch, 60 cm in width (PM60, 40 cm uncovered between rows of mulch) or 30 cm in width (PM30, 20 cm uncovered between rows of mulch). The effects of soil water conservation and temperature enhancement gradually decreased as the plastic film width decreased, but there was little difference between PMF and PM60 treatments. Soil-water-modified growing degree days (WGDD) described the beneficial effects of soil moisture and temperature with respect to seedling emergence under mulching conditions. Plastic film mulching markedly accelerated seedling emergence and increased final seedling emergence rate because mulching can shorten the autotrophy duration and maintain surface soil moisture, which leads to increased germination. The effects of seedling emergence improvement decreased as the plastic film width decreased. The relationship between WGDD and cumulative relative seedling emergence (CRE) was adequately described by a Gompertz function.

This paper introduces a novel framework for zero-shot learning (ZSL), i.e., to recognize new categories that are unseen during training, by distilling knowledge from foundation models. Specifically, we first employ ChatGPT and DALL-E to synthesize reference images of unseen categories from text prompts. Then, the test image is aligned with text and reference images using CLIP and DINO. Finally, the predicted logits are aggregated according to their confidence to produce the final prediction.Experiments are conducted on multiple datasets, including CIFAR-10, CIFAR-100, and TinyImageNet. The results demonstrate that our model can significantly improve classification accuracy compared to previous approaches, achieving AUROC scores above 96\% across all test datasets. Our code is available at https://github.com/1134112149/MICW-ZIC.

المستخلص تصنيع لقاح مكون من الحمض النووي الريبوزي الرسول الخاص بالبروتينات المسئولة عن انتاج البروتينات نيورامنيديز والهيم اجليوتونين لفيروسي الانفلونزا الخنازير والطيورمحاط بجزيئات دهنية بحجم النانوميتر عدوى انفلونزا الخنازير وانفلونزا الطيور مشكلة خطيرة تؤرق العالم كله هذه الايام خصوصا انها مميتة لكثير من اطفال العالم . بعد فترة التعافي من الاصابة تتكون المناعة المكتسبة ضدها لمدة عام تقريبا. هذه الانفلونزا تسبب تسمم فيروسي في الدم بالاضافة للالتهاب الرئوي وهذامن بين اكبرالاسباب للوفاة بين الاطفال قبل سن عامين عالميا بشكل مباشر. الهدف من الدراسة هو انتاج لقاح الحمض النووي الريبوزي الرسول من نوع الام بالنانوتكنولوجي لبروتينات الهيم اجليوتونين والنيورامنيديز الموجودة على سطح هذه الفيروسات التي تساعدتها في الاتصاق بالعائل الذي ستتكاثر داخل خلاياه بالجهاز التنفسي. هذه الدراسة دراسة استكشافية ومن خلالها استطاعنا تصميم هذا اللقاح باستعمال نظام توصيل للقاح بالنانوتكنولوجي حجم جزيئاته 70نانوميمتر. اللقاح الجديد اظهر فاعلية بنسبة 60% واظهر فاعلية حيوية مقاربة واثار جانبية اقل بالمقارنة باللقاحات المتوفرة حاليا بالسوق الدوائي ضد هذا النوع من الفيروسات الوبائية. ABSTRACT Background: Worldwide, Swine and Avian influenza, or the H1N1 and H5N1 serotypes of the Influenza A virus, is a highly contagious illness. In recent years, the global incidence of mortality rate has surpassed 284,000 fatalities. Aim of the study: The production of mRNA vaccine lipid nanoparticles (LNP) to combat the deadly strains of Avian and Swine influenza (H1N1 and H5N1 of the influenza A serotype). Methodology: Polymerase chain reaction (PCR) was used to clone genes of interest encoding Haemagglutinin (HA) and Neuraminidase (NA) of Influenza A virus strains (H5N1 and H1N1) known as Avian flu and Swine flu, respectively. The genes were then inserted using the EcoR1, BAM Hind II restriction endonuclease type II, and Ligase enzyme into the pET-21(+) transcription vector plasmid. On the other hand, the hybrid transcription vectors were mixed with T7 RNA polymerase and ribonucleotides within a test tube after being linearized using EcoR II. Following their purification via reversed-phase high-performance liquid chromatography (RP-HPLC), the mRNAs of the HA and NA were encased in 70 nm LNPs and subjected to reverse-phase high-performance liquid chromatography (RP-HPLC). Lastly, immunogenicity studies were performed in stages 1/2 of randomized human and preclinical clinical trials. Results: The bivalent vaccination had around 63% efficacy in preclinical studies and approximately 60% efficacy in randomized human clinical trials. As shown by the ELISA test, strong neutralizing antibodies against HA were prevalent. Conclusion: The current study is a promising effort because of the development of the novel LNP-mRNA vaccine, which could lower the incidence of Avian and Swine flu infectious disorders.

ABSTRACT Purpose: Tongue image analysis for disease diagnosis is an ancient traditional non-invasive diagnosis technique widely used by traditional medicine practitioners. Deep Learning based multi-label disease detection models offer tremendous potential to clinical decision support systems, by facilitating preliminary diagnosis. Methods: In this work, we propose a multi-label disease detection pipeline, where in observation and analysis of tongue images captured and received via smartphones assist in predicting the health status of an individual. All images are voluntarily given by subjects consulting collaborating physicians. Images thus acquired are first and foremost classified either into a diseased or a normal category by a 5-fold cross-validation algorithm using a convolution neural network (MobileNetV2) model for binary classification. Once the diseased label is predicted, the image is used to diagnose multiple diseases using the prediction algorithm based on DenseNet121. Results: Average accuracy of 93 % was achieved in classifying diseased from normal healthy tongue by detection model with MobileNetV2 architecture. Multilabel disease classification produced more than 90% accurate results for the seven class labels considered. Conclusion: AI based image analysis shows promising results and an extensive dataset could provide further improvements to this approach. Rather than employing high-cost sophisticated image capturing setup, experimenting with smartphone images opens opportunity to provide preliminary health status to individuals on smartphone prior to further line of treatment and diagnosis.

In an effort to enhance the efficiency and safety of open-pit mines, this study explores the optimization of end slope road parameters and slope structures, specifically focusing on unmanned driving lanes.A significant aspect of the study is the development of a truck trajectory offset model, which considers the different reaction times between automated sensors and human drivers in adapting to environmental changes. To test these concepts, the study uses numerical simulations to confirm the stability of the proposed end slope designs. Using Victory West Mine No. 1 as a case study, the research determines the optimized width for unmanned driving lanes and the maximum angle for safe steepening of end slopes. The findings indicate that the optimized unmanned lane width for NTE240 mining dump trucks is 1743 mm, allowing for a 2-degree increase in the slope angle at the south end slope. This optimization leads to a steep mining stripping volume of 3.2735 million m³ and a coal output of 2.49628 million tons, maintaining a stripping ratio of 1.31m³/t. These results demonstrate that the unmanned driving road width optimization not only ensures slope safety but also significantly boosts the economic benefits of steep mining in open-pit mines.

In the present work report, the MgAl₂O₄and the Ag/MgAl₂O₄ samples were successfully synthesized by the modified hydrothermal and the isovolumetric impregnation methods, respectively. The structural properties of the prepared samples were systematically characterized by XRD, SEM, TEM, DRS, XPS and et al techniques. The photocatalytic degradation of methylene blue by the Ag/MgAl₂O₄ and MgAl₂O₄ samples was comparatively studied under UV lamp irradiation. The results revealed that the prepared Ag/MgAl₂O₄ (pH=6) samples were the most active among the samples in photocatalytic of methylene blue. Under UV lamp irradiation, the Ag/MgAl₂O₄ (pH=6) photodegradation of methylene blue reached to 89.6% within 120 min. And the Ag/MgAl₂O₄ (pH=6) complex photocatalysts displayed a high photochemical stability under repeated irradiation. Repeated irradiate the Ag/MgAl₂O₄ (pH=6) compound, which indicated it had a high photochemical stability.