Background. 46,XX disorders of sex development are rare. Approximately, 90% of XX males are SRY-positive, while testicular development in the absence of SRY takes place in a minority. Methods: A boy with 46,XX karyotype (SRY-negative; absence of SOX9 duplications) was investigated by targeted Next Generation Sequencing (NGS), Multiplex ligation-dependent probe amplification (MLPA), and Comparative Genomic Hybridization array (CGH-array). Results: The boy had normal male phenotype and normal prepubertal values of testicular hormones. He presented a heterozygous duplication of 49.626 bp, encompassing exons 2 and 3 of DMRT1. The result was arr[GRCh37] 9p24.3(845893_895518)x3. Since both breakpoints are harbored in the intronic regions, the duplication does not stop or shift the coding frame. Additional known pathogenic or uncertain variants in pro-testis gene cascade were not identified. Conclusions: This study report a boy with 46,XX testicular disorder of sex differentiation, showing a de novo partial intragenic duplication of DMRT1. This intragenic duplication may result in a gain of function, acting as primary pro-testis gene (or anti-ovary gene) in a 46,XX human foetus and permitting normal pre-pubertal endocrine testis function.

(1) Background: Mpox was declared an international public health emergency by WHO. Initially, Smallpox vaccine in Italy was offered only to laboratory personnel at direct risk of infection. Currently, Healthcare workers (HCWs) are all considered by European Centre for Disease Prevention and Control (ECDC) to be at low or moderate risk. (2) Methods: To assess smallpox vaccination coverage among HCWs in an Italian hospital with different levels of risk of exposure to Mpox infection and to assess their attitudes toward vaccination, a self-report was administered to HCWs stratified at high and low/moderate risk. (3) Results: Of the 338 HCWs evaluated, 60.36% provided the requested data; among them the percentage of previously vaccinated staff was 38.7%, which corresponds to 23.4% of the total HCWs in the departments considered. Considering those born before 1979 as vaccinated, vaccination coverage increases from 23.4% to 41.4%. The department with the highest percentage of vaccinated is infectious diseases (60.5%); The percentage of HCWs who adhered to vaccination is 23%; only 8.8% of laboratory staff want to vaccinate, compared with 100% of midwives. The department with the highest percentage of vaccination adherence is proctology (85.7%). (4) Conclusions: Given the vaccination adherence rate and the vaccination coverage of the departments analyzed, it would be useful to extend vaccination against Smallpox to frontline HCWs involved in patient care in Italy too.

Background and Aims: The present study analyzed retrospectively the association between socioeconomic deprivation and graft and patient survival in a cohort of 2,568 adult recipients of a liver transplant between 1996 and 2022. Materials and methods: The primary exposure was a nationally validated socioeconomic deprivation index (DI) at census block level and ranking from 1-5, with higher ranks indicating more significant socioeconomic deprivation. Results: At a median (IQR) follow-up of 144.8 (204) months, the overall patient and graft survival rates were 92% and 90.4% at 1 year, 78.4% and 72.2% at 5 years, and 58% and 56.7% at 10 years. Recipients with a DI rank above the median (i.e., more deprived) had 1, 5, and 10-year patient and graft survival rates of 91% and 89.5%, 70.4% and 68.4%, 48% and 46.7%, respectively, versus 92% and 90.4%, 78.4% and 72.2%, and 58% and 56.7% for less deprived patients (log-rank p<0.001). More deprived patients had a higher risk of death (p<0.0001), hypertension (p<0.0001), obesity (p=0.02), diabetes mellitus (p=0.02), graft rejection (p<0.0001), chronic kidney dysfunction (p<0.0001), major cardiovascular events (p<0.0001) and de novo malignancies (p<0.0001) than less deprived recipients. The factors associated with the survival probability were younger donor and recipient ages (p=0.03 and 0.02, respectively), female recipient sex (p=0.04), absence of HCV (p<0.01), absence of HCC (p=0.02), absence of DM at transplantation (p=0.03) and 1 year (p=0.01), lower DI (p=0.02), lower MELD (0.02), shorter CIT (p=0.03), TAC (p=0.01), and EVR in the immunosuppressive regimen (p=0.02). Conclusions: Patients from more deprived areas have a higher risk of death after liver transplantation. Pre- and post-transplant socioeconomic risk profiling is warranted to better tailor care to patient’s needs and expectations.

We conducted a hybrid-design study on a historical cohort of 359 adult recipients of a liver graft who received transplants between 1996 and 2002. The study aimed to identify predictors of survival and investigate the prevalence of co-morbidities among long-term survivors. The actuarial (95% CI) patient survival of the overall study cohort was 96% (94.6%-98.3%), 69% (64.2%-73.6%), 55% (49.8%-59.9%), 42.8% (37.6%-47.8%), and 34% (29.2%-38.9%) at 1, 5, 10, 15, and 20 years, respectively. The actuarial (95% CI) graft survival was 93.8% (91.6%-97.2%), 67.6% (62.2%-71.5%), 54.3% (49.6%-59.3%), 42.1% (37.3%-47.4%), and 33.8% (29.0%-38.4%) at 1, 5, 10, 15, and 20 years, respectively. The leading cause of death was hepatitis C virus recurrence (24.6%), followed by extrahepatic malignancies (16.9%), infection (14.4%), and hepatocellular carcinoma recurrence (14.4%). The Cox proportional hazards analysis revealed that several independent factors were associated with the survival probability. These factors include younger donor and recipient ages (p=0.001 and 0.004, respectively), female recipient sex (p<0.001), absence of HCV (p<0.01), absence of HCC (p=0.001), and absence of diabetes mellitus at one year (p<0.01). At the latest follow-up, the leading comorbidities in the long-term survivors were hypertension (53.6%), obesity (18.7%), diabetes mellitus (17.1%), hyperlipidemia (14.7%), chronic kidney dysfunction (14.7%), and extrahepatic malignancies (13.8%), with 73.9% of patients having more than one complication. The Kaplan-Meier probability (95% CI) of complication-free survival was 65.4% (60.2%-70.3%), 38.4% (33.4%-43.7%), 17.8% (14.1%-22.2%), 7.2% (4.8%-10.5%), and 1.94% (0.85%-4.15%) at 1, 5, 10, 15, and 20 years, respectively. Aging with a liver graft is associated with an increased risk of complications and requires ongoing care to reduce the long-term attrition rate resulting from chronic immunosuppression.

To obtain long-term data on the use of everolimus in patients who underwent liver transplantation for hepatocellular carcinoma, we conducted a retrospective, single-center analysis of adult recipients transplanted between 2013 and 2021. Patients on everolimus-incorporating immunosuppression were matched with those on tacrolimus using an inverse probability of treatment weighting methodology. Two propensity-matched groups of patients were thus compared: 233 (45.6%) receiving everolimus versus 278 (54.4%) on tacrolimus. At a median (interquartile range) follow-up of 4.4 (3.8) years after transplantation, everolimus patients showed a reduced risk of recurrence versus tacrolimus (7.7% versus 16.9%; RR=0.45; P=0.002). At multivariable analysis, microvascular infiltration (HR=1.22; P<0.04) and a higher tumor grading (HR=1.27; P<0.04) were associated with higher recurrence rate while being within Milan criteria at transplant (HR=0.56; P<0.001), a successful pre-transplant downstaging (HR=0.63; P=0.01) and use of everolimus (HR=0.46; P<0.001) had a positive impact on the risk of post-transplant recurrence. EVR patients with earlier drug introduction (30 days; P<0.001), longer treatment duration (P<0.001), and higher drug exposure (5.9ng/mL; P<0.001) showed lower recurrence rates versus TAC. Based on our experience, everolimus provides a reduction of the relative risk of hepatocellular carcinoma recurrence, especially for advanced-stage patients and those with earlier drug administration, higher drug exposure, and longer time on treatment. These data advocate for early everolimus introduction after liver transplantation to reduce the attrition rate consequent to chronic immunosuppression.

Human pose estimation is a complex detection task in which the network needs to capture the rich information contained in the images. In this paper, we propose MSTPose (Multi-Scale Transformer for human Pose estimation). Specifically, MSTPose leverages a high-resolution Convolution neural network (CNN) to extract texture information from images. For the feature maps from three different scales produced by the backbone network, each branch performs the coordinate attention operations. The feature maps are then spatially and channel-wise flattened, combined with keypoint tokens generated through random initialization, and fed into a parallel Transformer structure to learn spatial dependencies between features. As the Transformer outputs one-dimensional sequential features, the mainstream two-dimensional heatmap method is abandoned in favor of one-dimensional coordinate vector regression. The experiments show that MSTPose outperforms other CNN-based pose estimation models and demonstrates clear advantages over CNN + Transformer networks of similar types.

Nanosystems-based antifungal agents have emerged as an effective strategy to address issues related to drug resistance, drug release, and toxicity. Among the different materials used for drug delivery, multifunctional polymers have proven to be ideal due to their versatility. This review provides an overview of the various types of nanoparticles used in antifungal drug delivery systems, with a particular emphasis on the types of polymers used. The review focuses on the application of drug delivery systems and the release behavior of these systems. Furthermore, the review summa-rizes the critical physical properties and relevant information utilized in antifungal polymer nanomedicine delivery systems, and briefly discusses the application prospects of these systems.

Gender Identity Dysphoria (GID) is a condition characterized by a strong and persistent identification with the opposite sex. These people consider themselves victims of a sort of biological accident: "a soul in a wrong body". There are numerous theories on the origin of transsexualism: genetic, hormonal and psychological causes have been hypothesized, but those currently most accredited are the neuroanatomical ones. The cornerstones of hormone conversion therapy (Gender Affirming Hormone Therapy, GAHT) are feminizing hormones for transgender women (MtFs) and virilizing for transgender males (FtMs). GID can be present among adolescents and older people. For adolescents is now accepted reversible treatment of puberty withdrawal with hormones that stops the progression of pubertal development in the biological direction not accepted; for elderly people is suggested GAHT in reduced doses. Physicians should consider and discuss with people with GID about fertility preservation, general and cancer risks. We present also data of 127 transsexual patients enrolled at the Garibaldi-Nesima Andrology Clinic in Catania (Italy) from 2003 to 2020. To optimize the conversion treatment with sex hormones, transsexuals require long-term follow-up. GAHT must be performed by a doctor who is familiar with these problems. Therefore, the “do-it-yourself” trend and the lack of medical and laboratory checks over time should be absolutely discouraged. Before proceeding with the surgical sex reassignment, it is recommended to refer to an endocrinologist and psychologist or psychiatrist for a period of 2-3 years. The transition surgical conclusion process must be practiced by a quality surgical team.

Contrary to optical images, Synthetic Aperture Radar (SAR) images are in different electromagnetic spectrum where the human visual system is not accustomed to. Thus, with more and more SAR applications, the demand for enhanced high-quality SAR images has increased considerably. However, high-quality SAR images entail high costs due to the limitations of current SAR devices and their image processing resources. To improve the quality of SAR images and to reduce the costs of their generation, we propose a Dialectical Generative Adversarial Network (Dialectical GAN) to generate high-quality SAR images. This method is based on the analysis of hierarchical SAR information and the “dialectical” structure of GAN frameworks. As a demonstration, a typical example will be shown where a low-resolution SAR image (e.g., a Sentinel-1 image) with large ground coverage is translated into a high-resolution SAR image (e.g., a TerraSAR-X image). Three traditional algorithms are compared, and a new algorithm is proposed based on a network framework by combining conditional WGAN-GP (Wasserstein Generative Adversarial Network - Gradient Penalty) loss functions and Spatial Gram matrices under the rule of dialectics. Experimental results show that the SAR image translation works very well when we compare the results of our proposed method with the selected traditional methods.

Embryo and fetus grow in a hypoxic environment. Intrauterine oxygen levels fluctuate throughout the pregnancy allowing the oxygen to modulate apparently contradictory functions, such as the expansion of stemness but also differentiation. We have recently demonstrated that in the last weeks of pregnancy oxygenation progressively increases, but the trend of oxygen levels during the previous weeks remains to be clarified. In the present study, umbilical venous and arterial oxygen levels, fetal oxygen extraction, oxygen content, CO2, and lactate were evaluated in a cohort of healthy newborns with gestational age &lt; 37 weeks. A progressive decrease in pO2 levels associated with a concomitant increase in pCO2 and reduction of pH has been observed starting from the 23rd week until approximately the 33-34th week of gestation. Over this period, despite the increased hypoxemia, oxygen content remains stable thanks to increasing hemoglobin concentration, which allows the fetus to becoming more hypoxemic, but not more hypoxic. Starting from the 33-34th week, fetal oxygenation increases and ideally continues following the trend recently described in term fetuses. The present study confirms that oxygenation during intrauterine life continues to vary even after placenta development, showing a clear biphasic trend. Fetuses, in fact, from mid-gestation to near-term become progressively more hypoxemic. However, starting from the 33-34th week, oxygenation progressively increases until birth. In this regard, our data suggest that the placenta is the hub that ensures this variable oxygen availability to the fetus, and we speculate that this biphasic trend is functional to the promotion, in specific tissues and at specific timing, of stemness and intrauterine differentiation.

In-depth research on the rehabilitation mechanism and motion characteristics of a rehabilitation training robot based on 4-UPUS parallel mechanism. The overall design and the working principle of each key component are explained, and the robot rehabilitation scheme is described. The static analysis and modal analysis of the robot bearing structure are carried out to verify whether the static mechanical characteristics of the mechanism meet the application requirements under working conditions.A simplified mathematical model of the six-bar linkage mechanism is established, and the kinematics of the mechanism is solved by the geometric analysis method. The motion characteristic diagram of each key point is obtained through simulation calculation. Establish the motion model of the parallel mechanism, and discuss the working space and motion performance analysis of the mechanism. The forward solution analysis of the mechanism position is carried out by using the numerical analysis method, and the three-dimensional graphics of the attitude angle and linear displacement of the reachable working space are obtained.Taking the UPUS single branch chain as the analysis object, the single open chain analysis method is used to solve the kinematics image of the corresponding surface in the working space of the mechanism, which verifies the correctness of the kinematics theoretical solution and the feasibility of simulation.The research results show that the 4-UPUS parallel mechanism rehabilitation training robot can cooperate with the ankle joint for rehabilitation training. It makes up for the single movement of the current lower limb rehabilitation robot and the unsatisfactory rehabilitation effect, and provides a reference for the practical application of the subsequent ankle joint rehabilitation robot system.

Fast 3D reconstruction with semantic information on road scenes is of great requirements for autonomous navigation. It involves issues of geometry and appearance in the field of computer vision. In this work, we propose a method of fast 3D semantic mapping based on the monocular vision. At present, due to the inexpensive price and easy installation, monocular cameras are widely equipped on recent vehicles for the advanced driver assistance and it is possible to acquire semantic information and 3D map. The monocular visual sequence is used to estimate the camera pose, calculate the depth, predict the semantic segmentation, and finally realize the 3D semantic mapping by combination of the techniques of localization, mapping and scene parsing. Our method recovers the 3D semantic mapping by incrementally transferring 2D semantic information to 3D point cloud. And a global optimization is explored to improve the accuracy of the semantic mapping in light of the spatial consistency. In our framework, there is no need to make semantic inference on each frame of the sequence, since the mesh data with semantic information is corresponding to sparse reference frames. It saves amounts of the computational cost and allows our mapping system to perform online. We evaluate the system on naturalistic road scenes, e.g., KITTI and observe a significant speed-up in the inference stage by labeling on the mesh.

(1) Background: Persistent postural-perceptual dizziness (PPPD) is a syndrome described as secondary when it is the consequence of an organic disorder (s-PPPD) or primary when no somatic triggers cannot be identified. We evaluated a group of patients diagnosed as s-PPPD with Benign Positional Paroxysmal Vertigo (BPPV) as the main somatic trigger with the aim to identify predictive clinical elements of evolution towards PPPD.; (2) Methods: We compared the clinical characteristics of the 51 patients with s-PPPD having as trigger a BPPV (group 1) with 107 subjects diagnosed as BPPV but with no evolution in PPPD (control group). Results: A significant statistical difference in the mean age was found between s-PPPD and the non-s-PPPD group. The latency between the onset of BPPV and the final diagnosis was 25.2 days in the group 1 and 12.8 days in the control group; (4) Conclusions: The parameters mostly involved as potential precipitants of PPPD after BPPV are represented by the age of the patients and a long latency between the onset of BPPV and the final diagnosis: the mean age of the subjects who developed a PPPD following BPPV is significantly higher. These findings lead us to emphasize the importance of an early identification and treatment of BPPV, especially in older patients.

The surface defects of shield subway tunnel can significantly affect the serviceability of the tunnel structure and may compromise the operation safety. To effectively detect the multiple surface defects, this research employs a tunnel inspection trolley (TIT) based on the mobile laser scanning technique. By conducting the inspection of the shield tunnel on a metro line section, various surface defects are identified by the TIT, including water leakage defect, dislocation, spalling, cross-section deformation, etc. To explore the root causes of the surface defects, the association rules between different defects are calculated via an improved Apriori algorithm. Results show that: i) there are significant differences in different association rules of various surface defects of the shield tunnel; ii) the average confidence of the association rule “dislocation &amp; spalling → water leakage” is as high as 57.78%, indicating that most of the water leakage defects are caused by dislocation and spalling of the shield tunnel in the sections being inspected; iii) the weakest rule appears at “water leakage → spalling”, with the average confidence of 13%. The association analysis can be used in predicting the critical defects influencing the structural reliability and operation safety, such as water leakage, and optimizing the construction and maintenance work for the shield subway tunnel.

Microplastics pollution in sugarcane areas of China is severe, and reducing their ecological risks is critical. This study aims to explore the effects and mechanisms of microplastics combined with or without biochar on sugarcane growth, soil biochemical properties in red soil by a potted experiment. The results showed that compared with control (CK), microplastic alone treatments reduced the dry biomass of sugarcane, soil pH and the nitrogen (N) and phosphorus (P) contents, obviously decreased the observed_OTUs, Chao1 and Shannon indices of soil total bacteria (16S rRNA gene-based bacteria) while increasing them in phoD-harbouring bacteria. Interestingly, microplastics combined with biochar could alleviate the negative effects of microplastic accumulation on sugarcane growth and soil quality. There were significant differences in the bacterial community compositions among different treatments. Compared with CK, all other treatments significantly decreased the relative abundance of Gemmatimonadota while only microplastic combined with biochar treatments significantly increased the abundance of Subgroup_10 for the 16S rRNA gene, and only microplastic alone treatments significantly increased the relative abundance of Streptomyces for the phoD gene. Moreover, the treatments with microplastics combined with biochar increased the relative abundance of Subgroup_10 and Bradyrhizobium while decreased the IMCC26256 and Streptomyces compared with that in the treatment with microplastics alone. Correlation analysis showed that Subgroup_10 and Bradyrhizobium were significantly positively correlated with sugarcane biomass and several soil properties, while IMCC26256 and Streptomyces were just the opposite. Additionally, different treatments also changed the abundance of potential microbial functional genes. Compared to CK, other treatments increased the abundance of aerobic_ammonia_oxidation, denitrification while decreased the abundance of nitrate_respiration, nitrogen_respiration; meanwhile, these four functional genes involved in N cycling processes were obviously higher in treatments with microplastics combined with biochar than in treatments with microplastic alone. In conclusion, microplastics combined with biochar could alleviate the negative effects of microplastic accumulation on sugarcane growth by improve soil nutrients and microbial community structure and function.

The secondary structures of Scherer commonly known as perineuronal and perivascular satellitosis have been identified as a histopathological hallmark of diffuse, invasive, high-grade gliomas. They are recognized as perineuronal satellitosis when clusters of neoplastic glial cells surround neurons cell bodies and perivascular satellitosis when such tumour cells surround blood vessels infiltrating Virchow-Robin spaces. In this review, we provide an overview of emerging knowledge regarding how interactions between neurons and glioma cells can modulate tumour evolution and how neurons play a key role in glioma growth and progression, as well as the role of perivascular satellitosis into mechanisms of glioma cells spread. At the same time, we review the current knowledge about the role of perineuronal satellitosis and perivascular satellitosis within the tumour microenvironment (TME), in order to highlight critical knowledge gaps in research space.

Fructus Amomi (FA) is usually regarded as the dried ripe fruits of Amomum villosum Lour. (FAL) or Amomum villosum Lour. var. xanthioides T. L.Wu et Senjenis (FALX) However, FAL, which always has a much higher price because of its better quality, is confused with FALX in the market. As volatile oil is the main constituent of FA, a strategy of chromatography-mass spectrometry (GC-MS) and chemometric approches was applied to compare the chemical composition of FAL and FALX. The results showed that the oil yield of FAL was significantly higher than that of FALX. Total ion chromatograph (TIC) showed that cis-nerolidol existed only in FALX. Bornyl acetate and camphor, could be considered as the most important ones in FAL and FALX respectively. Moreover, hierarchical cluster analysis (HCA) and principal component analysis (PCA) successfully distinguished the chemical constitutes of the volatile oils in FAL and FALX. Additionally, bornyl acetate, α-cadinol, linalool, β-myrcene, camphor, d-limonene, terpinolene and endo-borneol were selected as the potential markers for discriminating FAL and FALX by partial least squares discrimination analysis (PLS-DA). In conclusion, this present study first developed a scientific approach to separate FAL and FALX based on volatile oils by GC-MS combined with chemometric techniques.

Soil cadmium (Cd) contamination has become a serious problem in China. In this study, the goals of the field experiments were to understand how the application of nitrogen fertilizer at the full heading stage and filling stage reduced the uptake of Cd in rice by affecting the distribution of Cd in iron plaques on the root surfaces and subcellular in the root and flag leaf. The hydroponic culture experiments aimed to explore the effect of interaction or deficiency of nitrogen and cadmium on cadmium accumulation in rice at the late growth stage. The results showed that under the condition of having enough nitrogen supply during the early growth stage, applying nitrogen fertilizer during the full heading stage and filling stage resulted in a significant increase in the concentration of Fe and Cd on the root plaques at the milk stage and mature stage. Additionally, it increased the concentration and proportion of Cd in the soluble fraction of subcellular in the flag leaves at the milk stage. On the other hand, when there was a deficiency of nitrogen, the concentration of Fe in the root plaques increased significantly, while the concentration of Cd in the root plaques decreased significantly. Moreover, the proportion of Cd in the flag leaf cell walls increased significantly. Regardless of whether there was sufficient or deficient nitrogen supply during the early growth stage, applying nitrogen at the full heading stage reduced the Cd concentration in brown rice by 35.11% and 57.25%, respectively. Under hydroponic culture conditions with both Cd exposure and later-stage nitrogen supply significantly increased the Cd concentration in brown rice. However, in the absence of Cd, nitrogen supply significantly reduced the Cd concentration in brown rice. The accumulation of Cd in brown rice was significantly correlated with the accumulation of Fe and Mn at the late growth stage. Our findings indicate that when there is sufficient nitrogen nutrition during the early growth stage of rice, topdressing nitrogen fertilizer at the full heading stage combined with lime with mineral element fertilizers such as Fe and Mn is an effective approach to reduce the presence of cadmium in rice grains.

Coptisine (Cop) exerts a neuroprotective effect in central nervous system disease, particularly ischemic stroke. However, its protective mechanism is still unclear. This study aimed to investigate the protective effect of Cop on cerebral ischemia-reperfusion (IR) rats with a middle cerebral artery occlusion model by integrating a gas chromatography-mass spectrometry (GC-MS) based metabolomics approach with biochemical assessment. Our results showed that Cop could improve neurobehavioral function and decrease the ischemia size in IR rats. In addition, Cop was found to decrease inflammatory mediators (e.g., prostaglandin D2 (PGD2) and tumor necrosis factor-α (TNF-α) and attenuate oxidative stress response (e.g., increase the superoxide dismutase (SOD) expression and decrease 8-iso-PGF2α level). Furthermore, GC-MS based cerebrospinal fluid (CSF) metabolomics analysis indicated that Cop influenced the level of glycine, 2,3,4-trihydroxybutyric acid, oleic acid, glycerol, and ribose during IR injury. Cop exhibited a good neuroprotective effect against cerebral IR injury and metabolic alterations which might be mediated through its antioxidant and anti-inflammatory property.

Faced with difficulties stemming from the complex interactions between tight gas sand bodies and fractures when describing and identifying reservoirs, a composite reservoir model was established. By setting the supply boundary to characterize the superposition characteristics of sand bodies, a mathematical model of unstable seepage in fractured vertical wells in tight sandstone gas reservoirs was constructed considering the factors such as stress sensitivity, fracture density and fracture symmetry. The seepage law and pressure response characteristics of gas well in tight sandstone discontinuous reservoir with stress sensitivity, semi-permeable supply boundary and complex fracture topology were determined, and the reliability of the model was verified. The research results more accurately depict the pressure characteristic curve of the superposed sand body complex fracture vertical well, and provide a more comprehensive model for tight gas production dynamic analysis and well test data analysis, which can more accurately guide the dynamic inversion of reservoir and fracture parameters.

Due to increasing concerns about global warming and energy crisis, intensive efforts have been made to explore renewable and clean energy sources. Single-atom metals and two-dimensional (2D) nanomaterials have attracted extensive attention in the fields of energy and environment because of their unique electronic structures and excellent properties. In this review, we sum-marize the state-of-art progress on the single-atom metal supported at 2D MoS2 (single-atom metal/2D MoS2) for electrochemical CO2 reduction and water splitting. First, we introduce the advantages of single-atom metal/2D MoS2 catalysts in the fields of electrocatalytic CO2 reduction and water splitting, followed by the strategies for improving electrocatalytic performances of single-atom metal/2D MoS2 hybrid nanomaterials and the typical preparation methods. Further, we discuss the important applications of the nanocomposites in electrocatalytic CO2 reduction and water splitting via some typical examples, particularly focusing on their synthesis routes, modification approaches, and physiochemical mechanisms for improving their electrocatalytic performances. Finally, our perspectives on the key challenges and future directions of exploring high-performance metal single-atom catalysts are presented based on recent achievements in the development of single-atom metal/2D MoS2 hybrid nanomaterials.

The active layer thickness (ALT) is affected by local soil material and surface vegetation coverage in Tibetan plateau permafrost region. The human activities and engineering construction along the Qinghai-Tibet Highway (QTH) destroyed the surface vegetation coverage, which have seriously influenced the ALT and heat exchange balance. Meanwhile, the changes of the detailed internal structure in the active layer will affect the stability of engineering infrastructure. Ground-penetrating radar (GPR) was used to detect the ALT in the permafrost region. However, researches on the detailed structure of the active layer and spatial variation information of ALT are rare, the main reason given for this is that the lack of advanced imaging techniques to enhance the GPR images. In this paper, the researchers focus on solving this problem by applying the reverse time migration (RTM) method to GPR field data acquired in the Beiluhe region. Analyses of the results led to conclusions as follows: a) The RTM algorithm is proved to be accurate for imaging the characteristics of the active layer through the dielectric constant model obtained by common midpoint and GPR data velocity analysis. b) The result of RTM profiles show the loose structure and graben-like fine internal structure. Combining with drill data and soil materials information, the researchers deduce the graben-like structure might be coarse gravel layer, which may be related to subgrade settlements in some local area. c) The 2D contour maps not only show the spatial variation feature of ALT at two sides of the highway, but also can compensate the defect of the research for single 2D survey line. The ALT is about 0.6~0.8 m in most areas, and about 0.8~0.9 m near the highway at west side of the QTH on the 2D contour maps. From the RTM interpretation profile, the closer to the plash, the deeper thawed active layer. The detailed internal structure of the active layer and 2D contour maps of ALT have great significance for the study of fine internal structure and the characteristic of ALT spatial variation in the Tibetan plateau under the background of climatic change.

Type two diabetes mellitus (T2DM) represents a chronic condition with increasing prevalence worldwide among the older population. T2DM condition increases the risk of micro and macro-vascular complications as well as the risk of geriatric syndromes as falls, fractures and cognitive impairment. The management of T2DM in the older population represents a challenge for the cli-nician, and a Comprehensive Geriatric Assessment should always be prioritized, in order to tailor the glycate haemoglobin target according to functional and cognitive status comorbidities, life ex-pectancy and type of therapy. According to the most recent guidelines, older adults with T2DM should be cathegorized in three groups: healthy patients with good functional status, patients with complications and reduced functionality and patients at the end of life; for each group the target for the glycemic control is different, also according to the type of treatment drug. The therapeutic ap-proach should always begin with lifestyle changes; after that, several lines of therapies are available, with different mechanism of action and potential effect other than glucose level reduction. Partic-ular interest is growing around sodium-glucose cotransporter-2 inhibitors, due to their effect on the cardiovascular system. In this review we evaluate the therapeutic options available for the treat-ment of older diabetic patients, to ensure a correct treatment approach

Abstract: Over the years, several distinct pathogenic coronaviruses have emerged, including the pandemic SARS-CoV-2 which is difficult to curtail despite the availability of licensed vaccines. The difficulty in managing SARS-CoV-2 is linked to changes in the variants’ proteins, especially in the spike protein (S) used for viral entry. These mutations, especially in the S, enable the virus to evade the immune responses induced by natural infection or vaccination. However, some parts of the SP in the S1 subunit and the S2 subunit are considered conserved among coronaviruses. In this review, we will discuss the epitopes in the SARS-CoV-2 S1 and S2 subunit proteins that have been demonstrated by various studies to be conserved among coronaviruses and may be immunogenic for the development of vaccine. Considering the higher conservancy of the S2, we will further discuss the likely challenges that could limit the S2 subunit from inducing robust immune responses and the promising approaches to increase their immunogenicity.

In rice, symbiotic N fixation via nodule bacteroids does not take place naturally. Although N fixation by endophytic and associative diazotrophs has been reported in rice, main organs and seasonal regulation for the N fixation have not been elucidated. In this study, therefore, seasonal changes of nitrogenase (acetylene reduction) activity and carbohydrate contents in culm internode (IN), basal nodes (BN), and crown root (CR) were investigated in manure compost (MC)- and chemical fertilizer-applied rice. Nitrogenase activity increased after rooting, and reached the highest activity in BN of MC-applied rice at panicle initiation. In BN of MC-applied rice, the sucrose content was low whereas the higher glucose content was detected at panicle initiation. Although bacterial and diazotrophic bacterial populations were most abundant in CR, the nitrogenase activity seemed to be restricted by its trace sucrose and glucose contents. In addition, alpha-Proteobacteria and Clostridia phyla were abundant in BN-specific bacterial microbiota at panicle initiation. These results suggest that the increased N fixation in BN at panicle initiation might be sustained both by the non-structural carbohydrate supply from photosynthetic apparatus and BN-specific bacterial microbiota including diazotrophs.

Cytological diagnosis of pleural mesothelioma (PM) is controversial even using ancillary markers (BAP1, MTAP and CDKN2A). Here, we aimed to prospectively validate a previously developed 117-gene expression panel for the differential cytological diagnosis of epithelioid, biphasic PM and mesothelial hyperplasia. Seventy-seven pleural effusions were classified using the 117-gene expression levels (NanoString system). Sixty-eight cases were also screened for ancillary markers. The performance of both gene panel and ancillary markers was evaluated using ROC metrics. A score using the top consistently deregulated genes between epithelioid and biphasic PM was built to subtype malignant effusions. The panel alone reached a diagnostic accuracy (0.89) comparable to the best marker combination (BAP1 plus MTAP: 0.88). Ancillary tests missed 8 PMs, seven of which were correctly classified by the panel. The score built by averaging the expression levels of MSLN, CLDN15 and CFB showed an accuracy of 0.80 in subtyping epithelioid and biphasic effusions. The 117-gene panel is effective for PM cytological diagnosis of epithelioid and biphasic PM. This tool can be complementary to ancillary markers, reducing invasive procedures and allowing an earlier diagnosis. Finally, the possibility to subtype PM on effusions strengthens the panel role in PM diagnosis and management.

Hexabromocyclododecane (HBCD) was most important flame retardant in Expanded Polystyrene foam and Extruded Polystyrene foam in the past forty years in the world. China was the major producer and user of HBCD, and the total HBCD production was about 0.3 million tons. Although HBCD has been completely banned in China in 2021 because of its long-range transport, bioaccumulation and toxicity, there's still a lot of residues in environment. Therefore, we reviewed multiple studies concerning the distribution of HBCD in diverse environmental matrices, such as air, dust, soil, water, sediment and biota. Results revealed that HBCD levels in different environments in China present a geographical variation and were at high level compared with other countries. In all environmental media, relatively high HBCD concentrations have been found in industrial and urban areas. Industrialization and urbanization are two important factors that influence the concentration and distribution of HBCD in the environment. In terms of isomer, γ-HBCD was the dominant isomer in soil, water, and sediment, while in the biota, α-HBCD was the predominant isomer.

To date, zinc ion batteries (ZIBs) have been attracting extensive attention due to their outstanding properties and the potential to be the solution for next-generation energy storage systems. However, the uncontrollable growth of zinc dendrites and water-splitting issues seriously restrict the further scalable application. Over the past few years, solid polymer electrolytes (SPEs) have been regarded as a promising alternative to address these challenges and facilitate the practical advancement of zinc batteries. In this review, we revisited the research progress of SPEs applied in zinc batteries in the past few years and focus on introducing cutting-edge polymer science and technologies that can be utilized to prepare advanced SPEs for high-performance zinc batteries. The operating mechanism of SPEs and the functions of polymers will be summarized. To highlight the polymer functions, SPEs are categorized into three types, respectively, homogenous polymer SPEs, hybrids polymer SPEs, and nanocomposites SPEs, which are expected to reveal the roles and principles of various polymers in zinc batteries. This review presents the current research progress and fundamental mechanisms of polymer-based SPEs in zinc batteries, outlines the challenging issues encountered, and meanwhile proposes potential solutions for future endeavours.

Objective: The study aimed to evaluate the effects of monoclonal antibodies (mAbs) acting on the calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP/R mAbs) on comorbid symptoms of depression, anxiety, and fatigue in migraine patients resistant to traditional prophylaxis. Methods: The study was an open-label prospective study assessing comorbidities in patients with high frequency (HFEM) and chronic migraine (CM), medication overuse headache (MOH), and resistance to traditional prophylaxis treated with anti-CGRP/R mAbs for 3 months. Results: 77 patients were enrolled with either HFEM (21%) or CM (79%) with or without MOH (56% and 44% respectively). We identified 21 non-responders (27%) and 56 responders (73%), defined on the reduction ≥ 50% of headache frequency. The two groups were highly homogeneous for investigated comorbidities. Disease severity in terms of headache frequency, migraine-related disability, and affective comorbid symptoms were reduced in both groups with different thresholds; allodynia and fatigue were ameliorated only in responders. Conclusion: anti-CGRP/R antibodies improve pain together with affection, fatigue, and sensory sensitization in migraine patients.

The human T-cell leukemia virus type 1 (HTLV-1) is the only known human oncogenic retrovirus. HTLV-1 can cause a cancer called adult T-cell leukemia/lymphoma (ATL). The virus is transmitted through body fluids of infected individuals, primarily breast milk, blood, and semen. At least 5–10 million people in the world are infected with HTLV-1. In addition to ATL, HTLV-1 infection can also cause HTLV-I-associated myelopathy (HAM /TSP). ATL is characterized by low viral ex-pression and poor prognosis. The oncogenesis triggered by HTLV-1 is extremely complex and the molecular mechanisms are not fully understood. However, viral regulatory proteins Tax and HTLV-1 bZIP factor (HBZ) have been shown to play key roles in the transformation of HTLV-1-infected T cells. Moreover, several studies have shown that the final fate of HTLV-1-infected transformed T cell clones is the result of a complex interplay of HTLV-1 oncogenic protein expression with cellular transcription factors that subvert the cell cycle and disrupt reg-ulated cell death, thereby exerting their transforming effects. This review provides updated in-formation on the mechanisms underlying the transforming action of HTLV-1 and the potential therapeutic targets to combat ATL.

Impact in the form of innovation and commercialisation is an essential component of publicly funded research projects. PHUSICOS, an H2020 Innovation Action project, aims at demonstrating the use of nature-based solutions for mitigating hydrometeorological hazards in rural and mountainous areas. The work program is built around key innovation actions, and each WP leader specifically responsible for nurturing innovation processes, maintaining market focus and ensuring relevance for the intended recipients of the project results. Key success criteria for PHUSICOS include up-scaling and mainstreaming of NBS to reach broader market access. An innovation strategy and supporting tools for implementing this within PHUSICS has been developed and key concepts forming the basis for this strategy are presented in this research note.

Hang-ju was one of five officinal varieties of Flos chrysanthemum for its edible and potable usage. Besides Flos Chrysanthemum (FL), there were also Bud Chrysanthemum (BC) and Fetal Chrysanthemum (FC) at the early and late stage of buds, respectively, in the consumption market of Hang-ju with higher prices. Whether the quality and efficiency of BC and FC was superior to FL or merely consumption misunderstandings? Three commercial products of Hongxinju, a representive cultivar of Hang-ju were studied with a GC-MS based metabolomics approach, complemented with morphology, contents of moisture and protein and the anti-oxidant activity, to reveal the metabolic alterations of violate components in Hongxinju in different flowering stage and at different processing periods. It revealed that most of the violate components were increased from fresh FC to FL, and the low-boiling fractions, inflammatory methyl arachidonate and air-polluting component of ethylbenzene were declined while the representative components with pungent flavor and cool nature of a-curcumene and (Z,Z,Z)-9,12,15-octadecatrienoic acid, vision improving carotenol of rhodopin and high-boiling fractions were elevated after processed in final FL compared with that in BC and/or FC. Though the content of protein and anti-oxidative capacity of final BC and FC were nearly equal to those of FL, in comprehensive consideration of the representative components related with the efficiency in heat cooling and vision improving, as well as the representative components related with inflammation and air-pollution, final FL was recommended other than BC and FC in the practice of medicine with the yield and quality integrated into account.

The decompensation trajectory check is a basic step to assess the clinical course and to plan future therapy in hospitalized patients with acute heart failure (ADHF). Due to the atypical presentation and clinical complexity, trajectory checks can be challenging in the oldest old patients with acute HF. Point of care ultrasound (POCUS) proved to be helpful in the clinical decision-making of patients with dyspnea, but no study has attempted to verify its effectiveness in predicting determinants of HF in-hospital worsening. In this single-center prospective study, we consecutively enrolled patients aged 75 or older hospitalized with acutely decompensated HF in a tertiary care hospital. All the patients underwent complete clinical examination, blood tests, and POCUS including Lung Ultrasound, Focused Cardiac Ultrasound, Pleural Effusion score (PEFs), and Inferior Vena Cava (IVC) assessment. Out of 184 patients hospitalized with ADHF enrolled in the study, sixty experienced HF in-hospital worsening. No differences were found among patients with HF worsening and controls in terms of age, gender, frailty, and left ventricular ejection fraction. By multivariable logistic analysis, total PEFs [aOR: 1.15 (CI95% 1.02– 1.33), p = 0.043], and IVC collapsibility [aOR: 0.90 (CI95% 0.83 – 0.95), p = 0.039] emerged as independent predictors of acute HF worsening after extensive adjustment for potential confounders.

The fertility rate and litter size of female pigs are critically affected by the expression of estrus. The objective of this study was to elucidate the regulatory mechanisms of estrus expression by analyzing the differential expression of genes and long intergenic non-coding RNAs (lincRNA), as well as the utilization of alternative polyadenylation (APA) sites, in the vulva and vagina during the estrus and diestrus stages of Large White and indigenous Chinese Mi gilts. Our study revealed that the number of differentially expressed genes (DEG) in the vulva was less than that in the vagina, and the DEGs in the vulva were enriched in pathways such as “neural” pathways and steroid hormone responses, including the “Calcium signaling pathway” and “Oxytocin signaling pathway”. The DEGs in the vagina were enriched in the “Metabolic pathways” and “VEGF signaling pathway”. Furthermore, 27 and 21 differentially expressed lincRNAs (DEL), whose target genes were enriched in the “Endocrine resistance” pathway, were identified in the vulva and vagina, respectively. Additionally, we observed that 63 and 618 transcripts of the 3'-untranslated region (3'-UTR) were lengthened during estrus in the vulva and vagina, respectively. Interestingly, the genes undergoing APA events in the vulva exhibited species-specific enrichment in neural or steroid-related pathways, whereas those in the vagina were enriched in apoptosis or autophagy-related pathways. Further bioinformatic analysis of these lengthened 3'-UTRs revealed the presence of multiple miRNAs binding sites and cytoplasmic polyadenylation element (CPE) regulatory elements. In particular, we identified more than 10 CPEs in the validated lengthened 3'-UTRs of the NFIX, PCNX4, CEP162 and ABHD2 genes using RT-qPCR. These findings demonstrated the involvement of APA and lincRNAs in the regulation of estrus expression in female pigs, providing new insights into the molecular mechanisms underlying estrus expression in pigs.

Different bone bruise patterns observed on magnetic resonance imaging (MRI) after non-contact anterior cruciate ligament (ACL) rupture and lateral patellar dislocation may indicate different injury mechanism of knee. In order to investigate the typical bone bruising patterns after ACL rupture and patellar dislocation. In this study, 77 ACL rupture and 77 patellar dislocation patients’ knee MR images with bone bruises between August 2020 and March 2022at our institution were selected and analyzed, respectively. Sagittal and transverse planes images were used to determine the bone bruise location in the lateral-medial and superior-inferior directions of the MR images. The presence, location, and intensity of the bone bruises within specific compartments of the femur and tibial after ACL rupture and patellar dislocation were recorded. Relative bone bruise patterns of the ACL rupture and patellar dislocation were classified and analyzed. Results showed that there were 4 kinds of bone bruise (1-,2-,3-,4- bone bruises) patterns after ACL rupture. The most common two patterns after ACL rupture were 3- bone bruises (including lateral side of femur and both lateral and medial side of tibia, LF+BT; both lateral and medial side of femur and lateral side of tibia, BF+LT, medial side of femur and both lateral and medial side of tibia, MF+BT) followed by 4- bone bruises (both lateral and medial side of femur and tibia, BF+BT), 2- bone bruises (LF+LT, lateral side of femur and tibia; MF+LT, medial side of femur and lateral side of tibia; LF+MT, lateral side of femur and medial side of tibia; MF+MT, medial side of femur and tibia; 0+BT, both lateral and medial side of tibia;), and 1- bone bruise (0+LT, only lateral side of tibia). There was only 1 pattern bone bruise (latera femur and medial patella bone bruise) of patellar dislocation, the most common pattern of patellar dislocation was in the inferior medial patella and lateral anterior inferior femur. The results suggest that the pattern of bone bruise after ACL rupture and patellar dislocation is completely different. There were 4 kinds of bone bruise patterns after non-contact ACL rupture while there was only 1 kind of bone bruise pattern after patellar dislocation bone bruise patients which was in the inferior medial patella and lateral anterior inferior femur.

Nature Based Solutions (NBS) are becoming increasingly important in both the EU and individual countries' political agendas, as a sustainable means to reduce the risk posed by hydrometeorological hazards. However, as the use of NBS is increasing, a number of barriers regarding their practical implementation also becomes apparent. A number of review studies have summarized and classified barriers, mainly in urban settings. PHUSICOS is a H2020 Innovation Action to demonstrate the use of NBS in rural and mountain landscapes. Large scale demonstrator case sites with several sub-projects are established in Italy, Norway and in the French and Spanish Pyrenees. The present paper describes the project's NBS measures, and their experienced barriers, some of which have resulted in full cancellation of the planned interventions. Many of the barriers experienced in rural settings have the same root causes as the ones described from urban areas, and the main barrier-creating mechanisms are institutional factors, resistance among stakeholders and technical and economic issues. The key element, however, is lack of knowledge about the ability of NBS to deliver a series of co-benefits in addition to their risk-reducing effects, and that long-term thinking is required to see the effect of many of these co-benefits.

Health care is currently showing a fall in heart failure (HF) prevalence and incidence particularly in developed countries, but with only a subset receiving appropriate therapy to protect the heart against maladaptive processes such as fibrosis and hypertrophy. Appropriate markers of advanced HF are still needed, which should help choosing the most suitable therapy and avoid major compliance problems. Speckle tracking echocardiography (STE) is a good choice, being a non-invasive imaging technique and is able to assess cardiac deformation in a variety of conditions. Several multicenter studies and meta-analyses have demonstrated its clinical applications and accuracy in early and late stages of HF, as well as its association with both left ventricular (LV) filling pressures and myocardial oxygen consumption, the two are important parameters in the evaluation of HF patients. Also, STE assists in assessing right ventricular free-wall longitudinal strain (RVFWLS) which is a solid predictor of right ventricle failure (RVF) following LV assist device (LVAD) implantation. Despite its limitations, STE plays an essential role in the clinical evaluation of patients with HF, early and advanced, in explaining symptoms and signs and also as an accurate prognosticator. The aim of this review is to examine the advantages of STE in early evaluation of myocardial dysfunction and their correlation with right heart catheterization (RHC) parameters, which should have a significant clinical relevance in the management of HF patients.

The mRNA vaccines for SARS-CoV-2 have demonstrated efficacy and immunogenicity in the re-al-world setting. However, most of the research on vaccine immunogenicity has been centered on characterizing the antibody response, with limited exploration into the persistence of spike-specific memory B cell response. Here we monitored the durability of the memory B cell response and characterize the trajectory of spike-specific B cell phenotypes in healthy individuals who have received two doses of the BNT162b2 vaccine up to 9 months post-vaccination. To profile the spike-specific B cell response we applied the tSNE and Cytotree automated approaches. Our data showed the induction of spike-specific IgA+ and IgG+ plasmablasts and IgA+ activated cells 7 days after the second dose which disappeared 3 months later, while subsets of spike-specific IgG+ resting memory B cells became predominant 9 months after vaccination, and they were capable to differentiate into spike-specific IgG secreting cells when in vitro restimulated. Other subsets of spike-specific B cells, such as IgM+ or unswitched IgM+IgD+ or IgG+ double negative/atypical cells, were also elicited by the BNT162b2 vaccine and persisted up to month 9. The analysis of circulating spike-specific IgG, IgA and IgM was in line with the plasmablasts observed. The longitudinal analysis of the antigen-specific B cell response elicited by mRNA-based vaccines provides valuable insights into our understanding of the immunogenicity of this novel vaccine platform destined to a future widespread use, and it is crucial in guiding future decisions and vaccination schedules.

The Diaphorina citri Kuwayama (D. citri) is one of the major pests in the citrus industry, which spreads Citrus Huanglongbing disease. It has developed resistance to chemical insecticides. Therefore, searching for greener solutions for pest management is critically important. The main aim of this study was to evaluate the repellent and insecticidal efficacy of essential oils (EOs) from four species of Myrtaceae plants: Psidium guajava (PG), Eucalyptus robusta (ER), Eucalyptus tereticornis (ET), and Baeckea frutescens (BF) against D. citri and to analyze their chemical composition. GC-MS analysis was performed, and the results indicated that the EOs of PG, ER, ET, and BF were rich in terpenoids, ketones, esters, and alcohol compounds. The repellent rate of all four EOs showed that it decreased with exposure time but increased with concentrations of EOs. Repellent rates ranged from 80.50% to 100.00% after treating D. citri for 6 hours with four EOs at 100% concentration and decreased to 67.71% to 85.49% after 24 hours of exposure. Among the compounds from the EOs tested, eucalyptol had the strongest repellent activity, with a 24-hour repellency rate of 100%. The contact toxicity bioassay results showed that all EOs have insecticidal toxicity to D. citri; the LC50 for nymphs was 36.47-93.15 mL/L, and for adults, it was 60.72-111.00 mL/L. These results show that when PG is used as the reference material, both ER, ET, and BF EOs have strong biological activity against D. citri, which provides a scientific basis for the further development of plant-derived agrochemicals.

The ITALUNG trial started in 2004 and compared lung cancer (LC) and other-causes mortality in 55-69 years-aged smokers and ex-smokers who were randomized to four annual chest low-dose CT (LDCT) or usual care. ITALUNG showed a lower LC and cardiovascular mortality in the screened subjects after 13 years of follow-up, especially in women, and produced many ancillary studies. They included recruitment results of a population-based mimicking approach, development of software for computer aided diagnosis (CAD) and lung nodules volumetry, LDCT assessment of pulmonary emphysema and coronary artery calcifications (CAC) and their relevance to long-term mortality, results of a smoking-cessation intervention, assessment of the radiations dose associated with screening LDCT, and the results of biomarkers assays. Moreover ITALUNG data indicated that screen-detected LCs are mostly already present at baseline LDCT, can present as Lung Cancer associated with Cystic Airspaces, and can be multiple. However, several issues of LC screening are still unaddressed. They include the annual vs biennial pace of LDCT, choice between opportunistic or population-based recruitment and between uni or multi-center screening, implementation of CAD-assisted reading, containment of false positive and negative LDCT results, incorporation of emphysema and CAC quantification in models of personalized LC and mortality risk, validation of ultra-LDCT acquisitions, optimization of the smoking-cessation intervention and prospective validation of the biomarkers.

Despite the recognized potential of nanoparticles, only a few formulations have progressed to clinical trials, and an even smaller number have been approved by the regulatory authorities and marketed. Virus-like particles (VLPs) have emerged as promising alternatives to most explored nanoparticles because of the absence of viral genetic material, their incapacity to replicate, mimicry of viral structure, and tropism conservation. Furthermore, VLPs can be surface functionalized with small molecules to improve circulation half-life and target specificity. Through the functionalization and coating of VLPs, it is possible to optimize the response properties to a given stimulus, such as heat, pH, an alternating magnetic field, or even enzymes. Surface functionalization can also modulate other properties, such as biocompatibility, stability, and specificity, deeming VLPs as potential vaccine candidates or delivery systems. In this review, we address the different types of functionalization of VLPs, their importance, and their consequent biomedical applications.

Abstract: Lipodystrophies (LDs) are rare, complex disorders of the adipose tissue characterized by selective fat loss, altered adipokines profile and metabolic impairment. Sirtuins (SIRTs) are class III NAD+-dependent histone-deacetylases linked to fat metabolism. SIRT1 plays a critical role in metabolic health by deacetylating target proteins in tissues including liver, muscle and adipose tissue. Circulating SIRT1 levels have been found to be reduced in obesity while increased in anorexia nervosa and in patients experiencing weight loss. We evaluated circulating SIRT1 levels in relation to fat amount in 32 lipodystrophic patients affected by congenital or acquired LDs compared to non-LD subjects (24 with anorexia nervosa, 22 normal weight and 24 with obe-sity). SIRT1 serum levels were higher in LDs as compared with normal weight subjects (mean ± SEM: 4.17 ± 0.48 vs. 2.59 ± 0.20 ng/mL) or subjects with obesity (1.7 ± 0.39 ng/mL), whereas they were close to those measured in anorexia nervosa (3.44 ± 0.46 ng/mL). Our findings show that within the LD group there was no relationship between SIRT1 levels and the amount of body fat. The mechanisms responsible for secretion and regulation of SIRT1 in LD deserve further investi-gation.

An influenza A virus (H3N2) with an envelope with the same structure as COVID-19 was used for antiviral testing of material surfaces, in comparison with some results of feline calicivirus. The evaluation method used was the film adhesion method, in which the virus solution is placed on the material and adhered to it using a film. The evaluation method was based on the film adhesion method, in which the virus solution is placed on the material and adhered with a film, and the plaque method, in which the cell virus is allowed to infect the material and form plaques, but the appropriate virus concentration must be adjusted to observe the plaques. When not under that restriction, the plaques are often incomplete; this is observed. For this reason, this study applied an area measurement method that can reflect viral activity even when plaques are not obtained. This study revealed that different types of metallic materials have different antiviral properties. Specifically, the antiviral activity of iron, carbon steel, and nickel was relatively high, while that of stainless steel and titanium was relatively low. The order of antiviral activity was as follows: Fe, SS400, Ni, SUS316L, SUS304, and Ti.

Based on a wealth of evidence, aspirin is one of the cornerstones of secondary prevention of cardiovascular disease. However, despite several studies showing efficacy also in primary prevention, an unopposed excess risk of bleeding leading to a very thin safety margin is evident in subjects without a clear acute cardiovascular event. Overall, the variability in recommendations from different scientific societies for aspirin use in primary prevention is a classic example of failure of simple risk stratification models based on competing risks (atherothrombosis vs. bleeding), perceived to be opposed but intertwined at the pathophysiological level. Notably, cardiovascular risk is dynamic in nature and cannot be accurately captured by scores, which do not always consider risk enhancers. Furthermore, the widespread use of other potent medications in primary prevention, such as lipid-lowering and anti-hypertensive drugs, might have reduced the benefit of aspirin in recent trials. Some authors, drawing from specific pathophysiological data, have suggested that specific subgroups might benefit more from aspirin. This includes patient with diabetes and those with obesity, as well as considering sex-based differences. Moreover, molecular analysis of platelet reactivity has been proposed. A beneficial effect of aspirin has also been demonstrated for the prevention of cancer, especially colorectal. This review explores evidence and controversies concerning the use of aspirin in primary prevention, considering new perspectives in order to develop a personalized approach.