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Nowadays, the scientific community has focused on dealing with different kinds of diseases by exploring the chemistry of various heterocycles as novel drugs. In this connection, medicinal chemists identified carbonic anhydrases (CA) as one of the biologically active targets for curing various diseases. The widespread distribution of these enzymes and the high degree of homology shared by the different isoforms offer substantial challenges to discovering potential drugs. Medicinal and synthetic organic chemists have been continuously involved in developing CA inhibitors. This review explored the chemistry of different heterocycles as CA inhibitors using the last 11 years of published research work. It provides a pathway for young researchers to further explore the chemistry of a variety of synthetic as well as natural heterocycles as CA inhibitors., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Background: Aging of the male prostate is an inevitable process in which the prostate undergoes hyperplasia, and this growth may lead to compression of the urethra, resulting in voiding dysfunction and associated symptoms, and an increased risk of prostate cancer. Despite the significance of prostate aging, the molecular mechanisms involved are still not fully understood. Methods: Prostate split by lobes from young (2 months) and aged (24 months) mice were collected for single-cell RNA sequencing (scRNA-seq) analysis. Tissues from both anterior prostate (AP) and ventral/dorsal/lateral prostate (VDLP) were included in the study. Data analysis included unsupervised clustering using the uniform manifold approximation and projection (UMAP) algorithm to identify distinct cell types based on marker gene expression. Differential gene expression analysis was performed to identify age-related changes in gene expression across different cell types. Functional enrichment analysis was conducted to elucidate biological pathways associated with differentially expressed genes. Additionally, cellular interactions and developmental trajectories were analyzed to characterize cellular dynamics during prostate aging. Results: The single-cell transcriptome analysis of the mouse prostate during aging revealed heterogeneity across various cell types and their changes during the aging process. We found a significant increase in the proportion of mesenchymal and immune cells in aged mice. Our study unveiled alterations in genes and pathways associated with cellular senescence, oxidative stress, and regeneration in epithelial cells. Furthermore, we observed that basal cells may undergo epithelial-mesenchymal transition (EMT) to become mesenchymal cells, particularly prominent in aged mice. Additionally, immune cells, notably macrophages and T cells, exhibited a heightened inflammatory response in aged mice. Conclusion: In summary, our study provides a comparative analysis of the single-cell transcriptome of the aged and young mice prostates, elucidating cellular and molecular changes between the aged and young mice prostates. [ABSTRACT FROM AUTHOR]

Background The rationale of the study was to analyze the impact of age on quality of life (QoL) in patients who had undergone cardiac surgery with consecutive extracorporeal life support (ECLS) treatment. Methods The study population consisted of 200 patients, operated upon between August 2006 and December 2018. The patient cohort was divided into two groups following an arbitrary cutoff age of 70 years. Comparative outcome analysis was calculated utilizing the European Quality of Life-5-Dimensions-5-Level Version (EQ-5D-5L). Results A total of 113 patients were 70 years or less old (group young), whereas 87 patients were older than 70 years (group old). In 45.7% of cases, the ECLS system was established during cardiogenic shock and external cardiac massage. The overall survival-to-discharge was 31.5% (n = 63), with a significantly better survival in the younger patient group (young = 38.9%; old = 21.8%, p = 0.01). Forty-two patients (66%) responded to the QoL survey after a median follow-up of 4.3 years. Older patients reported more problems with mobility (y = 52%; o = 88%, p = 0.02) and self-care (y = 24%; o = 76%, p = 0.01). However, the patients' self-rated health status utilizing the Visual Analogue Scale revealed no differences (y = 70% [50–80%]; o = 70% [60–80%], p = 0.38). Likewise, the comparison with an age-adjusted German reference population revealed similar QoL indices. There were no statistically significant differences in the EQ-5D-5L index values related to sex, number of comorbidities, and emergency procedures. Conclusion Despite the limited sample size due to the high mortality rate especially in elderly, the present study suggests that QoL of elderly patients surviving ECLS treatment is almost comparable to younger patients. [ABSTRACT FROM AUTHOR]

This paper presents the first functional encryption (FE) scheme for the attribute-weighted sum functionality that supports the uniform model of computation. In such an FE scheme, encryption takes as input a pair of attributes (x, z) where x is public and z is private. A secret key corresponds to some weight function f, and decryption recovers the weighted sum f(x)z. In our scheme, both the public and private attributes can be of arbitrary polynomial lengths that are not fixed at system setup. The weight functions are modelled as Logspace Turing machines . Prior schemes could only support non-uniform Logspace. The proposed scheme is proven adaptively simulation secure under the well-studied symmetric external Diffie–Hellman assumption against an arbitrary polynomial number of secret key queries both before and after the challenge ciphertext. This is the best possible security notion that could be achieved for FE. On the technical side, our contributions lie in extending the techniques of Lin and Luo [EUROCRYPT 2020] devised for indistinguishability-based payload hiding attribute-based encryption for uniform Logspace access policies and the "three-slot reduction" technique for simulation-secure attribute-hiding FE for non-uniform Logspace devised by Datta and Pal [ASIACRYPT 2021] to the context of simulation-secure attribute-hiding FE for uniform Logspace. [ABSTRACT FROM AUTHOR]

Objective: Increased frequency of autoimmune thyroid disease, particularly Hashimoto's thyroiditis (HT) was reported several studies in the literature, in individuals with childhood-onset systemic lupus erythematosus (cSLE). Our study aimed to investigate the prevalence and contributing factors of thyroid dysfunction and HT among cSLE patients. Methods: Thyroid function tests were obtained cross-sectionally from cSLE patients. Demographic, clinical, and laboratory characteristics and activity scores were collected from medical records. Patients diagnosed with cSLE were compared to the healthy control group for the frequency of thyroid dysfunction. The Mann-Whitney U, independent samples t test, and the Chi-square or Fisher's exact test were used to compare study groups. A p -value below 0.05 was considered statistically significant. Results: Out of 73 cSLE patients, 14 (19.1%) had subclinical hypothyroidism, 9 (12.3%) had clinical hypothyroidism, 12 (16.4%) were diagnosed with HT, and 12 (16.4%) had a family history of HT. Thyroid USG was performed in 5 euthyroid patients and 1 borderline subclinical hypothyroid patient with positive thyroid autoantibody and reported as diffuse heterogeneous echogenicity enlargement in the thyroid gland. There were no significant differences in clinical and laboratory data or medication used between the groups with and without HT; however, patients with HT had a higher frequency of clinical hypothyroidism and family history of HT. Cumulative prednisolone dose was significantly lower in patients diagnosed with HT. The frequency of HT was considerably higher in patients with cSLE compared to the healthy control group. Conclusion: The results demonstrate an increased incidence of HT in cSLE patients, even if they are euthyroid, and recommend that cSLE patients be screened more frequently. [ABSTRACT FROM AUTHOR]

Background. Emerging research has identified ferroptosis as a novel form of programmed cell death, and Arachidonic acid 15-lipoxygenase-1 (ALOX15) stands out as a pivotal gene in mediating this process. Nonetheless, the role of ALOX15 in human tumors remains elusive. Methods. We utilized TIMER 2.0 to investigate the differential expression profiles of ALOX15 between pan-cancer and normal tissues. Further data from the TCGA, GEPIA, UALCAN, HPA, and CPTAC databases were analyzed to verify the levels of mRNA, protein expression, and promoter methylation across various cancer types. The survival prognosis, clinical features, and genetic alterations of ALOX15 were also evaluated. GO/KEGG enrichment analyses and single-cell transcriptome sequencing were employed for functional enrichment analysis. The gene mutation of ALOX15 and its prognostic value were analyzed using the cBioPortal platform. Finally, the relationship between ALOX15 and immune cell infiltration, Immune Checkpoints (ICKs), genomic instability, and drug sensitivity was further explored using GSCA. Results. Our findings revealed that the transcription and protein expression of ALOX15 were significantly reduced in HNSC, LUAD, LUSC, SKCM, KICH, and THCA, while they were up-regulated in ESCA, LIHC, PRAD, and UCEC. Notably, the expression of ALOX15 had prognostic value for certain cancers, including LUAD, LUSC, LIHC, KIRC, HNSC, THCA, and LGG. Additionally, ALOX15 expression was markedly correlated with clinical characteristics, immune cell infiltration, ICKs, genomic instability, and antitumor drug sensitivity in various tumors. Gene mutations of ALOX15 and their prognostic value were discovered in pan-cancers. Furthermore, GO/KEGG analysis and single-cell transcriptome sequencing indicated that ALOX15 was significantly associated with cancer-related pathways. Conclusion. Our comprehensive pan-cancer analysis shed light on the role and significance of ALOX15, suggesting its potential as a prognostic and immunotherapeutic marker for pan-cancer. These findings may provide new directions and evidence for cancer therapeutics. [ABSTRACT FROM AUTHOR]

Objective: Numerous observational and retrospective studies have demonstrated an association between Autoimmune Thyroiditis (AIT) and various systemic Autoimmune Diseases (AIDs). However, the causal relationship between them remains uncertain. This study aims to investigate the causal link between AIT and diverse types of AIDs utilizing the Mendelian Randomization (MR) method. Method: We assessed the causal relationship between AIT and eight prevalent AIDs. Summary statistics from genome-wide association studies (GWAS) were sourced from the FinnGen biobank and IEU Open GWAS database. Two-sample MR analyses were conducted, with the primary statistical approach being the Inverse Variance Weighting (IVW) method. This was complemented by a series of sensitivity analyses, and the robustness of the findings was evaluated through the estimation of heterogeneity and pleiotropy. Results: When AIT was considered as the outcome, MR evidence suggested an association between Rheumatoid arthritis (RA), Type 1 diabetes (T1D), and Systemic lupus erythematosus (SLE) with AIT. Utilizing the Inverse Variance Weighting (IVW) method, we observed an increased risk of AIT with exposure to RA (P = 0.024, OR=1.25; 95% CI = 1.03,1.52), T1D (P < 0.001, OR=1.27 95% CI = 1.11,1.46), and SLE (P = 0.037, OR=1.14; 95% CI = 1.04,1.26). Conversely, no significant genetic causal relationship with AIT was found for Sjogren's syndrome (SS), Ankylosing Spondylitis (AS), Multiple sclerosis (MS), Crohn's disease (CD), and Ulcerative colitis (UC). Conclusion: This study identified RA, T1D, and SLE as triggering factors for AIT. The incidence rate of AIT in patients with RA, T1D, and SLE may be higher than that in the general population. Therefore, individuals with these three diseases should undergo regular monitoring of thyroid-related indicators. [ABSTRACT FROM AUTHOR]

Purposes: To provide novel aspects for the preoperative diagnosis and appropriate differentiation strategies for follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA). Methods: Among 25,765 cases, a total of 326 patients with follicular thyroid neoplasms between 2013 and 2019 were enrolled. Patient demographics, perioperative parameters, surgical profiles and oncologic outcomes were collected and analyzed. Results: There were no significant differences in preoperative ultrasound findings between FTA and FTC patients. The true positive rate (sensitivity) and true negative rate (specificity) of fine needle aspiration (FNA) for FTA patients were 0.6956 and 0.5000, respectively, and those for FTC patients were 0.0714 and 0.9348, respectively. Patients with FTC presented significantly higher serum thyroglobulin (TG) levels than patients with FTA. Preoperative TG level was positively related to tumor invasiveness and recurrence or distant metastases in FTC patients. There were 55 patients with Hashimoto's thyroiditis (HT), accounting for 16.87% of enrolled patients. HT patients had significantly lower serum TG concentrations than antibody-negative patients. Among HT patients, no significant differences were observed in TG levels between the FTA and FTC groups. Instead, FTA patients had significantly higher serum thyroid stimulating hormone (TSH) levels and lower serum T3 (Triiodothyronine) levels compared to FTC patients. Serum TSH level >1.736U/L was associated with benign follicular neoplasms in HT patients according to the receiver operating characteristic (ROC) curve. Conclusion: Distinguishing FTC from FTA remains a challenge for ultrasonography and FNA. Serum TG should be measured as a risk factor of FTC. However, in HT patients, serum TSH levels can serve as a more reliable indicator for differentiating FTC from FTA preoperatively. [ABSTRACT FROM AUTHOR]

During the process of muscle regeneration post‐injury in adults, muscle stem cells (MuSCs) function is facilitated by neighboring cells within the pro‐regenerative niche. However, the precise mechanism triggering the initiation of signaling in the pro‐regenerative niche remains unknown. Using single‐cell RNA sequencing, 14 different muscle cells are comprehensively mapped during the initial stage following injury. Among these, macrophages and fibro‐adipogenic progenitor cells (FAPs) exhibit the most pronounced intercellular communication with other cells. In the FAP subclusters, the study identifies an activated FAP phenotype that secretes chemokines, such as CXCL1, CXCL5, CCL2, and CCL7, to recruit macrophages after injury. Il1rl1, encoding the protein of the interleukin‐33 (IL‐33) receptor, is identified as a highly expressed signature surface marker of the FAP phenotype. Following muscle injury, autocrine IL‐33, an alarmin, has been observed to activate quiescent FAPs toward this inflammatory phenotype through the IL1RL1‐MAPK/NF‐κB signaling pathway. Il1rl1 deficiency results in decreased chemokine expression and recruitment of macrophages, accompanied by impaired muscle regeneration. These findings elucidate a novel mechanism involving the IL‐33/IL1RL1 signaling pathway in promoting the activation of FAPs and facilitating muscle regeneration, which can aid the development of therapeutic strategies for muscle‐related disorders and injuries. [ABSTRACT FROM AUTHOR]

In this study, we carried out an independent validation of two methane retrieval algorithms using spectra from the Infrared Atmospheric Sounding Interferometer (IASI) that has been aboard the Meteorological Operational Satellite A (MetOp-A) since 2006. Both algorithms, one developed by the Laboratoire de Météorologie Dynamique (LMD), called the non-linear inference scheme (NLISv8.3), and the other by the Rutherford Appleton Laboratory (RAL), referred to as RALv2.0, provide long-term global CH4 concentrations using distinctively different retrieval approaches (neural network vs. optimal estimation, respectively). They also differ with respect to the vertical range covered, where LMD provides mid-tropospheric dry-air mole fractions (mt CH4), and RAL provides mixing ratio profiles from which we can derive total column-averaged dry-air mole fractions (X CH4) and potentially two partial column layers (q CH4). We compared both CH4 products using the Copernicus Atmospheric Monitoring Service (CAMS) model, in situ profiles (range extended using CAMS model data), and ground-based Fourier transform infrared (FTIR) remote-sensing measurements. The average difference (in mt CH4) with respect to in situ profiles for LMD ranges between -0.3 and 10.9 ppb, while for RAL the X CH4 difference ranges between -4.6 and -1.6 ppb. The standard deviation (SD) of the observed differences between in situ measurements and RAL retrievals is 14.1–21.9 ppb, which is consistently smaller than that between LMD retrievals and in situ measurements (15.2–30.6 ppb). By comparing with ground-based FTIR sites, the mean differences are within ±10 ppb for both RAL and LMD retrievals. However, the SD of the differences at the ground-based FTIR stations shows significantly lower values for RAL (11–15 ppb) than for LMD (about 25 ppb). The long-term trend and seasonal cycles of CH4 derived from the LMD and RAL products are further investigated and discussed. The seasonal variation in X CH4 derived from RAL is consistent with the seasonal variation observed by the ground-based FTIR measurements. However, the overall 2007–2015 X CH4 trend derived from RAL measurements is underestimated, if not adjusted, for an anomaly occurring on 16 May 2013 due to a L1 calibration change. For LMD, we see very good agreement at the (sub)tropics (<35 ° N– 35° S) but notice deviations in the seasonal cycle (both in the amplitude and phase) and an underestimation of the long-term trend with respect to the RAL and reference data at higher-latitude sites. [ABSTRACT FROM AUTHOR]

Autoimmune skin disorders, including Psoriasis, Lichen Planus, Vitiligo, Atopic Dermatitis, and Alopecia Areata, arise from a combination of genetic predisposition, external factors, and immunological dysfunction. It is well-documented that there is a strong correlation between autoimmune thyroid diseases and a range of dermatological disorders, especially urticaria. This review investigates possible links between autoimmune thyroiditis and a broader spectrum of autoimmune skin conditions, analyzing shared genetic markers, immunological mechanisms, and clinical correlations. Common pathogenic mechanisms include disrupted immune tolerance and oxidative stress, leading to chronic inflammation. Genetic factors, such as IL-23 receptor gene variants, increase the risk for Psoriasis, Alopecia Areata, and Hashimoto's thyroiditis. Additionally, CTLA-4 mutations enhance susceptibility to autoimmune thyroid and skin disorders. Shared genetic susceptibility was also reported in Lichen Planus and Vitilgo, even if different genetic loci might be involved. The breakdown of the immune system can determine a pro-inflammatory state, facilitating the development of autoimmunity and auto-antibody cross-reactions. The presence of similar antigens in skin cells and thyrocytes might explain why both tissues are affected. The significant overlap between these conditions emphasizes the necessity for a comprehensive diagnosis workup and treatment. Future research should focus on clarifying specific immunological pathways and identifying novel biomarkers. [ABSTRACT FROM AUTHOR]

In this paper, the effect of basalt fiber (BF) on the frost resistance of concrete under different curing conditions was investigated, and its frost resistance mechanism was analyzed. Three different curing conditions (normal curing, short-term curing, and seawater curing) were adopted, and concrete with different BF volume contents was designed. Freeze-thaw (FT) tests were carried out using the rapid freezing method to test the frost resistance of basalt fiber reinforced concrete (BFRC). Additionally, the mass loss rate (MLR), relative dynamic modulus of elasticity (RDME) change, and compressive strength reduction of specimens during the freeze-thaw cycles (FTCs) were evaluated. The results show that when the BF content is 0.15%, under normal curing, short-term curing, and seawater curing conditions, the residual compressive strength of BFRC after FTCs was increased by 5.4%, 28.1%, and 30.9%, respectively, compared to plain concrete. By incorporating BF into concrete, the development of microcracks can be effectively retarded, and damage generation during FTCs can be reduced. In addition, the microscopic morphological characteristics and pore structure characteristics of concrete further elucidate the frost resistance mechanism of BFRC from a microscopic perspective. [ABSTRACT FROM AUTHOR]

With the rapid development of satellite remote sensing technology, carbon-cycle research, as a key focus of global climate change, has also been widely developed in terms of carbon source/sink-research methods. The internationally recognized "top-down" approach, which is based on satellite observations, is an important means to verify greenhouse gas-emission inventories. This article reviews the principles, categories, and development of satellite detection payloads for greenhouse gases and introduces inversion algorithms and datasets for satellite remote sensing of XCO2. It emphasizes inversion methods based on machine learning and assimilation algorithms. Additionally, it presents the technology and achievements of carbon-assimilation systems used to estimate carbon fluxes. Finally, the article summarizes and prospects the future development of carbon-assimilation inversion to improve the accuracy of estimating and monitoring Earth's carbon-cycle processes. [ABSTRACT FROM AUTHOR]

In this study, we conducted a case-control investigation to assess the immunogenicity and effectiveness of primary and first booster homologous and heterologous COVID-19 vaccination regimens against infection and hospitalization, targeting variants circulating in Lebanon during 2021–2022. The study population comprised active Lebanese military personnel between February 2021 and September 2022. Vaccine effectiveness (VE) against laboratory-confirmed SARS-CoV-2 infection and associated hospitalization was retrospectively determined during different variant-predominant periods using a case-control study design. Vaccines developed by Sinopharm, Pfizer, and AstraZeneca as well as Sputnik V were analyzed. Prospective assessment of humoral immune response, which was measured based on the SARS-CoV-2 antispike receptor binding domain IgG titer, was performed post vaccination at various time points, focusing on Sinopharm and Pfizer vaccines. Statistical analyses were performed using IBM SPSS and GraphPad Prism. COVID-19 VE remained consistently high before the emergence of the Omicron variant, with lower estimates during the Delta wave than those during the Alpha wave for primary vaccination schemes. However, vaccines continued to offer significant protection against infection. VE estimates consistently decreased for the Omicron variant across post-vaccination timeframes and schemes. VE against hospitalization declined over time and was influenced by the variant. No breakthrough infections progressed to critical or fatal COVID-19. Immunogenicity analysis revealed that the homologous Pfizer regimen elicited a stronger humoral response than Sinopharm, while a heterologous Sinopharm/Pfizer regimen yielded comparable results to the Pfizer regimen. Over time, both Sinopharm's and Pfizer's primary vaccination schemes exhibited decreased humoral immunity titers, with Pfizer being a more effective booster than Sinopharm. This study, focusing on healthy young adults, provides insights into VE during different pandemic waves. Continuous research and monitoring are essential for understanding vaccine-mediated immune responses under evolving circumstances. [ABSTRACT FROM AUTHOR]

Background: Hybrid immunity provides better protection against COVID-19 than vaccination or prior natural infection alone. It induces high magnitude and broadly cross-reactive neutralising anti-Spike IgG antibodies. However, it is not clear how long these potent antibodies last, especially in the context of adenovirus-based COVID-19 vaccines. Methods: We conducted a longitudinal cohort study and enrolled 20 adults who had received an adenovirus-based COVID-19 vaccine before a laboratory-confirmed SARS-CoV-2 infection. We followed up the study participants for 390 days post the initial breakthrough infection. We assessed the longevity and cross-reactive breadth of serum antibodies against SARS-CoV-2 variants of concern (VOCs), including Omicron. Results: The binding anti-Spike IgG antibodies remained within the reported putative levels for at least 360 days and were cross-neutralising against Beta, Gamma, Delta, and Omicron. During the follow up period, a median of one SARS-CoV-2 re-infection event was observed across the cohort, but none resulted in severe COVID-19. Moreover, the re-exposure events were associated with augmented anti-Spike and anti-RBD IgG antibody titres. Conclusions: This study confirms that hybrid immunity provides durable broadly cross-reactive antibody immunity against SARS-CoV-2 variants of concern for at least a year (360 days), and that it is further augment by SARS-CoV-2 re-exposure. [ABSTRACT FROM AUTHOR]

Background: Hashimoto's thyroiditis (HT) is an inflammatory disease characterized by increased reactive oxygen species. Diets rich in anti-inflammatory and antioxidant properties may be linked to a reduced risk of developing HT. The aim of this study was to investigate the association between the dietary inflammatory index (DII) and dietary total antioxidant capacity (DTAC) with HT in Iranian adults. Methods: The study was a hospital-based case-control study conducted on 230 participants (115 cases and 115 controls). Dietary intake was assessed using a food frequency questionnaire (FFQ). The FFQ data were used to calculate DII and DTAC scores. Anthropometric measurements, thyroid function, and antibody tests were evaluated using standard methods. Multivariable logistic regression analysis was performed in both raw and adjusted models to determine the association between DII and DTAC scores with HT. Results: The average age of the participants was 39.76 ± 9.52 years. The mean body mass index in the case and control groups was 28.03 ± 6.32 and 26.43 ± 5.13 (kg/m2), respectively (P = 0.036). In the HT group, the DII level was higher (P < 0.001) and the DTAC level was lower than those in the healthy group (P = 0.047). In the multivariable logistic regression model, after adjusting for confounding factors, subjects in the last tertile of DII had a nonsignificantly higher HT risk than those in the first tertile (OR = 1.75; 95% CI = 0.83–3.65; P = 0.130). Regarding DTAC, the subjects in the last tertile of DTAC had a significantly decreased risk of HT (OR = 0.47; 95% CI = 0.23–0.98; P = 0.043) compared to those in the first tertile. The DII had a positive correlation with anti-thyroid peroxidase antibody (anti-TPO), thyroglobulin antibodies (TG-Ab) and thyroid-stimulating hormone, while DTAC had a negative correlation with anti-TPO and TG-Ab (P < 0.050). Conclusion: The increase in DII is not associated with an increase in the risk of HT, while DTAC can significantly reduce its risk. Having an anti-inflammatory and antioxidative diet can be effective in improving thyroid function. These conclusions should be confirmed in additional prospective studies. [ABSTRACT FROM AUTHOR]

Background: Micronutrients play pivotal roles in modulating various aspects of the immune response. However, the existing literature on the association between micronutrients and autoimmune thyroiditis (AIT) remains limited and contentious. To address this gap, we conducted Mendelian randomization (MR) to investigate potential links between genetically predicted concentrations of six micronutrients (Copper (Cu), Iron (Ir), Calcium (Ca), Vitamin D (VD), Vitamin C (VC), Zinc (Zn)) and the risk of AIT. Method: Utilizing summary statistics from genome-wide association studies (GWAS) in individuals of European descent, we employed MR methodologies to elucidate the interplay between micronutrients and AIT. Three distinct MR techniques were employed: Inverse Variance Weighted (IVW), MR-Egger regression, and Weighted Median Estimator (WME). Additionally, we evaluated outcome heterogeneity using Cochran’s Q statistic and assessed pleiotropy using the MR-Egger intercept. Result: IVW analysis revealed no substantial evidence supporting a significant impact of genetically predicted micronutrient concentrations on AIT risk (Cu: OR = 0.918, P = 0.875; Ir: OR = 0.653, P = 0.264; Ca: OR = 0.964, P = 0.906; VD: OR = 0.717, P = 0.378; VC: OR = 0.986, P = 0.875; Zn: OR = 0.789, P = 0.539). Cochran’s Q test for IVW indicated no notable heterogeneity. Moreover, the MREgger intercept method suggested the presence of horizontal pleiotropy between serum VC levels and AIT (MR-Egger intercept = −0.037, p = 0.026), while no such pleiotropy was observed for other micronutrients. Conclusion: Our MR analysis does not support a causal relationship between genetically predicted concentrations of six micronutrients (Cu, Ir, Ca, VD, VC, and Zn) and the risk of AIT. [ABSTRACT FROM AUTHOR]

Background: Alveolar macrophages activation to the pro-inflammatory phenotype M1 is pivotal in the pathophysiology of Ventilator-Induced Lung Injury (VILI). Increased lung strain is a known determinant of VILI, but a direct correspondence between regional lung strain and macrophagic activation remains unestablished. [68Ga]Ga-DOTA-TATE is a Positron Emission Tomography (PET) radiopharmaceutical with a high affinity for somatostatin receptor subtype 2 (SSTR2), which is overexpressed by pro-inflammatory-activated macrophages. Aim of the study was to determine, in a porcine model of VILI, whether mechanical strain correlates topographically with distribution of activated macrophages detected by [68Ga]Ga-DOTA-TATE uptake. Methods: Seven anesthetized pigs underwent VILI, while three served as control. Lung CT scans were acquired at incremental tidal volumes, simultaneously recording lung mechanics. [68Ga]Ga-DOTA-TATE was administered, followed by dynamic PET scans. Custom MatLab scripts generated voxel-by-voxel gas volume and strain maps from CT slices at para-diaphragmatic (Para-D) and mid-thoracic (Mid-T) levels. Analysis of regional Voxel-associated Normal Strain (VoStrain) and [68Ga]Ga-DOTA-TATE uptake was performed and a measure of the statistical correlation between these two variables was quantified using the linear mutual information (LMI) method. Results: Compared to controls, the VILI group exhibited statistically significant higher VoStrain and Standardized Uptake Value Ratios (SUVR) both at Para-D and Mid-T levels. Both VoStrain and SUVR increased along the gravitational axis with an increment described by statistically different regression lines between VILI and healthy controls and reaching the peak in the dependent regions of the lung (for strain in VILI vs. control was at Para-D: 760 ± 210 vs. 449 ± 106; at Mid-T level 497 ± 373 vs. 193 ± 160; for SUVR, in VILI vs. control was at Para-D: 2.2 ± 1.3 vs. 1.3 ± 0.1; at Mid-T level 1.3 ± 1.0 vs. 0.6 ± 0.03). LMI in both Para-D and Mid-T was statistically significantly higher in VILI than in controls. Conclusions: In this porcine model of VILI, we found a topographical correlation between lung strain and [68Ga]Ga-DOTA-TATE uptake at voxel level, suggesting that mechanical alteration and specific activation of inflammatory cells are strongly linked in VILI. This study represents the first voxel-by-voxel examination of this relationship in a multi-modal imaging analysis. [ABSTRACT FROM AUTHOR]

The global microplastic pollution issue, as a result of the indispensable usage of microplastics in building materials, packaged food, medical products and consumer goods, poses significant health problems for the population. These small particles can penetrate intact cell barriers in the intestines and alveoli, thereby entering the bloodstream. The aim of this pilot study was to investigate the effects of reduced plastic consumption on blood pressure. Eight adult and healthy participants abstained from consuming commercially produced bottled beverages and restricted their primary fluid intake to tap water. Blood pressure was measured on both sides before, after 14 days and after 28 to 30 days of this partial plastic diet. Women exhibit a significant change in systolic blood pressure on the right arm after 2 and 4 weeks, while the left arm demonstrates no significant changes in blood pressure. On the contrary, in men, systolic blood pressure values on both arms show no significant alterations, attributable to the high variability across the three participants. Moreover, no significant differences in systolic blood pressure were observed when analysing the entire cohort. Significant findings are evident only at the two-week mark for diastolic blood pressure for all participants in both arms. When considering diastolic blood pressure separately for women and men, men again show no significant changes in blood pressure on either arm. However, women exhibit a significant decrease in diastolic blood pressure on the left arm after 2 weeks and a statistically significant decline in diastolic blood pressure on the right arm after both 2 and 4 weeks. The results of the study suggest, for the first time, that a reduction in plastic use could potentially lower blood pressure, probably due to the reduced volume of plastic particles in the bloodstream. To confirm this hypothesis, a larger sample of male and female participants must be examined, ideally with the monitoring of plastic concentration in the blood. [ABSTRACT FROM AUTHOR]

According to the World Health Organization (WHO), the incidence of HCV remains high (around 1.5 million new patients every year), and 80% of patients with acute infection will progress to chronic hepatitis and develop cirrhosis and even liver cancer. Furthermore, some extrahepatic pathologies may be correlated with HCV (such as mixed cryoglobulinemia, porphyria cutanea tarda, lichen planus, glomerulonephritis, Sjogren's syndrome, Hodgkin and non-Hodgkin cell lymphoma, and others). In view of these secondary complications, together with the substantial risk of liver damage, the objective of this review was to research and suggest, based on the scientific evidence, the appropriate clinical use of drugs with direct antiviral action (AAD) according to the criteria of international medical organizations. This is to maximize the clinical benefits for patients and to facilitate access to DAA therapy for all patients with chronic hepatitis C. According to the WHO, no vaccine is currently available, and therapies using new antivirals and their combinations are now an effective and safer solution for patients than they have been in the past with the use of interferons. This study aims to analyse the history and knowledge of the pathogenic biomolecular mechanisms and current therapies for HCV. [ABSTRACT FROM AUTHOR]

Hormonal disorders like PCOS (Polycystic Ovary Syndrome), autoimmune thyroid disease (AITD) including Hashimoto's thyroiditis, male hypogonadism are commonly encountered in clinical practice in the US and worldwide, with rising frequency. These typically affect patients during young or middle age, compared with other common chronic illnesses like type 2 diabetes, hypertension, atherosclerotic cardiovascular disease, where onset may usually be in middle or older age. Multiple studies point to the role of disordered lifestyle health behaviors as contributory to these endocrinopathies, and conversely therapeutic lifestyle changes leading to improvement in signs, symptoms, biochemical markers, and sequelae of these conditions. This article presents 3 different real life case studies of the conditions enlisted above and documents the positive impact of lifestyle improvements on their disease condition. Therapeutic lifestyle behaviors are an extremely useful and important component of management of these familiar endocrinologic disorders, and clinicians need to routinely counsel their patients about healthy lifestyle interventions when treating these common syndromes. [ABSTRACT FROM AUTHOR]

Iodine at the ocean's surface impacts climate and health by removing ozone (O 3) from the troposphere both directly via ozone deposition to seawater and indirectly via the formation of iodine gases that are released into the atmosphere. Here we present a new box model of the ocean surface microlayer that couples oceanic O 3 dry deposition to inorganic chemistry to predict inorganic iodine emissions. This model builds on the previous work of , improving both chemical and physical processes. This new box model predicts iodide depletion in the top few micrometres of the ocean surface due to rapid chemical loss to ozone competing with replenishment from underlying water. From this box model, we produce parameterized equations for HOI and I 2 emissions, which are implemented into the global chemical transport model GEOS-Chem along with an updated sea surface iodide climatology. Compared to the previous model, inorganic iodine emissions from some tropical waters decrease by as much as half, while higher-latitude emissions increase by a factor of ≫10. With these large local changes, global total inorganic iodine emissions increased by ∼49 % (2.99 to 4.48 Tg) compared to the previous parameterization. This results in a negligible change in average tropospheric OH (<0.2 %) and tropospheric methane lifetime (<0.2 %). The annual mean tropospheric O 3 burden decreases (-1.5 % to 325 Tg); however, higher-latitude surface O 3 concentrations decrease by as much as 20 %. [ABSTRACT FROM AUTHOR]

The Geostationary Environment Monitoring Spectrometer (GEMS) launched in February 2020 is now providing continuous daytime hourly observations of nitrogen dioxide (NO 2) columns over eastern Asia (5° S–45° N, 75–145° E) with 3.5 × 7.7 km 2 pixel resolution. These data provide unique information to improve understanding of the sources, chemistry, and transport of nitrogen oxides (NO x) with implications for atmospheric chemistry and air quality, but opportunities for direct validation are very limited. Here we correct the operational level-2 (L2) NO 2 vertical column densities (VCDs) from GEMS with a machine learning (ML) model to match the much sparser but more mature observations from the low Earth orbit TROPOspheric Monitoring Instrument (TROPOMI), preserving the data density of GEMS but making them consistent with TROPOMI. We first reprocess the GEMS and TROPOMI operational L2 products to use common prior vertical NO 2 profiles (shape factors) from the GEOS-Chem chemical transport model. This removes a major inconsistency between the two satellite products and greatly improves their agreement with ground-based Pandora NO 2 VCD data in source regions. We then apply the ML model to correct the remaining differences, Δ (GEMS–TROPOMI), using the GEMS NO 2 VCDs and retrieval parameters as predictor variables. We train the ML model with colocated GEMS and TROPOMI NO 2 VCDs, taking advantage of TROPOMI off-track viewing to cover the wide range of effective zenith angles (EZAs) observed by GEMS. The two most important predictor variables for Δ (GEMS–TROPOMI) are GEMS NO 2 VCD and EZA. The corrected GEMS product is unbiased relative to TROPOMI and shows a diurnal variation over source regions more consistent with Pandora than the operational product. [ABSTRACT FROM AUTHOR]

SpikoGen® vaccine is a subunit COVID-19 vaccine composed of an insect cell expressed recombinant spike protein extracellular domain formulated with Advax-CpG55.2™ adjuvant. A randomized double-blind, placebo-controlled Phase II clinical trial was conducted in 400 adult subjects who were randomized 3:1 to receive two intramuscular doses three weeks apart of either SpikoGen® vaccine 25 μg or saline placebo, as previously reported. This study reports a post hoc analysis of the trial data to explore potential immune correlates of SpikoGen® vaccine protection. A range of humoral markers collected pre- and post-vaccination, including spike- and RBD-binding IgG and IgA, surrogate (sVNT), and conventional (cVNT) virus neutralization tests were compared between participants who remained infection-free or got infected over three months of follow-up. From 2 weeks after the second vaccine dose, 21 participants were diagnosed with SARS-CoV-2 infection, 13 (4.2%) in the SpikoGen® group and 8 (9%) in the placebo group. Those in the vaccinated group who experienced breakthrough infections had significantly lower sVNT titers (GMT 5.75 μg/mL, 95% CI; 3.72–8.91) two weeks after the second dose (day 35) than those who did not get infected (GMT 21.06 μg/mL, 95% CI; 16.57–26.76). Conversely, those who did not develop SARS-CoV-2 infection during follow-up had significantly higher baseline sVNT, cVNT, spike-binding IgG and IgA, and RBD-binding IgG, consistent with a past SARS-CoV-2 infection. SpikoGen® further reduced the risk of re-infection (OR 0.29) in baseline seropositive (previously infected) as well as baseline seronegative participants. This indicates that while SpikoGen vaccine is protective in seronegative individuals, those with hybrid immunity have the most robust protection. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the feasibility of using residues from cooking oil production to produce alternative biochar fuels along with optimizing the pyrolysis process. The work consisted of carrying out the pyrolysis process at varying temperatures and holding times at the final temperature, and then evaluating the energy potential of the materials studied. Taking into account aspects of environmental emissions, the content of selected oxides in the flue gases generated during the combustion of cakes and the biochar obtained from them was evaluated. Plant biomass derived from a variety of oilseeds, i.e., fennel flower (Nigella sativa L.), rapeseed (Brassica napus L. var. Napus), flax (Linum usitatissimum L.), evening primrose (Oenothera biennis L.), milk thistle (Silybum marianum L. Gaertn.) and hemp (Cannabis sativa L.), was used to produce biochar. The experimental data have shown that the obtained biochar can have a calorific value of nearly 27 MJ kg−1. The use of pyrolysis allowed for a maximum increase in the calorific value of nearly 41% compared to non-thermally processed cakes and a several-fold decrease in carbon monoxide, nitrogen oxides and sulfur dioxide emissions. According to these results, it can be concluded that the pyrolysis process can be an attractive method for using residues from the production of various cooking oils to produce alternative biofuels, developing the potential of the circular economy. [ABSTRACT FROM AUTHOR]

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Digital signatures are widely deployed to authenticate the source of incoming information, or to certify data integrity. Common signature verification procedures return a decision (accept/reject) only at the very end of the execution. If interrupted prematurely, however, the verification process cannot infer any meaningful information about the validity of the given signature. This limitation is due to the algorithm design solely, and it is not inherent to signature verification. In this work, we provide a formal framework to extract information from prematurely interrupted signature verification, independently of why the process halts: we propose a generic verification procedure that progressively builds confidence on the final decision. Our transformation builds on a simple but powerful intuition and applies to a wide range of existing schemes considered to be post-quantum secure, including some lattice-based and multivariate equations based constructions. We demonstrate the feasibility of our approach through an implementation on off-the-shelf resource-constrained devices. In particular, an intensive testing activity has been conducted measuring the increase of performance on three IoT boards—i.e., Arduino, Raspberry, and Espressif—and a consumer-grade laptop. While the primary motivation of progressive verification is to mitigate unexpected interruptions, we show that verifiers can leverage it in two innovative ways. First, progressive verification can be used to intentionally adjust the soundness of the verification process. Second, our transformation splits verification into a computationally intensive offline set-up (run once), and an efficient online verification that is faster than the original algorithm. We conclude showing how to tweak our compiler for progressive verification to work on a wide range of signatures with properties, on three real-life use cases, and in combination with efficient verification. [ABSTRACT FROM AUTHOR]

Purpose: In the present short report, we encompass the radiobiological and dosimetric advantages of particle beam radiotherapy and we illustrate the oncological pathway for patients eligible for hadrontherapy being used at the National Center for Oncological Hadrontherapy (CNAO). Methods: With a narrative approach, we examined the clinical and practical aspects of hadrontherapy compared to traditional photon beam radiotherapy. We described the need to select patients considering the intrinsic characteristics both of the tumour and the patient. Moreover, we described the decisional oncological tree and the patient pathway by our facility. Results: Considering the dosimetric and radiobiological characteristics of particle beam radiotherapy, the selection of patients can not be done regardless of the intrinsic tumour and patient hallmarks. In particular, the tumour radioresistance, the patient radiosensitivity and the need to avoid post-actinic toxicities in long-term survivors should guide the clinical indication. The finite range of particles should be considered to avoid treatment uncertainties. Multidisciplinary national and international collaboration is crucial to better manage patients to treat with hadrontherapy and to create robust clinical evidence. Conclusion: Hadrontherapy, with its distinctive physical and biological advantages, heralds a promising era in the field of precision radiotherapy. Patients' radiosensitivity, tumour radioresistance, and treatment uncertainties should be considered to enhance the efficacy and to ameliorate the selection of patients. [ABSTRACT FROM AUTHOR]

Stroke-induced spasticity is a prevalent condition affecting stroke survivors, significantly impacting their quality of life. Botulinum Toxin A injections are widely used for its management, yet the long-term effects and optimal management strategies remain uncertain. This retrospective study analyzed medical records of 95 chronic stroke patients undergoing long-term BoNT-A treatment for spasticity. Demographic data, treatment duration, dosage variability, and dropout rates were assessed over a period ranging from 2 to 14 years. The study revealed a notable extension of the interval between BoNT-A injections throughout the treatment duration. Dropout rates peaked during the initial 5 years of treatment, perhaps due to perceived treatment ineffectiveness. Additionally, a trend of escalating dosage was observed across all groups, indicating a potential rise in the severity of spasticity or changes in treatment response over time. BoNT-A injections emerged as the predominant treatment choice for managing post-stroke spasticity. The delayed initiation of BoNT-A treatment underscores the need for heightened awareness among healthcare providers to recognize and manage spasticity promptly post-stroke. Patients' expectations and treatment goals should be clearly defined to optimize treatment adherence, while the observed escalation in dosage and treatment intervals emphasizes the dynamic nature of spasticity and underscores the importance of monitoring long-term treatment outcomes. [ABSTRACT FROM AUTHOR]

The recent global COVID-19 pandemic has had a profound and enduring impact, resulting in substantial loss of life. The scientific community has responded unprecedentedly by investigating various aspects of the crisis, particularly focusing on the acute phase of COVID-19. The roles of the viral load, cytokines, and chemokines during the acute phase and in the context of patients who experienced enduring symptoms upon infection, so called Post-Acute Sequelae of COVID-19 or PASC, have been studied extensively. Here, in this review, we offer a virologist's perspective on PASC, highlighting the dynamics of SARS-CoV-2 viral loads, cytokines, and chemokines in different organs of patients across the full clinical spectrum of acute-phase disease. We underline that the probability of severe or critical disease progression correlates with increased viral load levels detected in the upper respiratory tract (URT), lower respiratory tract (LRT), and plasma. Acute-phase viremia is a clear, although not unambiguous, predictor of PASC development. Moreover, both the quantity and diversity of functions of cytokines and chemokines increase with acute-phase disease severity. Specific cytokines remain or become elevated in the PASC phase, although the driving factor of ongoing inflammation found in patients with PASC remains to be investigated. The key findings highlighted in this review contribute to a further understanding of PASC and their differences and overlap with acute disease. [ABSTRACT FROM AUTHOR]

Protein phosphatase 1 (PP1) complexes have emerged as promising targets for anticancer therapies. The ability of peptides to mimic PP1-docking motifs, and so modulate interactions with regulatory factors, has enabled the creation of highly selective modulators of PP1-dependent cellular processes that promote tumor growth. The major objective of this study was to develop a novel bioactive cell-penetrating peptide (bioportide), which, by mimicking the PP1-binding motif of caveolin-1 (CAV1), would regulate PP1 activity, to hinder prostate cancer (PCa) progression. The designed bioportide, herein designated CAVPENET, and a scrambled homologue, were synthesized using microwave-assisted solid-phase methodologies and evaluated using PCa cell lines. Our findings indicate that CAVPENET successfully entered PCa cells to influence both viability and migration. This tumor suppressor activity of CAVPENET was attributed to inhibition of AKT signaling, a consequence of increased PP1γ activity. This led to the suppression of glycolytic metabolism and alteration in lipid metabolism, collectively representing the primary mechanism responsible for the anticancer properties of CAVPENET. Our results underscore the potential of the designed peptide as a novel therapy for PCa patients, setting the stage for further testing in more advanced models to fully realize its therapeutic promise. [ABSTRACT FROM AUTHOR]

Due to their widespread misuse and inadequate waste management, single-use plastic bags represent the global plastic pollution crisis and ecosystem degradation. Comprehensive research on population knowledge, attitudes, and practices (KAP) regarding single-use plastic bags is lacking in the United Arab Emirates (UAE). This study aims to fill this gap by assessing the KAP levels among the UAE population and determining the relationships between these variables. A five-point Likert scale questionnaire from previous studies was used in a cross-sectional study, and the questionnaire was distributed via Google Forms. The UAE University Research Ethics Committee approved the study (ERSC_2024_4377). Non-probability sampling and G*power statistical analysis version 3.1.9.6 determined 385 UAE residents aged 18 years and older. The findings were verified through face-to-face interviews and Cronbach's alpha tests. KAP variable associations were assessed using Chi-square tests, Pearson's correlation coefficients, and a structural equation model with SPSS version 29.0. This test was chosen for robust categorical and continuous data. The study included 84.7% female, and 15.3% male participants aged 18 to 65 years, primarily aged 18 to 25 years, with most holding bachelor's degrees (47.6%), and were students (51.4%), employed (33.1%), or unemployed (12.2%). The results indicated a favourable inclination towards sustainability, with mean ± standard deviation (SD) for seven knowledge questions (3.89 ± 0.7), seven attitude questions (3.99 ± 0.7), and five practice questions (3.42 ± 0.8) exceeding the midpoint. The correlation test showed that total knowledge was positively correlated with practice (r = 0.399; p < 0.001) indicating the increasing knowledge regarding single-use plastic bags associated with increasing sustainable practices and attitudes (r = 0.648; p < 0.001). There was also a significant correlation between the total attitude and practice (r = 0.487; p < 0.001). The findings suggest targeted educational and policy interventions to promote sustainable behaviour. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) are highly bioactive molecules involved not only in tissue physiology but also in the development of different human conditions, including premature aging, cardiovascular pathologies, neurological and neurodegenerative disorders, inflammatory diseases, and cancer. Among the different human tumors, cutaneous melanoma, the most aggressive and lethal form of skin cancer, is undoubtedly one of the most well-known "ROS-driven tumor", of which one of the main causes is represented by ultraviolet (UV) rays' exposure. Although the role of excessive ROS production in melanoma development in pro-tumorigenic cell fate is now well established, little is known about its contribution to the progression of the melanoma metastatic process. Increasing evidence suggests a dual role of ROS in melanoma progression: excessive ROS production may enhance cellular growth and promote therapeutic resistance, but at the same time, it can also have cytotoxic effects on cancer cells, inducing their apoptosis. In this context, the aim of the present work was to focus on the relationship between cell redox state and the signaling pathways directly involved in the metastatic processes. In addition, oxidative or antioxidant therapeutic strategies for metastatic melanoma were also reviewed and discussed. [ABSTRACT FROM AUTHOR]

Large-scale reforestation, afforestation, and forest restoration schemes have gained global support as climate change mitigation strategies due to their significant carbon dioxide removal (CDR) potential. However, there has been limited research into the unintended consequences of forestation from a biophysical perspective. In the Community Earth System Model version 2 (CESM2), we apply a global forestation scenario, within a Paris Agreement-compatible warming scenario, to investigate the land surface and hydroclimate response. Compared to a control scenario where land use is fixed to present-day levels, the forestation scenario is up to 2 °C cooler at low latitudes by 2100, driven by a 10 % increase in evaporative cooling in forested areas. However, afforested areas where grassland or shrubland are replaced lead to a doubling of plant water demand in some tropical regions, causing significant decreases in soil moisture (∼ 5 % globally, 5 %–10 % regionally) and water availability (∼ 10 % globally, 10 %–15 % regionally) in regions with increased forest cover. While there are some increases in low cloud and seasonal precipitation over the expanded tropical forests, with enhanced negative cloud radiative forcing, the impacts on large-scale precipitation and atmospheric circulation are limited. This contrasts with the precipitation response to simulated large-scale deforestation found in previous studies. The forestation scenario demonstrates local cooling benefits without major disruption to global hydrodynamics beyond those already projected to result from climate change, in addition to the cooling associated with CDR. However, the water demands of extensive forestation, especially afforestation, have implications for its viability, given the uncertainty in future precipitation changes. [ABSTRACT FROM AUTHOR]

Background: Dysfunctional decision-making and intense craving represent pivotal aspects across all addictive behaviors, notably evident in gambling addiction where these factors significantly shape chasing behavior—continuing gambling to recoup losses—indicative of problematic gambling. This study explores the correlation between chasing behavior, craving, affective decision-making, decision-making styles, and gambling severity among habitual Italian gamblers. Methods: One hundred and sixty-six participants from diverse gambling venues completed assessments including the South Oaks Gambling Screen (SOGS), the Iowa Gambling Task (IGT), the General Decision-Making Style (GDMS), the Gambling Craving Scale (GACS), and a computerized task to measure chasing behavior. Participants were randomly assigned to Control and Loss chasing conditions. Results: Regression analyses revealed craving as a predictor of chasing behavior. Interestingly, individuals with a dependent decision-making style exhibited lower tendencies to chase. While IGT performance correlates with chasing frequency, it is not associated with the decision to continue or cease gambling. Intriguingly, gambling severity (SOGS total score) did not feature in the final models of both regression analyses. Discussion: These findings emphasize the significant role of craving in driving chasing behavior. Additionally, this study introduces, for the first time, the idea that a dependent decision-making style could potentially serve as a safeguard against chasing proneness. Conclusions: The study suggests a fundamental dichotomy between chasers and nonchasers among gamblers, irrespective of gambling severity. This distinction could be instrumental in tailoring more effective intervention strategies for gambling disorder treatment. [ABSTRACT FROM AUTHOR]

Lysosomes serve as catabolic centers and signaling hubs in cells, regulating a multitude of cellular processes such as intracellular environment homeostasis, macromolecule degradation, intracellular vesicle trafficking and autophagy. Alterations in lysosomal level and function are crucial for cellular adaptation to external stimuli, with lysosome dysfunction being implicated in the pathogenesis of numerous diseases. Osteoclasts (OCs), as multinucleated cells responsible for bone resorption and maintaining bone homeostasis, have a complex relationship with lysosomes that is not fully understood. Dysregulated function of OCs can disrupt bone homeostasis leading to the development of various bone disorders. The regulation of OC differentiation and bone resorption for the treatment of bone disease have received considerable attention in recent years, yet the role and regulation of lysosomes in OCs, as well as the potential therapeutic implications of intervening in lysosomal biologic behavior for the treatment of bone diseases, remain relatively understudied. This review aims to elucidate the mechanisms involved in lysosomal biogenesis and to discuss the functions of lysosomes in OCs, specifically in relation to differentiation, bone resorption, and autophagy. Finally, we explore the potential therapeutic implication of targeting lysosomes in the treatment of bone metabolic disorders. [ABSTRACT FROM AUTHOR]

Chronic pain is a debilitating symptom with a significant negative impact on the quality of life and socioeconomic status, particularly among adults and the elderly. Major Depressive Disorder (MDD) stands out as one of the most important comorbid disorders accompanying chronic pain. The kynurenine pathway serves as the primary route for tryptophan degradation and holds critical significance in various biological processes, including the regulation of neurotransmitters, immune responses, cancer development, metabolism, and inflammation. This review encompasses key research studies related to the kynurenine pathway in the context of headache, neuropathic pain, gastrointestinal disorders, fibromyalgia, chronic fatigue syndrome, and MDD. Various metabolites produced in the kynurenine pathway, such as kynurenic acid and quinolinic acid, exhibit neuroprotective and neurotoxic effects, respectively. Recent studies have highlighted the significant involvement of kynurenine and its metabolites in the pathophysiology of pain. Moreover, pharmacological interventions targeting the regulation of the kynurenine pathway have shown therapeutic promise in pain management. Understanding the underlying mechanisms of this pathway presents an opportunity for developing personalized, innovative, and non-opioid approaches to pain treatment. Therefore, this narrative review explores the role of the kynurenine pathway in various chronic pain disorders and its association with depression and chronic pain. [ABSTRACT FROM AUTHOR]

Through the Bayesian lens of four-dimensional variational (4D-Var) data assimilation, uncertainty in model parameters is traditionally quantified through the posterior covariance matrix. However, in modern settings involving high-dimensional and computationally expensive forward models, posterior covariance knowledge must be relaxed to deterministic or stochastic approximations. In the carbon flux inversion literature, proposed a stochastic method capable of approximating posterior variances of linear functionals of the model parameters that is particularly well suited for large-scale Earth-system 4D-Var data assimilation tasks. This note formalizes this algorithm and clarifies its properties. We provide a formal statement of the algorithm, demonstrate why it converges to the desired posterior variance quantity of interest, and provide additional uncertainty quantification allowing incorporation of the Monte Carlo sampling uncertainty into the method's Bayesian credible intervals. The methodology is demonstrated using toy simulations and a realistic carbon flux inversion observing system simulation experiment. [ABSTRACT FROM AUTHOR]

The properties of biochar may vary depending on feedstock type and producing temperature. The aim of this research was to understand the short-term effects of different pyrolysis temperatures and application rates of olive pomace biochar (OPB) on soil carbon (C), aggregate stability (AS), and aggregate size distribution for sandy loam soil. OPB was produced at low (350 °C) and high (700 °C) temperatures and incorporated into the soil at different rates and incubated for 6 months under controlled temperature and moisture conditions. OPB350 had low pH, high carbon, and nitrogen (N) values compared to OPB700. As the temperature increased the concentration of zinc, iron, manganese, copper, sodium, potassium, and magnesium in biochar increased. The BET surface area of OPB350 was 1.076 m2 g−1, and OPB 700 was 107.7 m2 g−1. Application of OPB improved soil aggregate stability and carbon content while the proportion of > 4 mm-aggregates and aggregate mean weight diameter decreased. OPB addition to soil increased microaggregate percentages and decreased macroaggregate percentages. OPB produced at high temperatures significantly increased soil AS value compared to OPB350. [ABSTRACT FROM AUTHOR]

Nanoplastics (NPs) represent an escalating hazard to both humans and the ecosystem due to their pervasive presence. This review delves into (i) the widespread occurrence of NPs across the different environmental matrices, including food; (ii) routes and estimates for human exposure; (iii) the mechanisms of blood–brain barrier (BBB) crossing; and (iv) implications for human health, with a specific focus on molecular features associated with neurotoxicity and neurodegenerative processes. The impact of NPs on the central nervous system, their ability to cross the BBB and the underpinning mechanisms, the potential to initiate neurotoxicity by fostering β-amyloid aggregation, and their interactions with metallo-enzymes (such as superoxide dismutase) are elucidated. The analysis of transcriptomics and epigenomic results, including microRNA dysregulation, unveil how NPs could contribute to neurological disorders. The need for considering overlaps among diverse pathogenetic mechanisms when probing the effects of NPs is discussed. Additional urgent needs are the development of reliable in vitro models for neurotoxicity studies able to mimic the complexity of the nervous system and the exposure of such models to more environmentally relevant NPs. Finally, the development of extremely sensitive detection and analysis methodologies to quantify NPs in environmental and biological matrices is a pressing priority. [ABSTRACT FROM AUTHOR]

Social controllability, or the ability to exert control during social interactions, is crucial for optimal decision-making. Inability to do so might contribute to maladaptive behaviors such as smoking, which often takes place in social settings. Here, we examined social controllability in nicotine-dependent humans as they performed an fMRI task where they could influence the offers made by simulated partners. Computational modeling revealed that smokers under-estimated the influence of their actions and self-reported a reduced sense of control, compared to non-smokers. These findings were replicated in a large independent sample of participants recruited online. Neurally, smokers showed reduced tracking of forward projected choice values in the ventromedial prefrontal cortex, and impaired computation of social prediction errors in the midbrain. These results demonstrate that smokers were less accurate in estimating their personal influence when the social environment calls for control, providing a neurocomputational account for the social cognitive deficits in this population. Pre-registrations: OSF Registries|How interoceptive state interacts with value-based decision-making in addiction (fMRI study). OSF Registries|COVID-19: social cognition, mental health, and social distancing (online study). A neurocomputational model of social forward thinking shows that smokers under-estimate the influence of their actions on future interactions, a cognitive deficit associated with aberrant prefrontal and midbrain activities. [ABSTRACT FROM AUTHOR]

This editorial published in the journal Frontiers in Endocrinology discusses the advancements in thyroid cancer research, specifically focusing on molecular characterization and prediction models for recurrence. The article emphasizes the importance of accurate molecular and genetic characterization to differentiate between less aggressive and more aggressive thyroid tumors. It also explores the use of biomarkers and prediction models to improve the diagnosis and management of thyroid nodules. The document provides a summary of three studies related to thyroid cancer research, which identify genes associated with recurrence, analyze the genetic landscape of thyroid cancer in Chinese patients, and investigate the shared molecular mechanisms between thyroid cancer and Hashimoto's thyroiditis. These studies contribute to our understanding of thyroid cancer and may lead to personalized treatment options. [Extracted from the article]

Introduction: Melanoma, a highly aggressive skin cancer originating in melanocytes, poses a significant threat due to its metastatic potential. While progress has been made in treating melanoma with targeted therapies and immunotherapies, challenges persist. Crotoxin (CTX), the principal toxin in Crotalus durissus terrificus snake venom, exhibits various biological activities, including anti-tumoral effects across multiple cancers. However, its clinical use is limited by toxicity. Thus, exploring alternatives to mitigate adverse effects is crucial. Methods and Results: This study investigates the antitumoral potential of CTX in its native and in a detoxified form, in melanoma cells. Firstly, we demonstrated that detoxified CTX presented reduced phospholipase activity. Both forms proved to be more cytotoxic to SK-MEL-28 and MeWo melanoma cells than nontumoral cells. In SK-MEL-28 cells, where cytotoxic effects were more pronounced, native and detoxified CTX induced increased necrosis and apoptosis rates. We also confirmed the apoptosis death demonstrated by the activation of caspase-3 and 7, and the formation of apoptotic bodies. Furthermore, both CTX caused cell cycle arrest at the G2/M phase, interfering with melanoma cell proliferation. Cell migration and invasion were also suppressed by both CTX. These results confirm the antitumoral potential of CTX. Discussion: The maintenance of the antiproliferative effects in the detoxified version, with reduced enzymatic activity often liked to harm effects, supports further studies to identify active parts of the molecule responsible for the interesting effects without causing substantial toxic events, contributing to the future use of CTX-derived drugs with safety and efficacy. [ABSTRACT FROM AUTHOR]

The number of unstable combinations of elastic and Stokes optical modes of the LIGO Voyager gravitational wave detector, frequencies and spatial distributions of displacement vectors of elastic modes of the mirrors were calculated. The values of overlap factors for unstable modes up to ninth-order optical modes were calculated, taking into account the azimuthal condition of parametric instability. An analysis of the influence of the temperature dependence of the Young's modulus of the mirror material on the number of unstable modes in the Fabry–Perot cavity was performed. [ABSTRACT FROM AUTHOR]

Simple Summary: The study investigated how aging affects the reproductive potential and embryonic development of the pepper weevil (Anthonomus eugenii Cano), a major pest causing significant damage to pepper crops. The objective was to assess the reproductive parameters (fecundity, hatching rates, and developmental times) of weevils at different ages: young (10 days), middle-aged (20 days), and old (30 days). The results show that the age of pepper weevils significantly affects their reproductive potential, with younger weevils being more prolific. These findings are valuable for researchers as they highlight the importance of considering weevil age in pest management strategies, potentially leading to more effective cultural practices that reduce weevil populations and protect pepper crops. The pepper weevil (Anthonomus eugenii Cano) is a devastating pest that inflicts severe damage to pepper crops, leading to substantial economic losses. This study investigated the impact of aging on the reproductive success of the pepper weevil. Pepper weevil-infested fruit were harvested from pepper fields and subsequently transferred into an insect cage to facilitate the emergence of adults. The emerged adults were housed in separate cages and allowed to mature until they reached specified ages: 10 days old (young), 20 days old (middle-aged), and 30 days old (old) individuals. Eggs laid by each age group were carefully collected and incubated under controlled laboratory conditions (28 ± 1.5 °C). Several reproductive variables including the number of eggs laid, the percentage of hatched eggs, and the egg incubation period were recorded for each age group. Embryonic development was also monitored daily using a VHX digital microscope at a magnification of 200×. Differences in developmental stages such as the blastoderm, germ band, gastrulation, segmentation, and appendage formation were observed, and the time span of every stage was recorded. The results show that the 10-day-old weevils laid the most eggs and had the highest hatching rate and the shortest developmental time. The 30-day-old weevils laid the fewest eggs and had the lowest hatching rate and longest developmental time. Thus, the pepper weevil age significantly influenced the fecundity, length of time for each embryonic development stage, hatching rate, and incubation period, and should be considered when studying the reproductive biology of this pest insect. This first report of the effect of aging on the reproductive potential of the pepper weevil should enable pepper growers to adopt cultural practices aimed at reducing the pepper weevil populations, thereby helping to protect their crop from this important pest. [ABSTRACT FROM AUTHOR]