P-phenylenediamine antioxidants and their quinone derivatives: A review of their environmental occurrence, accessibility, potential toxicity, and human exposure.

Substituted p-phenylenediamines (PPDs), a class of antioxidants, have been widely used to extend the lifespan of rubber products, such as tires and pipes. During use, PPDs will generate their quinone derivatives (PPD-Qs). In recent years, PPDs and PPD-Qs have been detected in the global environment. Among them, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q), the oxidation product of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), has been identified as highly toxic to coho salmon, with the lethal concentration of 50 % (LC50) being 95 ng/L, highlighting it as an emerging pollutant of great concern. This review summarizes the physicochemical properties, global environmental distribution, bioaccessibility, potential toxicity, human exposure risk, and green measures associated with PPDs and PPD-Qs. These chemicals exhibit lipophilicity, bioaccumulation potential, and poor aqueous stability. They have been found in water, air, dust, soil, and sediment worldwide, indicating their significance as emerging pollutants. Notably, current studies have identified electronic waste, such as discarded wires and cables, as a non-negligible source of PPDs and PPD-Qs, in addition to tire wear. PPDs and PPD-Qs exhibit strong bioaccumulation in aquatic organisms and mammals, with a tendency for biomagnification within the food web, posing health threats to humans. Available toxicity data indicate that PPDs and PPD-Qs have negative effects on aquatic organisms, mammals, and invertebrates. Acute exposure leads to death and acute damage, while long-term exposure can cause a series of adverse effects, including growth and development toxicity, reproductive toxicity, neurotoxicity, intestinal toxicity, and multi-organ damage. This paper discusses current research gaps and offers recommendations to understand better the occurrence, behavior, toxicity, and environmental exposure risks of PPDs and PPD-Qs.

Association of serum interleukin-2 with severity and prognosis in hospitalized patients with community-acquired pneumonia: a prospective cohort study.

The prior studies have shown that interleukin-2 (IL-2) exerts important roles in the pathological and physiological processes of lung diseases. However, the role of IL-2 in community-acquired pneumonia (CAP) is still uncertain. Through a prospective cohort study, our research will explore the correlations between serum IL-2 levels and the severity and prognosis in CAP patients. There were 267 CAP patients included. Blood samples were obtained. Serum IL-2 were tested by enzyme-linked immunosorbent assay (ELISA). Demographic traits and clinical characteristics were extracted. Serum IL-2 were gradually elevated with increasing severity scores in CAP patients. Correlation analyses revealed that serum IL-2 were connected with physiological parameters including liver and renal function in CAP patients. According to a logistic regression analysis, serum IL-2 were positively correlated with CAP severity scores. We also tracked the prognostic outcomes of CAP patients. The increased risks of adversely prognostic outcomes, including mechanical ventilation, vasoactive agent usage, ICU admission, death, and longer hospital length, were associated with higher levels of IL-2 at admission. Serum IL-2 at admission were positively associated with severe conditions and poor prognosis among CAP patients, indicated that IL-2 may involve in the initiation and development of CAP. As a result, serum IL-2 may be an available biomarker to guide clinicians in assessing the severity and determining the prognosis of CAP.

Polymetallic contamination drives indigenous microbial community assembly dominated by stochastic processes at Pb-Zn smelting sites.

Indigenous microbial communities in smelting areas are crucial for maintaining fragile ecosystem functions. However, the community assembly process and their responses to polymetallic pollution are poorly understood, especially the taxa in each bin from the amplicons that contributed to the assembly process. Herein, microbial diversity, co-occurrence patterns, assembly process and the intrinsic mechanisms across contamination gradients at a typical PbZn smelting site were systematically unravelled by high-throughput sequencing. The results showed a consistent compositional profile among the indigenous communities across sampling sites, wherein genera KD4-96 from Chloroflexi and Sphingomonas from Proteobacteria emerged as the most abundant taxa. Network modularity of the high- and middle-contaminated communities at Pb and Zn smelting sites was >0.44, indicating that community populations were clustered into modules to resist high heavy metal stress. Stochastic processes dominated the community assembly, with the greatest contribution from drift (DR), which was significantly correlated with Pb, Zn, Cr and Cu contents. What's particular was that the DR-controlled bins were dominated by Proteobacteria (typical r-strategists), while the HoS-controlled bins were by Chloroflexi (typical K-strategists). Furthermore, the proportion of DR in the bins dominated by Sphingomonadaceae (phylum Proteobacteria) increased gradually with the increase of heavy metal contents. These discoveries provide essential insights for community control in restoring and mitigating soil degradation at PbZn smelting sites.

Resolution of anti-LGI1-associated autoimmune encephalitis in a patient after treatment with efgartigimod.

BACKGROUND: Anti leucine-rich, glioma inactivated 1 (LGI1) antibody-associated autoimmune encephalitis (AE) is the second most common AE, where the trafficking and recycling of the pathogenic immunoglobulin (IgG) can be controlled by the neonatal crystallizable fragment receptor (FcRn), making the latter as a candidate therapeutic target. Efgartigimod is an antagonist of FcRn, its ability to increase the degradation of IgGs and improve the health and quality of life of patients. ADAPT trail indicated its rapid efficacy and safety on myasthenia gravis. However, there is currently no case reported using efgartigimod for the treatment of anti-LGI1-associated AE. CASE DESCRIPTION: The patient presented with five episodes of generalized tonic-clonic seizures in the past 2 weeks. The patient had no abnormal signs on magnetic resonance imaging. Electroencephalogram examinations showed an increase in bilateral symmetric or asymmetric slow activity, without any clear epileptic waves. The cerebrospinal fluid (CSF) examination results indicated a slight increase in protein (47 mg/dL). The anti-LGI1 antibody titer in serum was 1:100 and that in CSF was 1:3.2. The treatment with intravenous methylprednisolone 1000 mg once a day combined with levetiracetam tablets failed to completely control the patient's seizures. Thus, 10 mg/kg efgartigimod was administered intravenously once a week for 2 weeks. After 2 weeks of treatment, serum levels of anti-LGI1 antibody and IgG decreased and the patient's epilepsy did not recur in the next 3 months. CONCLUSIONS: This is the first case report of using efgartigimod to treat anti-LGI1-associated AE. The combination of efgartigimod and methylprednisolone resulted in favorable outcomes, indicating that this is an optional treatment plan.

Extracellular vesicles from alveolar macrophages harboring phagocytosed methicillin-resistant Staphylococcus aureus induce necroptosis.

Methicillin-resistant Staphylococcus aureus (MRSA) infection, a major cause of hospital- and community-acquired pneumonia, still has a high mortality rate. Extracellular vesicles (EVs), as crucial mediators of intercellular communication, have a significant impact on infectious diseases. However, the role of EVs from alveolar macrophages (AMs) in MRSA pneumonia remains unclear. We report that AMs phagocytose MRSA and release more EVs in mice with MRSA pneumonia. EVs from AMs harboring phagocytosed MRSA exhibit significant proinflammatory effects and induce necroptosis by delivering tumor necrosis factor α (TNF-α) and miR-146a-5p. Mechanically, the upregulated miR-146a-5p in these EVs enhances the phosphorylation of RIPK1, RIPK3, and MLKL by targeting TNF receptor-associated factor 6 (TRAF6), thereby promoting TNF-α-induced necroptosis. The combination of a TNF-α antagonist and an miR-146a-5p antagomir effectively improves the outcomes of mice with MRSA pneumonia. Overall, we reveal the pronecrotic effect of EVs from MRSA-infected AMs and provide a promising target for the prevention and treatment of MRSA pneumonia.

Discovery of Potent Selective HDAC6 Inhibitors with 5-Phenyl-1H-indole Fragment: Virtual Screening, Rational Design, and Biological Evaluation.

Among the HDACs family, histone deacetylase 6 (HDAC6) has attracted extensive attention due to its unique structure and biological functions. Numerous studies have shown that compared with broad-spectrum HDACs inhibitors, selective HDAC6 inhibitors exert ideal efficacy in tumor treatment with insignificant toxic and side effects, demonstrating promising clinical application prospect. Herein, we carried out rational drug design by integrating a deep learning model, molecular docking, and molecular dynamics simulation technology to construct a virtual screening process. The designed derivatives with 5-phenyl-1H-indole fragment as Cap showed desirable cytotoxicity to the various tumor cell lines, all of which were within 15 µM (ranging from 0.35 to 14.87 µM), among which compound 5i had the best antiproliferative activities against HL-60 (IC50 = 0.35 ± 0.07 µM) and arrested HL-60 cells in the G0/G1 phase. In addition, 5i exhibited better isotype selective inhibitory activities due to the potent potency against HDAC6 (IC50 = 5.16 ± 0.25 nM) and the reduced inhibitory activities against HDAC1 (selective index ≈ 124), which was further verified by immunoblotting results. Moreover, the representative binding conformation of 5i on HDAC6 was revealed and the key residues contributing 5i's binding were also identified via decomposition free-energy analysis. The discovery of lead compound 5i also indicates that virtual screening is still a beneficial tool in drug discovery and can provide more molecular skeletons with research potential for drug design, which is worthy of widespread application.

Corrigendum to: Mechanism of HSP90 Inhibitor in the Treatment of DSS-induced Colitis in Mice by Inhibiting MAPK Pathway and Synergistic Effect of Compound Sophorae Decoction.

A typographical error appeared in the title of the article "Mechanism of HSP90 Inhibitor in the Treatment of DSS-induced Colitis in Mice by Inhibiting MAPK Pathway and Synergistic Effect of Compound Sophora Decoction", published in Current Pharmaceutical Design, 2022; 28(42): 3456-3468 [1]. Details of the error and a correction are provided below. Original: Mechanism of HSP90 Inhibitor in the Treatment of DSS-induced Colitis in Mice by Inhibiting MAPK Pathway and Synergistic Effect of Compound Sophora Decoction Corrected: Mechanism of HSP90 Inhibitor in the Treatment of DSS-induced Colitis in Mice by Inhibiting MAPK Pathway and Synergistic Effect of Compound Sophorae Decoction We regret the error and apologize to readers. The original article can be found online at: https://www.eurekaselect.com/article/127740.

Genome-Wide Association Analysis and Genetic Parameters for Egg Production Traits in Peking Ducks.

Egg production traits are crucial in the poultry industry, including age at first egg (AFE), egg number (EN) at different stages, and laying rate (LR). Ducks exhibit higher egg production capacity than other poultry species, but the genetic mechanisms are still poorly understood. In this study, we collected egg-laying data of 618 Peking ducks from 22 to 66 weeks of age and genotyped them by whole-genome resequencing. Genetic parameters were calculated based on SNPs, and a genome-wide association study (GWAS) was performed for these traits. The SNP-based heritability of egg production traits ranged from 0.09 to 0.54. The GWAS identified nine significant SNP loci associated with AFE and egg number from 22 to 66 weeks. These loci showed that the corresponding alleles were positively correlated with a decrease in the traits. Moreover, three potential candidate genes (ENSAPLG00020011445, ENSAPLG00020012564, TMEM260) were identified. Functional enrichment analyses suggest that specific immune responses may have a critical impact on egg production capacity by influencing ovarian function and oocyte maturation processes. In conclusion, this study deepens the understanding of egg-laying genetics in Peking duck and provides a sound theoretical basis for future genetic improvement and genomic selection strategies in poultry.

Mediterranean diet and associations with the gut microbiota and pediatric-onset multiple sclerosis using trivariate analysis.

BACKGROUND: The interplay between diet and the gut microbiota in multiple sclerosis (MS) is poorly understood. We aimed to assess the interrelationship between diet, the gut microbiota, and MS. METHODS: We conducted a case-control study including 95 participants (44 pediatric-onset MS cases, 51 unaffected controls) enrolled from the Canadian Pediatric Demyelinating Disease Network study. All had completed a food frequency questionnaire ≤21-years of age, and 59 also provided a stool sample. RESULTS: Here we show that a 1-point increase in a Mediterranean diet score is associated with 37% reduced MS odds (95%CI: 10%-53%). Higher fiber and iron intakes are also associated with reduced MS odds. Diet, not MS, explains inter-individual gut microbiota variation. Several gut microbes abundances are associated with both the Mediterranean diet score and having MS, and these microbes are potential mediators of the protective associations of a healthier diet. CONCLUSIONS: Our findings suggest that the potential interaction between diet and the gut microbiota is relevant in MS.

Multiple sclerosis (MS) is a disease where the immune system attacks the protective covering of nerve cells in the brain. There may be a relationship between diet and bacteria within the gut and MS, however this is not well understood. We investigated how diet and gut bacteria are linked to MS in young people. We examined the diet and types of bacteria in stool samples from those with and without MS. We found that a diet richer in fiber and Mediterranean foods were less common in those with MS. This dietary pattern was linked to certain differences in the gut bacteria. These findings raise the possibility, but cannot prove, that what we eat may help prevent MS by influencing our gut bacteria. This research opens the door to further studies on how diet can impact MS through our gut bacteria.

Large Language Model-Based Natural Language Encoding Could Be All You Need for Drug Biomedical Association Prediction.

Analyzing drug-related interactions in the field of biomedicine has been a critical aspect of drug discovery and development. While various artificial intelligence (AI)-based tools have been proposed to analyze drug biomedical associations (DBAs), their feature encoding did not adequately account for crucial biomedical functions and semantic concepts, thereby still hindering their progress. Since the advent of ChatGPT by OpenAI in 2022, large language models (LLMs) have demonstrated rapid growth and significant success across various applications. Herein, LEDAP was introduced, which uniquely leveraged LLM-based biotext feature encoding for predicting drug-disease associations, drug-drug interactions, and drug-side effect associations. Benefiting from the large-scale knowledgebase pre-training, LLMs had great potential in drug development analysis owing to their holistic understanding of natural language and human topics. LEDAP illustrated its notable competitiveness in comparison with other popular DBA analysis tools. Specifically, even in simple conjunction with classical machine learning methods, LLM-based feature representations consistently enabled satisfactory performance across diverse DBA tasks like binary classification, multiclass classification, and regression. Our findings underpinned the considerable potential of LLMs in drug development research, indicating a catalyst for further progress in related fields.

Interactions between organic matter and alkaline minerals in bauxite residue: implication for soil restoration.

Ecological restoration of bauxite residue has received extensive attention, and organic matter plays a crucial role in the soil formation process of bauxite residue. However, the interaction between organic matter and alkaline minerals in bauxite residue is not well understood. In this work, molecular spectroscopic techniques combined with isothermal titration calorimetry (ITC) were employed to investigate the interactions between humic acid (HA) and four representative alkaline minerals in bauxite residue (calcite, garnet, sodalite, and cancrinite). The results show that the adsorption processes of HA onto calcite and garnet were primarily governed by monolayer surface adsorption and controlled by surface reactions, which were different for sodalite and cancrinite. Both garnet and cancrinite had strong binding affinities with fluorescent HA, while cancrinite only bound with a small fraction of HA. In contrast, the bindings of calcite and sodalite with fluorescent HA were weak. The ITC results indicate distinct thermodynamic properties of different alkaline minerals in the interaction with HA. The molar enthalpy of calcite was - 45.88 kJ/mol, which was much higher than those of garnet, sodalite, and cancrinite, suggesting that calcite exhibited a relatively uniform interaction mechanism with HA dominated by enthalpy change, while the others showed heterogeneous entropy-driven mechanisms. The findings contribute to a better understanding on the microscale connections between organic matter and alkaline minerals in bauxite residue.

The Effect of Hemithyroidectomy in Papillary Thyroid Carcinoma with an Exclusive Involvement of the Recurrent Laryngeal Nerve: A Retrospective Study with a Propensity Score-Matched Analysis.

BACKGROUND: Involvement of the recurrent laryngeal nerve (RLN) in papillary thyroid carcinoma (PTC) is an important prognostic factor and is associated with a higher risk of recurrence. This study aimed to retrospectively analyze the outcomes of patients treated with hemithyroidectomy (HT) in PTC patients with an exclusive RLN invasion who could not tolerate staged surgery, did not wish to undergo another operation, or had other reasons. METHODS: A retrospective review was conducted on 163 patients with PTC and exclusive RLN involvement at our institution between 2013 and 2019. Patients were divided into a total thyroidectomy (TT) group and HT group. The clinicopathologic factors and prognostic outcomes were compared between the two groups. A propensity score-matched analysis was carried out to reduce selection bias, with the following covariates: gender, age, tumor size, multifocality, central lymph node metastasis (CLNM), and RLN resection. The Kaplan-Meier method was used for a comparison of recurrence outcomes. RESULTS: In the baseline data of the 163 PTC patients, tumor size (p < 0.001), multifocality (p = 0.011), CLNM (p < 0.001), and RLN resection (p < 0.008) in the TT and HT groups differed significantly, whereas age and gender did not differ between the two groups. The TT group reported significantly higher temporary and permanent hypoparathyroidism than the HT group (p < 0.001 and p = 0.042, respectively). With 72-month median follow-up, 11 (6.7%) patients developed recurrence. After propensity score matching, 24 patients with HT and 43 patients with TT were included. Recurrence-free survival (RFS) in the matched samples showed no difference between the TT and HT groups (p = 0.092). CONCLUSION: Our results indicate that HT may be a feasible treatment for PTC patients with exclusive RLN involvement in specific circumstances without significantly increasing the risk of recurrence. Performing a thorough preoperative examination is crucial to exclude multifocal tumors and lymph node metastasis before undergoing HT.

Metagenomic analysis revealed the association between gut microbiota and different ovary responses to controlled ovarian stimulation.

The aim of this study was to assess the correlation between gut microbial taxonomy and various ovarian responses to controlled ovarian stimulation. A total of 22 IVF cycles with a follicle-to-oocyte index (FOI) < 0.5 and 25 IVF cycles with FOI ≥ 0.5 were included in this study. Baseline demographic characteristics were compared between the two groups. Metagenomic sequencing was performed to analyze fecal microbial community profiles. Mice were used to evaluate the effect of Bifidobacterium_longum on ovarian response to stimulation. Compared with FOI < 0.5 group, women in group with FOI ≥ 0.5 had significant more oocytes retrieved (p < 0.01). Prevotella_copri, Bateroides_vulgatus, Escherichia_coli and Bateroides_stercoris were more abundant in FOI < 0.5 group while Bifidobacterium_longum, Faecalibacterium_prausnitzii, Ruminococcus_gnavus and Bifidobacterium_pseudocatenula were more abundant in FOI ≥ 0.5 group. After adjusting for women's age and BMI, Pearson correlation analysis indicated alteration of gut microbiome was related with serum E2, FSH, number of oocytes retrieved and clinical pregnancy rate. Animal study showed ovarian response will be improved after Bifidobacterium_longum applied. An increased abundance of Bacteroidetes and Prevotella copri, as well as a decreased abundance of Bifidobacterium longum, have been found to be associated with poor ovarian responsiveness. Changes in gut microbiomes have been observed to be correlated with certain clinical characteristics. The potential enhancement of ovarian response may be facilitated by the integration of Bifidobacterium longum.

Palladium-catalyzed Suzuki-Miyaura cross-couplings of stable glycal boronates for robust synthesis of C-1 glycals.

C-1 Glycals serve as pivotal intermediates in synthesizing diverse C-glycosyl compounds and natural products, necessitating the development of concise, efficient and user-friendly methods to obtain C-1 glycosides is essential. The Suzuki-Miyaura cross-coupling of glycal boronates is notable for its reliability and non-toxic nature, but glycal donor stability remains a challenge. Herein, we achieve a significant breakthrough by developing stable glycal boronates, effectively overcoming the stability issue in glycal-based Suzuki-Miyaura coupling. Leveraging the balanced reactivity and stability of our glycal boronates, we establish a robust palladium-catalyzed glycal-based Suzuki-Miyaura reaction, facilitating the formation of various C(sp2)-C(sp), C(sp2)-C(sp2), and C(sp2)-C(sp3) bonds under mild conditions. Notably, we expand upon this achievement by developing the DNA-compatible glycal-based cross-coupling reaction to synthesize various glycal-DNA conjugates. With its excellent reaction reactivity, stability, generality, and ease of handling, the method holds promise for widespread appication in the preparation of C-glycosyl compounds and natural products.

Challenges and Advancements in the Electrochemical Utilization of Ammonia Using Solid Oxide Fuel Cells.

Solid oxide fuel cells utilized with NH3 (NH3-SOFCs) have great potential to be environmentally friendly devices with high efficiency and energy density. The advancement of this technology is hindered by the sluggish kinetics of chemical or electrochemical processes occurring on anodes/catalysts. Extensive efforts have been devoted to developing efficient and durable anode/catalysts in recent decades. Although modifications to the structure, composition, and morphology of anodes or catalysts are effective, the mechanistic understandings of performance improvements or degradations remain incompletely understood. This review informatively commences by summarizing existing reports on the progress of NH3-SOFCs. It subsequently outlines the influence of factors on the performance of NH3-SOFCs. The degradation mechanisms of the cells/systems are also reviewed. Lastly, the persistent challenges in designing highly efficient electrodes/catalysts for low-temperature NH3-SOFCs, and future perspectives derived from SOFCs are discussed. Notably, durability, thermal cycling stability, and power density are identified as crucial indicators for enhancing low-temperature (550 °C or below) NH3-SOFCs. This review aims to offer an updated overview of how catalysts/electrodes affect electrochemical activity and durability, offering critical insights for improving performance and mechanistic understanding, as well as establishing the scientific foundation for the design of electrodes for NH3-SOFCs.

Pb/As simultaneous removal from soil leachate of Pb/Zn smelting sites by magnetic biochar.

Lead (Pb) and arsenic (As) contaminated soils, caused by Pb and zinc (Zn) smelting activities, pose an urgent environmental issue. Magnetic biochar (MB) has been regarded as an increasingly appealing candidate for the remediation of multi-metals in contaminated soils or their leachate. Finding economically feasible preparation methods for MB and demonstrating its remediation potential is desperately required for the remediation of such complex smelting sites. In this study, a modified MB was prepared using an optimized co-precipitation method, and its application potential for Pb/As simultaneous removal based on the basic properties of a typical Pb/Zn smelting site was evaluated. The surface modifications of MB facilitated the encapsulation of various ultrafine iron oxide particles, predominantly γ-Fe2O3 and Fe3O4, whilst notably enhancing the presence of oxygen-containing surface functional groups. The adsorption of Pb(II) and As(III) by MB was well-described using the pseudo-second-order adsorption and Langmuir models. The existence of SO42- and Ca2+ in the soil leachate competed with the adsorption sites for Pb(II) and As(III). Notably, within the pH range of 5-9, the adsorption efficiency of Pb(II) by MB increased with the rising solution pH, whereas alterations in pH minimally affected the removal rate of As(III), maintaining a consistent removal rate exceeding 95%. Furthermore, dissolved organic matter (DOM) abundant in organic functional groups, particularly CO and CC groups, significantly augmented the adsorption affinity for both Pb(II) and As(III). An application rate of 2 g/L could effectively reduce the concentration of Pb(II) and As(III) in soil leachate to <0.05 mg/L. The findings demonstrated the potential of the prepared MB for simultaneous removal of As(III) and Pb(II) in soil leachate, which should be beneficial to multi-metals polluted soil remediation in Pb/Zn smelting sites.

TOPK Inhibition Enhances the Sensitivity of Colorectal Cancer Cells to Radiotherapy by Reducing the DNA Damage Response.

OBJECTIVE: Abnormal expression of T-lymphokine-activated killer cell-originated protein kinase (TOPK) was reported to be closely related to the resistance of prostate cancer to radiotherapy and to targeted drug resistance in lung cancer. However, the role of TOPK inhibition in enhancing radiosensitivity of colorectal cancer (CRC) cells is unclear. This study aimed to evaluate the radiosensitization of TOPK knockdown in CRC cells. METHODS: The expression of TOPK was detected in CRC tissues by immunohistochemistry, and the effect of TOPK knockdown was detected in CRC cells by Western blotting. CCK-8 and clonogenic assays were used to detect the growth and clonogenic ability of CRC cells after TOPK knockdown combined with radiotherapy in CRC cells. Furthermore, proteomic analysis showed that the phosphorylation of TOPK downstream proteins changed after radiotherapy. DNA damage was detected by the comet assay. Changes in the DNA damage response signaling pathway were analyzed by Western blotting, and apoptosis was detected by flow cytometry. RESULTS: The expression of TOPK was significantly greater in CRC tissues at grades 2-4 than in those at grade 1. After irradiation, CRC cells with genetically silenced TOPK had shorter comet tails and reduced expression levels of DNA damage response-associated proteins, including phospho-cyclin-dependent kinase 1 (p-CDK1), phospho-ataxia telangiectasia-mutated (p-ATM), poly ADP-ribose polymerase (PARP), and meiotic recombination 11 homolog 1 (MRE11). CONCLUSIONS: TOPK was overexpressed in patients with moderately to poorly differentiated CRC. Moreover, TOPK knockdown significantly enhanced the radiosensitivity of CRC cells by reducing the DNA damage response.

OPTICS: An interactive online platform for photosensory and bio-functional proteins in optogenetic systems.

High-precise modulation of bio-functional proteins related to signaling is crucial in life sciences and human health. The cutting-edge technology of optogenetics, which combines optical method with genetically encoded protein expression, pioneered new pathways for the control of cellular bio-functional proteins (CPs) using optogenetic tools (OTs) in spatial and temporal. Over the past decade, hundreds of optogenetic systems (OSs) have been developed for various applications from living cells to freely moving organisms. However, no database has been constructed to comprehensively provide the valuable information of OSs yet. In this work, a new database named OPTICS (an interactive online platform for photosensory and bio-functional proteins in optogenetic systems) is introduced. Our OPTICS is unique in (i) systematically describing diverse OSs from the perspective of photoreceptor-based classification and mechanism of action, (ii) featuring the detailed biophysical properties and functional data of OSs, (iii) providing the interaction between OT and CP for each OS referring to distinct applications in research, diagnosis, and therapy, and (iv) enabling a light response property-based search against all OSs in the database. Since the information on OSs is essential for rapid and predictable design of optogenetic controls, the comprehensive data provided in OPTICS lay a solid foundation for the future development of novel OSs. OPTICS is freely accessible without login requirement at https://idrblab.org/optics/.

Seeing Beyond the Surface: Superior performance of Ultrasound elastography over Milan ultrasound criteria in distinguishing fibrosis of ulcerative colitis.

BACKGROUND: Colonic fibrosis has important clinical implications in ulcerative colitis. Ultrasound imaging has emerged as a convenient and reliable tool in diagnosis of inflammatory bowel disease. We aimed to explore the potential use of ultrasound to evaluate UC fibrosis. METHODS: Consecutive UC patients who had proctocolectomy from July 2022 to Sep 2023 were enrolled in the study. Patients underwent bowel ultrasound examination and ultrasound elastography imaging prior to surgery. Milan ultrasound criteria (MUC) was calculated and bowel wall stiffness was determined using two mean strain ratios (MSRs). Degree of colonic fibrosis and inflammation was measured upon histological analysis. ROC analysis was used to evaluate the performance of ultrasound-derived parameters to predict fibrosis. RESULTS: Fifty-six patients were enrolled with 112 segments included in analysis. The median fibrosis score was 2 (0-4) and the median Geboes score was 5 (0-13) and these two scores were significantly correlated (p<0.001). The muscularis mucosa thickness was significantly higher in moderate-severe fibrosis than none-mild fibrosis (p=0.003) but bowel wall thickness was not (p=0.082). The strain ratios (p<0.001) and MUC (p=0.010) was significantly higher in involved than non-involved segments. The strain ratios were correlated with fibrosis score (p<0.001) but not MUC (p=0.387). At ROC analysis, MSR1 had an AUC of 0.828 (cutoff value 3.07, 95% CI 0.746-0.893, p<0.001) to predict moderate-severe fibrosis. CONCLUSION: Ultrasound elastography imaging could predict the degree of colonic fibrosis in UC. Application of this technique could help disease monitoring and decision-making of UC patients.