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Macrophages are essential for the development of steatosis, hepatic inflammation, and fibrosis in metabolic dysfunction‐associated steatohepatitis(MASH). However, the roles of macrophage E2F2 in the progression of MASH have not been elucidated. This study reveals that the expression of macrophage E2F2 is dramatically downregulated in MASH livers from mice and humans, and that this expression is adversely correlated with the severity of the disease. Myeloid‐specific E2F2 depletion aggravates intrahepatic inflammation, hepatic stellate cell activation, and hepatocyte lipid accumulation during MASH progression. Mechanistically, E2F2 can inhibit the SLC7A5 transcription directly. E2F2 deficiency upregulates the expression of SLC7A5 to mediate amino acids flux, resulting in enhanced glycolysis, impaired mitochondrial function, and increased macrophages proinflammatory response in a Leu‐mTORC1‐dependent manner. Moreover, bioinformatics analysis and CUT &Tag assay identify the direct binding of Nrf2 to E2F2 promoter to promote its transcription and nuclear translocation. Genetic or pharmacological activation of Nrf2 effectively activates E2F2 to attenuate the MASH progression. Finally, patients treated with CDK4/6 inhibitors demonstrate reduced E2F2 activity but increased SLC7A5 activity in PBMCs. These findings indicated macrophage E2F2 suppresses MASH progression by reprogramming amino acid metabolism via SLC7A5‐ Leu‐mTORC1 signaling pathway. Activating E2F2 holds promise as a therapeutic strategy for MASH. [ABSTRACT FROM AUTHOR]

Chemical analysis showed that pH, b* values, myosin turbidity, carbonyl content, and surface hydrophobicity elevated in hooked, trawl‐net, and radar‐net hairtail (Trichiurus haumela, HH, TH, and RH) muscles with the prolonged cryopreservation time (‐18℃, 120 d). In contrast, L*, a* values, textural properties, and myosin solubility existed decreasing trends. Microstructural results showed that freezing resulted in disordered myofibrils, decreased collagen fibers, widened myofibrillar space, and increased fragmentation in hairtail muscles. Furthermore, volatile flavor analysis suggested that aldehydes, ketones, alcohols, and amines were the key factors for the overall flavor formation in hairtails during cold storage. Pearson correlation coefficient analysis revealed that the color, texture, and protein oxidation had close correlations with VOCs. Among the three different kinds of hairtail, fresh RH fillets exhibited an attractive aroma with high economic value, long‐term frozen TH muscle tissues were prone to deterioration in texture, microstructure, and flavor, and the HH samples presented stable quality characteristics and storage performance. [ABSTRACT FROM AUTHOR]

Cortical bone loss is intricately associated with ageing and coincides with iron accumulation. The precise role of ferroptosis, characterized by iron overload and lipid peroxidation, in senescent osteocytes remains elusive. We found that ferroptosis was a crucial mode of osteocyte death in cortical bone during ageing. Using a single‐cell transcriptome analysis, we identified activating transcription factor 3 (ATF3) as a critical driver of osteocyte ferroptosis. Elevated ATF3 expression in senescent osteocytes promotes iron uptake by upregulating transferrin receptor 1 while simultaneously inhibiting solute carrier family 7‐member 11‐mediated cystine import. This process leads to an iron overload and lipid peroxidation, culminating in ferroptosis. Importantly, ATF3 inhibition in aged mice effectively alleviated ferroptosis in the cortical bone and mitigated cortical bone mass loss. Taken together, our findings establish a pivotal role of ferroptosis in cortical bone loss in older adults, providing promising prevention and treatment strategies for osteoporosis and fractures. [ABSTRACT FROM AUTHOR]

For its vital role in maintaining cellular activity and survival, mitochondrion is highly involved in various diseases, and several strategies to target mitochondria have been developed for specific imaging and treatment. Among these approaches, theranostic may realize both diagnosis and therapy with one integrated material, benefiting the simplification of treatment process and candidate drug evaluation. A variety of mitochondria‐targeting theranostic agents have been designed based on the differential structure and composition of mitochondria, which enable more precise localization within cellular mitochondria at disease sites, facilitating the unveiling of pathological information while concurrently performing therapeutic interventions. Here, progress of mitochondria‐targeting theranostic materials reported in recent years along with background information on mitochondria‐targeting and therapy have been briefly summarized, determining to deliver updated status and design ideas in this field to readers. [ABSTRACT FROM AUTHOR]

The use of fruit fibres as a way of reusing industrial waste is attractive and necessary, increasing the efficiency and reducing the environmental impact of the industry. This study characterized guava fibre as a fibrous ingredient and evaluated its effects when included in extruded diets for dogs on nutrient digestibility, faecal traits, fermentation products, gastrointestinal transit time and palatability. Four diets were formulated: CO (control diet, no fibrous ingredients added), GF3 (3% guava fibre), GF6 (6% guava fibre) and GF12 (12% guava fibre). The guava fibre was added to diets in replacement of maize, with small adjustments in the other ingredients to ensure similar contents of protein and fat. The diets were fed to 24 adult Beagle dogs (6 per diet) during 15 days for adaptation followed by 15 days for assessment of digestibility, fermentation end products and gastrointestinal transit time. The palatability of G6 and G12 treatments was evaluated against the CO by the two‐pan test. Results were compared by analysis of variance and polynomial contrasts according to the guava fibre inclusion level (p < 0.05). The addition of guava fibre did not change nutrient intake except for the increase on dietary fibre (p < 0.001). Fibre inclusion resulted in a quadratic reduction in total tract apparent digestibility for dry matter, organic matter, crude protein and crude energy (p < 0.001), and on the metabolizable energy content of the foods (p < 0.001). Guava fibre addition did not change the faecal concentration of ammonia, lactic acid, faecal pH and branched chain fatty acids but it decreased acetic and propionic acids concentration (p < 0.01). The inclusion of 12% guava fibre did result in a faster transit time (p = 0.046) compared to the control diet. Guava fibre can be characterized as a novel insoluble non‐fermentable fibre source that could be safely used in levels up to 12% in canine extruded diets. [ABSTRACT FROM AUTHOR]

Label‐free blood typing by Raman spectroscopy (RS) is demonstrated by training an artificial intelligence (AI) model on 271 blood typed donor whole blood samples. A fused silica micro‐capillary flow cell enables fast generation of a large dataset of Raman spectra of individual donors. A combination of resampling methods, machine learning and deep learning is used to classify the ABO blood group, 27 erythrocyte antigens, 4 platelet antigens, regular anti‐B titers of blood group A donors, regular anti‐A,‐B titers of blood group O donors, and ABH‐secretor status, from a single Raman spectrum. The average area under the curve value of the ABO classification is 0.91 ± 0.03 and 0.72 ± 0.09, respectively, for the remaining traits. The classification performance of all parameters is discussed in the context of dataset balance and antigen concentration. Post‐hoc scalability analysis of the models shows the potential of RS and AI for future applications in transfusion medicine and blood banking. [ABSTRACT FROM AUTHOR]

The photocyclization reaction of sterically demanding styrylpyridine derivatives was investigated and shown to depend on the type of substituent. With this method, a 2,2‐diphenyl‐1,3‐benzodioxolo‐annelated benzo[c]quinolizinium was synthesized, and its association with regular and abasic site‐containing DNA (AP‐DNA) was investigated by absorption, fluorescence, circular and linear dichroism spectroscopy. Specifically, this ligand binds preferentially to AP‐DNA relative to regular duplex DNA, and the AP‐DNA/ligand complex is formed in situ upon irradiation of the styrylpyridine substrate in the presence of the DNA. [ABSTRACT FROM AUTHOR]

Lignin‐modifying enzymes (LMEs), which include laccases (Lacs), manganese peroxidases (MnPs), versatile peroxidases (VPs), and lignin peroxidases (LiPs), have been considered key factors in lignin degradation by white‐rot fungi because they oxidize lignin model compounds and depolymerize synthetic lignin in vitro. However, it remains unclear whether these enzymes are essential/important in the actual degradation of natural lignin in plant cell walls. To address this long‐standing issue, we examined the lignin‐degrading abilities of multiple mnp/vp/lac mutants of Pleurotus ostreatus. One vp2/vp3/mnp3/mnp6 quadruple‐gene mutant was generated from a monokaryotic wild‐type strain PC9 using plasmid‐based CRISPR/Cas9. Also, two vp2/vp3/mnp2/mnp3/mnp6, two vp2/vp3/mnp3/mnp6/lac2 quintuple‐gene mutants, and two vp2/vp3/mnp2/mnp3/mnp6/lac2 sextuple‐gene mutants were generated. The lignin‐degrading abilities of the sextuple and vp2/vp3/mnp2/mnp3/mnp6 quintuple‐gene mutants on the Beech wood sawdust medium reduced drastically, but not so much for those of the vp2/vp3/mnp3/mnp6/lac2 mutants and the quadruple mutant strain. The sextuple‐gene mutants also barely degraded lignin in Japanese Cedar wood sawdust and milled rice straw. Thus, this study presented evidence that the LMEs, especially MnPs and VPs, play a crucial role in the degradation of natural lignin by P. ostreatus for the first time. [ABSTRACT FROM AUTHOR]

Genomic DNA adopts B‐form canonically. Besides, the oligonucleotides can adopt various non‐canonical secondary structures. These are hairpins, cruciforms, triplexes, quadruplexes (G4), i‐motifs etc. G4s are usually formed by the guanine rich oligonucleotides and are found in both DNA and RNA. G4s are more frequently distributed in telomeres, promoter oncogenes, immunoglobulin switch regions, ribosomal DNA etc. Recently, it has been established that G4s are intriguingly connected with different human diseases including cancer. Stabilization of G4s by designed molecules or drugs impedes the transcription of several oncogenes and also creates encumbrance to the telomere biogenesis which is very important in impediment of cancer. G4 is treated as an important molecular target in the discovery of anti‐cancer drugs. Among the G4 targeting molecules, peptides draw sincere attention due to its small size, simple synthetic methodology, low cytotoxicity and cellular permeability. In this review, our main discussion revolves around the formation of G4, distribution of G4 in genome, structurally diverse peptides (linear, cyclic, branch, conjugated) having potential to target G4 structures and its future perspectives. [ABSTRACT FROM AUTHOR]

Tissue regeneration is regulated by morphological clues of implants in bone defect repair. Engineered morphology can boost regenerative biocascades that conquer challenges such as material bioinertness and pathological microenvironments. Herein, a correlation between the liver extracellular skeleton morphology and the regenerative signaling, namely hepatocyte growth factor receptor (MET), is found to explain the mystery of rapid liver regeneration. Inspired by this unique structure, a biomimetic morphology is prepared on polyetherketoneketone (PEKK) via femtosecond laser etching and sulfonation. The morphology reproduces MET signaling in macrophages, causing positive immunoregulation and optimized osteogenesis. Moreover, the morphological clue activates an anti‐inflammatory reserve (arginase‐2) to translocate retrogradely from mitochondria to the cytoplasm due to the difference in spatial binding of heat shock protein 70. This translocation enhances oxidative respiration and complex II activity, reprogramming the metabolism of energy and arginine. The importance of MET signaling and arginase‐2 in the anti‐inflammatory repair of biomimetic scaffolds is also verified via chemical inhibition and gene knockout. Altogether, this study not only provides a novel biomimetic scaffold for osteoporotic bone defect repair that can simulate regenerative signals, but also reveals the significance and feasibility of strategies to mobilize anti‐inflammatory reserves in bone regeneration. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a common malignancy affecting many people worldwide. Baicalin is a flavonoid extracted from the dried root of Scutellaria baicalensis Georgi. It can effectively inhibit the occurrence and development of HCC. Nonetheless, the mechanism through which Baicalin inhibits HCC growth and metastasis remain unknown. This work discovered that Baicalin inhibited HCC cell proliferation, invasion, metastasis while inducing cell cycle arrest at the G0/G1 phase and apoptosis. In vivo HCC xenograft results indicated that Baicalin inhibited HCC growth. Western blotting analysis indicated that Baicalin suppressed the expressions of ROCK1, p‐GSK‐3β, and β‐catenin, whereas it up‐regulated the expressions of GSK‐3β and p‐β‐catenin. Baicalin also reduced the expressions of Bcl‐2, C‐myc, Cyclin D1, MMP‐9, and VEGFA, while increasing the expression of Bax. Molecular docking revealed that Baicalin docked in the binding site of the ROCK1 agonist, with a binding energy of −9 kcal/mol between the two. In addition, lentivirus‐mediated suppression of ROCK1 expression improved the inhibitory effect of Baicalin on the proliferation, invasion, and metastasis of HCC and the expression of proteins associated with ROCK1/GSK‐3β/β‐catenin signaling pathway. Moreover, restoring ROCK1 expression decreased the anti‐HCC efficacy of Baicalin. These findings suggest that Baicalin may decrease HCC proliferation and metastasis by suppressing ROCK1/GSK‐3β/β‐catenin signaling. [ABSTRACT FROM AUTHOR]

The pituitary gland is a central regulator of reproduction, producing two gonadotropins, follicle‐stimulating hormone (Fsh) and luteinizing hormone (Lh), which regulate gonadal development, sex steroid synthesis, and gamete maturation. The present study sought to optimize an in vitro test system using pituitary cells isolated from previtellogenic female coho salmon and rainbow trout, focusing on fshb and lhb subunit gene expression. Initially, we optimized culture conditions for duration and benefits of culturing with and without addition of endogenous sex steroids (17β‐estradiol [E2] or 11‐ketotestosterone) or gonadotropin‐releasing hormone (GnRH). The results suggest that culturing with and without E2 was valuable because it could mimic the (+) feedback effects on Lh that are observed from in vivo studies. After optimizing assay conditions, a suite of 12 contaminants and other hormones was evaluated for their effects on fshb and lhb gene expression. Each chemical was tested at four to five different concentrations up to solubility limitations in cell culture media. The results indicate that more chemicals alter lhb synthesis than fshb. The more potent chemicals were estrogens (E2 and 17α‐ethynylestradiol) and the aromatizable androgen testosterone, which induced lhb. The estrogen antagonists 4‐OH‐tamoxifen and prochloraz decreased the E2‐stimulated expression of lhb. Among several selective serotonin reuptake inhibitors tested, the sertraline metabolite norsertraline was notable for both increasing fshb synthesis and decreasing the E2 stimulation of lhb. These results indicate that diverse types of chemicals can alter gonadotropin production in fish. Furthermore, we have shown that pituitary cell culture is useful for screening chemicals with potential endocrine‐disrupting activity and can support the development of quantitative adverse outcome pathways in fish. Environ Toxicol Chem 2023;42:1730–1742. © 2023 SETAC [ABSTRACT FROM AUTHOR]

White‐rot fungi efficiently degrade wood lignin; however, the mechanisms involved remain largely unknown. Recently, a forward genetics approach to identify several genes in Pleurotus ostreatus (Agaricales) in which mutations cause defects in wood lignin degradation was used. For example, pex1 encodes a peroxisome biogenesis factor and gat1 encodes a putative Agaricomycetes‐specific DNA‐binding transcription factor. In this study, we examined the effects of single‐gene mutations in pex1 or gat1 on wood lignin degradation in another white‐rot fungus, Gelatoporia (Ceriporiopsis) subvermispora (Polyporales), to investigate conserved and derived degradation mechanisms in white‐rot fungi. G. subvermispora pex1 and gat1 single‐gene mutant strains were generated from a monokaryotic wild‐type strain, FP‐90031‐Sp/1, using plasmid‐based CRISPR/Cas9. As in P. ostreatus, Gsgat1 mutants were nearly unable to degrade lignin sourced from beech wood sawdust medium (BWS), while Gspex1 mutants exhibited a delay in lignin degradation. We also found that the transcripts of lignin‐modifying enzyme‐encoding genes, mnp4, mnp5, mnp6, mnp7, and mnp11, which predominantly accumulate in FP‐90031‐Sp/1 cultured with BWS, were greatly downregulated in Gsgat1 mutants. Taken together, the results suggest that Gat1 may be a conserved regulator of the ligninolytic system of white‐rot fungi and that the contribution of peroxisomes to the ligninolytic system may differ among species. [ABSTRACT FROM AUTHOR]

Apristurus ovicorrugatus, a new species of deepwater catshark, is described from northwestern Australia. Unique egg cases belonging to an unknown species of Apristurus prompted a more detailed investigation of Apristurus specimens off northwestern Australia. One specimen previously identified as A. sinensis collected off Dampier Archipelago was found gravid with a single egg case. Removal of this egg case confirmed that this species was responsible for producing the unique egg cases previously recorded. The egg cases of this species have strong T‐shaped longitudinal ridges on the dorsal and ventral surfaces which are unique in the genus Apristurus. The ridges most closely resemble those present in Bythaelurus canescens from South America, but are larger and always T‐shaped. The holotype is closest morphologically to A. sinensis but differs in having a medium brown buccal cavity (vs. jet black), ridged egg cases (vs. smooth egg cases), fewer intestinal spiral valve turns and larger pectoral fins. The holotype is also similar, and closest on a molecular level, to A. nakayai with which it shares a unique synapomorphic character, the white shiny iris (apomorphic within the genus). A late‐term embryo removed from an egg case superficially resembled the holotype except in having two parallel rows of enlarged dermal denticles on the dorsolateral predorsal surface. Recent nomenclatural changes to the genera Apristurus and Pentanchus are discussed and challenged. This study highlights the important contribution that egg case morphology has on oviparous elasmobranch taxonomy. [ABSTRACT FROM AUTHOR]

Fungi and antifungal compounds are relevant to the United Nation's Sustainable Development Goals. However, the modes‐of‐action of antifungals—whether they are naturally occurring substances or anthropogenic fungicides—are often unknown or are misallocated in terms of their mechanistic category. Here, we consider the most effective approaches to identifying whether antifungal substances are cellular stressors, toxins/toxicants (that are target‐site‐specific), or have a hybrid mode‐of‐action as toxin–stressors (that induce cellular stress yet are target‐site‐specific). This newly described 'toxin–stressor' category includes some photosensitisers that target the cell membrane and, once activated by light or ultraviolet radiation, cause oxidative damage. We provide a glossary of terms and a diagrammatic representation of diverse types of stressors, toxic substances, and toxin–stressors, a classification that is pertinent to inhibitory substances not only for fungi but for all types of cellular life. A decision‐tree approach can also be used to help differentiate toxic substances from cellular stressors (Curr Opin Biotechnol 2015 33: 228–259). For compounds that target specific sites in the cell, we evaluate the relative merits of using metabolite analyses, chemical genetics, chemoproteomics, transcriptomics, and the target‐based drug‐discovery approach (based on that used in pharmaceutical research), focusing on both ascomycete models and the less‐studied basidiomycete fungi. Chemical genetic methods to elucidate modes‐of‐action currently have limited application for fungi where molecular tools are not yet available; we discuss ways to circumvent this bottleneck. We also discuss ecologically commonplace scenarios in which multiple substances act to limit the functionality of the fungal cell and a number of as‐yet‐unresolved questions about the modes‐of‐action of antifungal compounds pertaining to the Sustainable Development Goals. [ABSTRACT FROM AUTHOR]

The study of cerebellar development has been at the forefront of neuroscience since the pioneering work of Wilhelm His Sr., Santiago Ramón y Cajal and many others since the 19th century. They laid the foundation to identify the circuitry of the cerebellum, already revealing its stereotypic three‐layered cortex and discerning several of its neuronal components. Their work was fundamental in the acceptance of the neuron doctrine, which acknowledges the key role of individual neurons in forming the basic units of the nervous system. Increasing evidence shows that the cerebellum performs a variety of homeostatic and higher order neuronal functions beyond the mere control of motor behaviour. Over the last three decades, many studies have revealed the molecular machinery that regulates distinct aspects of cerebellar development, from the establishment of a cerebellar anlage in the posterior brain to the identification of cerebellar neuron diversity at the single cell level. In this review, we focus on summarizing our current knowledge on early cerebellar development with a particular emphasis on the molecular determinants that secure neuron specification and contribute to the diversity of cerebellar neurons. [ABSTRACT FROM AUTHOR]

The present study aims to evaluate the efficacy of an anti‐immunoglobulin E monoclonal antibody (omalizumab) in the treatment of allergic asthma (AS). A total of 34 patients with moderate‐to‐severe bronchial asthma admitted to the Respiratory Department of Tianjin First Central Hospital between September 2019 and September 2021 were enrolled in this study. The patients were treated with omalizumab in addition to conventional inhaled corticosteroids + long‐acting β2 agonist treatment. The therapeutic effects before and after the addition of omalizumab were compared. The lung function indicators (ratio of the forced expiratory volume [FEV] in the first second to the forced vital capacity, FEV in the first second, forced expiratory flow [FEF] at 50% of vital capacity, FEF at 75% of vital capacity, and maximum mid‐expiratory flow), fractionated exhaled nitric oxide values, asthma control test scores, rhinoconjunctivitis quality of life questionnaire scores, and urticaria control test scores were significantly different after 4 months of the regular administration of omalizumab (p < 0.05) compared with before administration. The use of omalizumab had a significant efficacy in the treatment of patients with AS, and the effects were obvious in the subgroups of patients with a combination of AS and atopic dermatitis, chronic urticaria, and allergic rhinitis. These results indicate that the treatment is worthy of clinical promotion. [ABSTRACT FROM AUTHOR]

The most common driver gene mutation in patients with non‐small‐cell lung cancer (NSCLC) is an epidermal growth factor receptor (EGFR) mutation. With the introduction of EGFR‐tyrosine kinase inhibitors, the treatment prospects and prognosis of NSCLC patients with EGFR‐sensitive mutations have significantly improved. Nonetheless, therapies targeting NSCLC are still associated with a risk of primary or secondary nonclassical drug resistance mutations. In recent years, the research and methodology have led to the continuous discovery of new drugs and drug resistance targets. These explorations have also resulted in continuously discovering new drugs. Consequently, rapid advancements have been made to overcome NSCLC drug resistance. This study aimed to review the current dilemma of targeted therapy for EGFR mutation‐positive NSCLC and the coping strategies for these difficulties. [ABSTRACT FROM AUTHOR]

Type I photodynamic therapy (PDT) represents a promising treatment modality for tumors with intrinsic hypoxia. However, type I photosensitizers (PSs), especially ones with near infrared (NIR) absorption, are limited and their efficacy needs improvement via new targeting tactics. We develop a NIR type I PS by engineering acridinium derived donor‐π‐acceptor systems. The PS exhibits an exclusive type I PDT mechanism due to effective intersystem crossing and disfavored energy transfer to O2, and shows selective binding to G‐quadruplexes (G4s) via hydrogen bonds identified by a molecular docking study. Moreover, it enables fluorogenic detection of G4s and efficient O2⋅− production in hypoxic conditions, leading to immunogenic cell death and substantial variations of gene expression in RNA sequencing. Our strategy demonstrates augmented antitumor immunity for effective ablation of immunogenic cold tumor, highlighting its potential of RNA‐targeted type I PDT in precision cancer therapy. [ABSTRACT FROM AUTHOR]

Aim: The clinical benefits associated with 5 years of endocrine therapy in the treatment of hormone receptor‐positive, early‐stage breast cancer (ESBC) have been well‐substantiated. However, numerous studies have reported on the results of extended (i.e., >5 years) endocrine therapy to further effectuate a clinical benefit, with varying outcomes. Hence, the purpose of this study is to review these prolonged investigations and endeavor to clarify their corresponding treatment implications. Methods: We reviewed the study findings from several randomized controlled trials and meta‐analyses, which incorporated clinical outcomes from pre‐and postmenopausal, hormone receptor‐positive, ESBC patients. Results: Hormone receptor‐positive, ESBC patients treated with 5 years of endocrine therapy, who are node‐negative with tumors <2 cm, will unlikely benefit from five additional years of treatment. Conversely, in women with larger tumors and node‐positive disease, 7–8 total years of endocrine therapy may be indicated. Ultimately, clinicians should also consider the attendant side effects from endocrine therapy, namely bone fractures, namely cardiovascular symptoms, and vasomotor symptoms, when considering the appropriate treatment regimen. Conclusions: While increased duration of endocrine therapy may selectively accord significant clinical benefits, prior to determining the patient's treatment interval, physicians should also assess the cumulative side effects from endocrine therapy when endeavoring to maintain treatment compliance and bolster quality of life. [ABSTRACT FROM AUTHOR]

In this study, Raman spectroscopy is used to characterize different formulations of active pharmaceutical ingredient (API) of Lornoxicam, a nonsteroidal anti‐inflammatory drug for qualitative and quantitative analyses. The Raman spectral characteristic peaks associated with API and excipients are identified, which increase or decrease as their concentrations change in different formulations. The spectral response was analyzed qualitatively and quantitatively by using chemometrics tools such as principal component analysis (PCA) model and partial least squares regression (PLSR) analysis model, respectively. The characteristic Raman spectral features associated with the different formulations of API of Lornoxicam were used to differentiate different groups of Raman spectral data using PCA. By using PLSR model, root mean square error of cross validation (RMSECV) was found to be 0.76 mg during the development of prediction model and according to the (R2) value, the goodness of the model was found to be 0.99. Furthermore, the concentration of API in the blind sample was measured. In comparison to the 15/35 mg (w/w), this concentration was projected to be 14.13/35 mg (w/w). Raman spectroscopy along with PCA and PLSR analyses is a useful tool for determining the concentration of Lornoxicam in pharmaceutical samples, both qualitatively and quantitatively. [ABSTRACT FROM AUTHOR]

Accurate burn depth assessment is crucial to determine treatment plans for burn patients. We have previously proposed a method for performing burn depth assessments based on photoacoustic (PA) imaging, and we have demonstrated the validity of this method, which allows the successful detection of PA signals originating from the blood under the bloodless burned tissue, using rat burn models. Based on these findings, we started a clinical study in which we faced two technical issues: (1) When the burn depth was shallow, PA signals due to skin contamination and/or melanin in the epidermis (surface signals) could not be distinguished from PA signals originating from the blood in the dermis; (2) the size of the system was too large. To solve these issues, we propose a burn depth diagnosis based on dual‐wavelength light emitting diodes (LEDs)‐excited PA imaging. The use of LEDs rendered the system compact compared to the previous one that used a conventional solid‐state laser. We replicated human burned skin by applying a titrated synthetic melanin solution onto the wound surface in albino rat burn models and measured their burn depths by PA excitation at 690 and 850 nm, where melanin and haemoglobin show greatly different absorption coefficients. As a result, the surface signals were eliminated by subtracting the PA signals at 690 nm from those at 850 nm. The resultant estimated burn depths were strongly correlated with the histological assessment results. The validity of the proposed method was also examined using a burn model of rats with real melanin. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic chronic rhinosinusitis is an often treatment‐resistant inflammatory disease mediated by type‐2 cytokines, including interleukin (IL)‐5. Mepolizumab, a monoclonal antibody drug targeting IL‐5, has demonstrated efficacy and safety in inflammatory airway disease, but there is negligible evidence on direct tissue response. The study's aim was to determine the local effect of mepolizumab on inflammatory biomarkers in sinonasal tissue of eosinophilic chronic rhinosinusitis patients. Methods: Adult patients with eosinophilic chronic rhinosinusitis received 100mg mepolizumab subcutaneously at four‐weekly intervals for 24 weeks in this prospective phase 2 clinical trial. Tissue eosinophil counts, eosinophil degranulation (assessed as submucosal eosinophil peroxidase deposition by immunohistochemistry) and cytokine levels (measured in homogenates by immunoassay) were evaluated in ethmoid sinus tissue biopsies collected at baseline and at weeks 4, 8, 16 and 24. Results: Twenty patients (47.7 ± 11.7 years, 50% female) were included. Sinonasal tissue eosinophil counts decreased after 24 weeks of treatment with mepolizumab (101.64 ± 93.80 vs 41.74 ± 53.76 cells per 0.1 mm2; p =.035), eosinophil degranulation remained unchanged (5.79 ± 2.08 vs 6.07 ± 1.20, p =.662), and type‐2 cytokine levels increased in sinonasal tissue for IL‐5 (10.84 ± 18.65 vs 63.98 ± 50.66, p =.001), IL‐4 (4.48 ± 3.77 vs 9.38 ± 7.56, p =.004), IL‐13 (4.02 ± 2.57 vs 6.46 ± 3.99, p =.024) and GM‐CSF (1.51 ± 1.74 vs 4.50 ± 2.97, p =.001). Conclusion: Mepolizumab reduced eosinophils in sinonasal tissue, demonstrating that antagonism of IL‐5 suppresses eosinophil trafficking. With reduced tissue eosinophils, a local type‐2 inflammatory feedback loop may occur. The study exposes mechanistic factors which may explain incomplete treatment response. [ABSTRACT FROM AUTHOR]

The medicinal mushroom Cordyceps militaris contains abundant valuable bioactive ingredients that have attracted a great deal of attention in the pharmaceutical and cosmetic industries. However, the development of this valuable mushroom faces the obstacle of lacking powerful genomic engineering tools. Here, by excavating the endogenous tRNA‐processed element, introducing the extrachromosomal plasmid and alongside with homologous template, we develop a marker‐free CRISPR‐Cas9‐TRAMA genomic editing system to achieve the multiplex gene precise editing and large synthetic cluster deletion in C. militaris. We further operated editing in the synthetases of cordycepin and ergothioneine to demonstrate the application of Cas9‐TRAMA system in protein modification, promoter strength evaluation and 10 kb metabolic synthetic cluster deletion. The Cas9‐TRAMA system provides a scalable method for excavating the valuable metabolic resource of medicinal mushrooms and constructing a mystical cellular pathway to elucidate the complex cell behaviours of the edible mushroom. [ABSTRACT FROM AUTHOR]

Metabolic rate depression during prolonged bouts of torpor is characteristic of mammalian hibernation, reducing energy expenditures over the winter. Cell cycle arrest is observed in quiescent cells during dormancy, partly due to the retinoblastoma (Rb) protein at G1/S, given cell division and proliferation are metabolic‐costly processes. Rb binds to E2F transcription factors and recruits corepressors (e.g., SUV39H1) to E2F target genes, blocking their transcription and cell cycle passage. Phosphorylation by cyclin‐CDK complexes at S780 or S795 abolishes Rb‐mediated repression, allowing transition into S phase. The present study compares Rb‐E2F1 responses between euthermic and torpid states in five organs (brain, heart, kidney, liver, skeletal muscle) of 13‐lined ground squirrels (Ictidomys tridecemlineatus). Immunoblotting assessed the expression of Rb, pRb (S780, S795), E2F1, and SUV39H1. Our findings demonstrate multi‐tissue upregulation of Rb and SUV39H1 during torpor, with tissue‐specific changes to E2F1 and pRb (S780), suggesting Rb‐E2F1 contributes to cell cycle control in hibernation. Highlights: Tissue‐specific regulation of the Rb‐E2F1 pathway in 13‐lined ground squirrel.Rb repress E2F1, and Suv39H1 can act as additional factor in cell cycle repression in brain, kidney and liver.Possibility of alternate of roles of E2F1 in the heart and liver during hibernation. [ABSTRACT FROM AUTHOR]

Photosensitizers that gather high photo‐oxidizing power and strong visible‐light absorption are of great interest in the development of new photo‐chemotherapeutics. Indeed, such compounds constitute attractive candidates for the design of type I photosensitizers that are not dependent on the presence of oxygen. In this paper, we report on the synthesis and studies of new ruthenium(II) complexes that display strong visible‐light absorption and can oxidize guanine residues under visible‐light irradiation, as evidenced by nanosecond transient absorption spectroscopy. The reported compounds also tightly bind to G‐quadruplex DNA structures from the human telomeric sequence (TTAGGG repeat). The kinetic and thermodynamic parameters of the interaction of these Ru(II) complexes with G‐quadruplex and duplex DNA were studied thanks to luminescence titrations and bio‐layer interferometry measurements, which revealed higher affinities towards the non‐canonical G‐quadruplex architecture. Docking experiments and non‐covalent ionic analysis allowed us to gain information on the mode and the strength of the interaction of the compounds towards G‐quadruplex and duplex DNA. The different studies emphasize the substantial influence of the position and the number of non‐chelating nitrogen atoms on the interaction with both types of DNA secondary structures. [ABSTRACT FROM AUTHOR]

Vertebrate pancreas organogenesis is a stepwise process regulated by a complex network of signaling and transcriptional events, progressively steering the early endoderm toward pancreatic fate. Many crucial players of this process have been identified, including signaling pathways, cis‐regulatory elements, and transcription factors (TFs). Pancreas‐associated transcription factor 1a (PTF1A) is one such TF, crucial for pancreas development. PTF1A mutations result in dramatic pancreatic phenotypes associated with severe complications, such as neonatal diabetes and impaired food digestion due to exocrine pancreatic insufficiency. Here, we present a brief overview of vertebrate pancreas development, centered on Ptf1a function and transcriptional regulation, covering similarities and divergences in three broadly studied organisms: human, mouse and zebrafish. [ABSTRACT FROM AUTHOR]

Agenesis of Corpus Callosum, Cardiac, Ocular, and Genital Syndrome (ACOGS; OMIM #618929) is a rare genetic disorder characterized by global developmental delay, agenesis or hypoplasia of corpus callosum, craniofacial dysmorphism, ocular, cardiac, and genital anomalies. ACOGS is caused by variations in the CDH2 gene. Our patient had a novel finding besides the classical findings of ACOGS. To the best of our knowledge, only 14 patients with ACOGS have been reported. Here, we reported the fifteenth patient with ACOGS, having a novel de novo nonsense variant in the CDH2 gene, and the first patient from Turkey with a novel finding. Our patient was the first female to have a renal anomaly since only genital malformations were reported in male patients (cryptorchidism, micropenis) so far. [ABSTRACT FROM AUTHOR]

Introduction. The molecular classification of breast cancer (BC) based on gene expression and then protein profile has made it possible to distinguish different molecular subtypes. The objective of this study was to describe immunohistochemical features of BC infiltrating women at the Nganda Hospital Center in Kinshasa, Democratic Republic of the Congo (DRC). Methods. A retrospective study from 2014 to 2019 involved 190 patients with invasive BC who were enrolled at the Nganda Hospital Center. The tumors were analyzed histologically and classified after an immunohistochemical study into subtypes: luminal A, luminal B, HER2-overexpressed, and triple-negative. A chi-square test was performed to assess the relationship between age, histological grade, and these subtypes. Results. The luminal A subtype (44.74%) was the most common, followed by luminal B (40.53%), triple-negative (10.53%), and HER2-overexpressed (4.20%). The mean age of the patients at diagnosis was 48.27 years. Of all cases, 94.21% were ductal, 2.63% were mucinous, and 2.11% were lobular. They were classified as grade I in 68.82% of the cases, grade II in 28.42% of the cases, and grade III in 3.16% of the cases. There was a significant association between histological grade and breast cancer subtypes (p < 0.0001), but no correlation was found with age (p = 0.467). Conclusion. In our BC patients, the luminal A was predominant, while HER2-overexpressed was the least found. A strong association was noted between histological grade and molecular subtypes. These results should allow for important clinical and policy implications for BC control in the DRC. [ABSTRACT FROM AUTHOR]

This study aimed to determine the apoptosis and autophagy‐inducing mechanism of atractylodin in human breast cancer MCF‐7 cells. The molecular mechanism of anticancer activity of atractylodin was confirmed by assessing the levels of reactive oxygen species (ROS) level, lipid peroxidation (LPO), antioxidants activity, dual staining, and comet assay. Moreover, cleaved caspases 3, 8, and 9, and signaling proteins, such as p53, Bcl‐2, and Bax, phosphatidylinositol‐3‐kinase/protein kinase B/mammalian target of rapamycin(P13K/Akt/mTOR), LC3I and LC3II, and beclin‐1 were analyzed. In MCF‐7 cells treated with atractylodin, the concentration‐dependent toxicity, increased LPO, increased production of ROS, and decreased activity of superoxide dismutase, catalase, and glutathione peroxidasewere observed. In MCF‐7 cells, atractylodin administration decreased Bcl‐2 expression while activating the expression of p53, Bax, cleaved caspase‐3, caspase‐8, and caspase‐9 apoptotic members. Furthermore, atractylodin blocked the P13K/Akt/mTOR signaling pathway, increased the conversion of LC3I to its lipidated form of LC3II, and increased beclin‐1 expression, whereas downregulated the p62 expression in MCF‐7 cells. As a result, altering apoptotic and autophagy‐related biomarkers, atractylodin triggered apoptosis and autophagy in MCF‐7 cells. As a result, atractylodin could be utilized to treat human breast cancer after the proper clinical trial. [ABSTRACT FROM AUTHOR]

Allergic rhinitis is a global illness that puzzles many researchers. Most patients with allergic rhinitis also have lower airway hyperresponsiveness, and an allergic rhinitis attack can increase lower airway hyperresponsiveness. However, the mechanism of the effect of allergic rhinitis on the lower airways is still unclear. In this paper, the effects of allergic rhinitis on the lower airways are studied in terms of epidemiology, anatomy, pathophysiology, nasal function loss, inflammation drainage, nasobronchial reflex, and whole-body circulatory flow to determine the mechanism involved and provide ideas for future diagnosis, treatment, and experiments. [ABSTRACT FROM AUTHOR]

Diverse neurons in the parabrachial nucleus (PB) communicate with widespread brain regions. Despite evidence linking them to a variety of homeostatic functions, it remains difficult to determine which PB neurons influence which functions because their subpopulations intermingle extensively. An improved framework for identifying these intermingled subpopulations would help advance our understanding of neural circuit functions linked to this region. Here, we present the foundation of a developmental‐genetic ontology that classifies PB neurons based on their intrinsic, molecular features. By combining transcription factor labeling with Cre fate‐mapping, we find that the PB is a blend of two, developmentally distinct macropopulations of glutamatergic neurons. Neurons in the first macropopulation express Lmx1b (and, to a lesser extent, Lmx1a) and are mutually exclusive with those in a second macropopulation, which derive from precursors expressing Atoh1. This second, Atoh1‐derived macropopulation includes many Foxp2‐expressing neurons, but Foxp2 also identifies a subset of Lmx1b‐expressing neurons in the Kölliker–Fuse nucleus (KF) and a population of GABAergic neurons ventrolateral to the PB ("caudal KF"). Immediately ventral to the PB, Phox2b‐expressing glutamatergic neurons (some coexpressing Lmx1b) occupy the KF, supratrigeminal nucleus, and reticular formation. We show that this molecular framework organizes subsidiary patterns of adult gene expression (including Satb2, Calca, Grp, and Pdyn) and predicts output projections to the amygdala (Lmx1b), hypothalamus (Atoh1), and hindbrain (Phox2b/Lmx1b). Using this molecular ontology to organize, interpret, and communicate PB‐related information could accelerate the translation of experimental findings from animal models to human patients. [ABSTRACT FROM AUTHOR]

In the wild, the light/temperature environment cyclically oscillates insofar as the temperature rises after dawn and drops after dusk. In the underwater photo‐environment, light is filtered through the water column so that blue photons reach greater depths. This paper investigates the combined effects of both factors with two temperature regimes (constant temperature = 26°C, CTE vs. daily thermocycle = 28°C day:24°C night, TC) and three light wavelengths (white‐W, blue‐B, red‐R) on Danio rerio embryos and larvae from fertilization to 30 days post‐fertilization (dpf). It studied hatching rate, larval survival, growth, and food intake (gut content). It analyzed the expression of the genes involved in stress (crh), somatic growth (gh, ifg1a, igf2a), and food intake control (npy, agrp, ghrelin, orexin, mch1, mch2, grp, cck8) at 10 and 30 dpf. The results revealed that the lowest hatching rate was in R regardless of the temperature regime. The highest growth rate was for the larvae reared with B + TC, which was consistent with the highest expression values of the growth factors. The highest feeding and expression levels of the genes involved in food intake were for the larvae in B (regardless of the temperature regime) and W + TC. Conversely, the R + CTE combination obtained the worst growth and feeding results. These findings indicate that the best larval performance can be achieved with combinations of blue wavelengths and cyclic temperature regimes that come closer to those in the natural environment. These results should be considered when optimizing rearing protocols to improve the growth and welfare of the fish larvae. Highlights: The most favorable combination for survival and growth was blue light with daily thermocycles.The worst development is observed under red light with constant temperature.Blue light and daily thermocycles stimulated food intake and growth factors. [ABSTRACT FROM AUTHOR]

The microbiome corresponds to the genetic component of microorganisms (archaea, bacteria, phages, viruses, fungi, and protozoa) that coexist with an individual. During the last two decades, research on this topic has become massive demonstrating that in both homeostasis and disease, the microbiome plays an important role, and in some cases, a decisive one. To date, microbiota have been identified at different body locations, such as the eyes, lung, gastrointestinal and genitourinary tracts, and skin, and technological advances have permitted the taxonomic characterization of resident species and their metabolites, in addition to the cellular and molecular components of the host that maintain a crosstalk with local microorganisms. Here, we summarize recent studies regarding microbiota residing in different zones of the body and their relationship with the immune system. We emphasize the immune components underlying pathological conditions and how they interact with local (and distant) microbiota. [ABSTRACT FROM AUTHOR]