GABAergic neurons in the ventral lateral geniculate nucleus and intergeniculate leaflet are involved in itch processing in mice.

Itch and pain are two closely related sensations that receiving similar encodings at multiple levels. Accumulated evidences suggest that activation of the ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL)-to-lateral and ventrolateral periaqueductal gray (l/vlPAG) projections mediates the antinociceptive effects of bright light therapy. Clinical study showed that bright light therapy may ameliorate cholestasis-induced pruritus. However, the underlying mechanism and whether this circuit participates in itch modulation remains unclear. In this study, chloroquine and histamine were utilized to induce acute itch models in mice. Neuronal activities in vLGN/IGL nucleus were evaluated with c-fos immunostaining as well as fiber photometry. Optogenetic manipulations were performed to activate or inhibit GABAergic neurons in the vLGN/IGL nucleus. Our results showed that the expressions of c-fos in vLGN/IGL were significantly increased upon both chloroquine- and histamine-induced acute itch stimuli. GABAergic neurons in vLGN/IGL were activated during histamine and chloroquine-induced scratching. Optogenetic activation of the vLGN/IGL GABAergic neurons exerts antipruritic effect, while inhibiting these neurons exerts pruritic effect. Our results provide evidence that GABAergic neurons in vLGN/IGL nucleus might play a crucial role in modulating itch, which may provide clue for application of bright light as an antipruritic treatment in clinic.

Effect of dietary patterns on dental caries among 12-15 years-old adolescents: a cross-sectional survey.

BACKGROUND: Several factors can influence the risk of dental caries, among which dietary factors have a significance impact on the occurrence of dental caries. The limitation of current studies is that they only focus on the influence of individual foods on the risk of dental caries. This study use cluster analysis to examine the relationship between dietary patterns and dental caries experience among adolescents aged 12-15. METHODS: Based on data from the first oral epidemic survey in Shanxi Province, a cross-sectional study was conducted among 11,351 adolescents aged 12-15 in Shanxi Province through oral examination and questionnaires. The questionnaire included the intake frequency of seven types of food. Descriptive statistics, cluster analysis, and multinomial logistic regression were used to analyze the association between dietary patterns and dental caries experience. RESULTS: The prevalence rate of caries was 44.57% and the mean DMFT score was 0.98 ± 1.49 in adolescents aged 12-15 in Shanxi Province. The caries rate was higher in females than males (X2 = 103.59, P < 0.001). Adolescents who grow up in one-child families have a lower caries risk than those who grow up in families with more than one child (OR:0.91; 95%CI:0.84-0.97). The dietary patterns of adolescents aged 12-15 can be divided into eight types, among which refreshments-rich diet (OR:1.47; 95%CI,1.22-1.77) can increase the risk of caries, while the coarse-grains-rich dietery pattern (OR:0.90; 95%CI, 0.79-0.97) has a lower caries risk. CONCLUSIONS: Social determinants of health such as sex, family size and dietary patterns influence the risk of dental caries. Certain dietary patterns could increase or decrease the risk of caries. The government, school canteens and news media should take dietary pattern factors seriously.

Glucoraphanin and sulforaphane biosynthesis by melatonin mediating nitric oxide in hairy roots of broccoli (Brassica oleracea L. var. italica Planch): insights from transcriptome data.

Glucoraphanin (GRA) is present in the seeds and nutrient organs of broccoli and is the precursor of the anti-cancer compound sulforaphane (SF). The hairy roots obtained by infecting broccoli (Brassica oleracea L. var. Italic Planch) leaves with Agrobacterium rhizogenes (ATCC15834) are phytohormonally autonomous, genetically stable, and can produce large amounts of the anti-cancer substance SF. Melatonin (MT) is a natural hormone widely found in plants. Studies have shown that melatonin can regulate the synthesis of secondary metabolites of downstream targets by mediating the synthesis of signal molecules. However, whether MT regulates the synthesis of NO and H2O2 and mediates the synthesis mechanism of secondary metabolites, GRA and SF, is not yet clear. In this study, the hairy roots of broccoli were treated with 500 µmol/L MT, and the genome of broccoli (Brassica oleracea L. var. botrytis L) was used as the reference genome for transcriptome analysis. By this approach, we found that MT regulates the synthesis of NO and H2O2 and mediates the synthesis of secondary metabolites GRA and SF. GO annotations indicated that DEGs involved in the MT treatment of broccoli hairy roots were mainly related to catalytic activity, cells, and metabolic processes; the KEGG pathway analysis indicated that MT treatment likely affects the hormone signal transduction process in broccoli hairy roots; broccoli hairy roots were treated with 500 µmol/L MT for 0, 6, 12, 20, and 32 h, respectively; compared with 0 h, the yield of GRA and SF increased under the other treatments. The highest yields of GRA and SF occurred at 12 h. The NO content was the highest at 12 h, and the H2O2 content was positively correlated with MT concentration. The content of NO and H2O2 were regulated, and the content of GRA and SF was increased under MT treatment. NO synthase inhibitor (L-NAME and TUN) could effectively inhibit the content of NO in broccoli hairy roots and reduce GRA and SF yield; MT could regulate NO levels by regulating NO synthesis-related enzymes and could alleviate the reduction of NO content in tissue cells caused by NO synthase inhibitor and promote NO synthesis. These results have important theoretical implications for understanding the regulation of GRA and SF synthesis events by NO and H2O2.

Transmembrane transport process and endoplasmic reticulum function facilitate the role of gene cel1b in cellulase production of Trichoderma reesei.

BACKGROUND: A total of 11 ß-glucosidases are predicted in the genome of Trichoderma reesei, which are of great importance for regulating cellulase biosynthesis. Nevertheless, the relevant function and regulation mechanism of each ß-glucosidase remained unknown. RESULTS: We evidenced that overexpression of cel1b dramatically decreased cellulase synthesis in T. reesei RUT-C30 both at the protein level and the mRNA level. In contrast, the deletion of cel1b did not noticeably affect cellulase production. Protein CEL1B was identified to be intracellular, being located in vacuole and cell membrane. The overexpression of cel1b reduced the intracellular pNPGase activity and intracellular/extracellular glucose concentration without inducing carbon catabolite repression. On the other hand, RNA-sequencing analysis showed the transmembrane transport process and endoplasmic reticulum function were affected noticeably by overexpressing cel1b. In particular, some important sugar transporters were notably downregulated, leading to a compromised cellular uptake of sugars including glucose and cellobiose. CONCLUSIONS: Our data suggests that the cellulase inhibition by cel1b overexpression was not due to the ß-glucosidase activity, but probably the dysfunction of the cellular transport process (particularly sugar transport) and endoplasmic reticulum (ER). These findings advance the knowledge of regulation mechanism of cellulase synthesis in filamentous fungi, which is the basis for rationally engineering T. reesei strains to improve cellulase production in industry.

Transcriptome analysis of genes related to glucoraphanin and sulforaphane synthesis in methyl jasmonate treated broccoli (Brassica oleracea var. italica) hairy roots.

Hairy roots obtained by infecting broccoli (Brassica oleracea var. italica) leaves with Agrobacterium rhizogenes (ATCC15834) have the characteristics of phytohormone autonomy, genetic stability and can produce a large amount of the anti-cancer substance Sulforaphane (SF) and the biosynthetic precursor Glucoraphanin (GRA). Under the induction of the exogenous signaling molecule methyl jasmonate (MeJA), the production of SF in broccoli hairy roots was significantly increased. However, the molecular mechanism of GRA and SF synthesis in hairy roots of broccoli treated with MeJA has not been reported. In this study, according to the yield of GRA and SF, the best concentration of MeJA treatment for hairy roots of broccoli was selected. After 18 days of growth, broccoli hairy roots were treated with 10 mmol L-1 MeJA for 0, 3, 6, 9 and 12 h. Compared with 0 h, the yield of GRA and SF increased under other treatments. The highest yield of GRA and SF occurred at 9 h, which were 2.22-fold and 1.74-fold higher than those at 0 h. Brassica oleracea var. botrytis was used as reference genome, and 5,757 differentially expressed genes (DEG) were observed at 0, 3, 6, 9 and 12 h under 10 mmol L-1 MeJA treatment, of which 4,673 were down-regulated and 1084 were up-regulated. The key genes regulating GRA synthesis, CYP79F1, CYP83A1, UGT74B1, FMOGS-OX5 and GSL-OH, were up-regulated at 0 and 3 h, and down-regulated the rest of the time; BCAT2 was up-regulated at 6, 9, 12 h, and at 0, 3 h expression was down-regulated, transcription factors MYB28 and MYB29 were down-regulated by exogenous MeJA treatment. A pathway of GRA biosynthesis and transformation pathways in MeJA-treated broccoli hairy roots was simulated and the molecular mechanism of GRA biosynthesis and SF accumulation in broccoli hairy roots under MeJA treatment was revealed.

Thick Two-Dimensional Water Film Confined between the Atomically Thin Mica Nanosheet and Hydrophilic Substrate.

The interesting properties of water molecules confined in a two-dimensional (2D) environment have aroused great attention. However, the study of 2D-confined water at the hydrophilic-hydrophilic interface is largely unexplored due to the lack of appropriate system. In this work, the behavior of water molecules confined between an atomically thin mica nanosheet and a hydrophilic SiO2/Si substrate was investigated using an atomic force microscope in detail at ambient conditions. The confined water molecules aggregated as droplets when the relative humidity (RH) of the environment was 11%. A large-area 2D water film with a uniform thickness of ∼2 nm was observed when the mica flake was incubated at 33% RH for 1 h before being mechanically exfoliated on a SiO2/Si substrate. Interestingly, the water film showed ordered edges with a predominant angle of 120°, which was the same with the lattice orientation of the mica nanosheet on top of it. The water film showed a fluidic behavior at the early stage and reached a stable state after 48 h under ambient conditions. The surface properties of the upper mica nanosheet and the underlying substrate played a crucial role in manipulating the behavior of confined water molecules. When the surface of the upper mica nanosheet was modified by Na+, Ni2+, and aminopropyltriethoxysilane (APS), only some small water droplets were observed instead of a water film. The surface of the underlying SiO2/Si substrate was functionalized by hydrophilic APS and hydrophobic octadecyltrimethoxysiliane (OTS). The small water droplets were imaged on a hydrophobic OTS-SiO2/Si substrate, while the water film with regular edges was maintained on a hydrophilic APS-SiO2/Si substrate. Our results might provide an alternative molecular view for investigating structures and properties of confined water molecules in 2D environments.

Optical thickness identification of transition metal dichalcogenide nanosheets on transparent substrates.

Transparent and flexible devices based on two-dimensional (2D) materials hold great potential for many electronic/optoelectronic applications. The direct and fast thickness identification of 2D materials on transparent substrates is therefore an essential step in such applications, but remains challenging. Here, we present a simple, rapid and reliable optical method to identify the thickness of 2D nanosheets on transparent substrates, such as polydimethylsiloxane, glass, and coverslip. Under reflection and transmission light, 1-20L MoS2 and 1-14L WSe2 nanosheets can be reliably identified by measuring the optical contrast difference between the 2D nanosheets and substrates in color, red, green or blue channels. Meanwhile, the values of all the measured contrast differences as a function of layer number can be well fitted with the Boltzmann function, indicating the generalizability and reliability of our optical method. Our method will not only facilitate the fundamental study of the thickness-dependent properties of 2D nanosheets, but will also expand their potential applications in the field of flexible/transparent electronics and optoelectronics.

Zn or O? An Atomic Level Comparison on Antibacterial Activities of Zinc Oxides.

For the first time, the influence of different types of atoms (Zn and O) on the antibacterial activities of nanosized ZnO was quantitatively evaluated with the aid of a 3D-printing-manufactured evaluation system. Two different outermost atomic layers were manufactured separately by using an ALD (atomic layer deposition) method. Interestingly, we found that each outermost atomic layer exhibited certain differences against gram-positive or gram-negative bacterial species. Zinc atoms as outermost layer (ZnO-Zn) showed a more pronounced antibacterial effect towards gram-negative E. coli (Escherichia coli), whereas oxygen atoms (ZnO-O) showed a stronger antibacterial activity against gram-positive S. aureus (Staphylococcus aureus). A possible antibacterial mechanism has been comprehensively discussed from different perspectives, including Zn(2+) concentrations, oxygen vacancies, photocatalytic activities and the DNA structural characteristics of different bacterial species.

Bibliometric analysis of research trends and hotspots on robot-assisted thyroid surgery.

BACKGROUND: Thyroid surgery involves the partial or complete removal of the thyroid gland and is a frequently performed surgical procedure. The adoption of robots, equipped with flexible and stable operating systems, has garnered acceptance among numerous surgeons for their capability to enable precise anatomical dissection in thyroid surgery. To gain a comprehensive insight into the present research landscape of robot-assisted thyroid surgery, this paper endeavored to conduct a thorough analysis of the field through bibliometric analysis. METHODS: Relevant literature pertaining to robot-assisted thyroid surgery was retrieved from the Web of Science Core Collection (WOSCC) database, spanning from the inception of WOSCC to October 17, 2022. Visual analyses of publication quantity, distribution across countries/regions, institutions/organizations, authorship, journals, references, and keywords were conducted using Microsoft Excel, the bibliometrix package in R, Citescape, and VOSviewer software. RESULTS: A total of 505 articles from 406 institutions in 36 countries/regions were included. South Korea emerged with highest number of publications. Notably, Professor CHUNG WY from Yonsei University in South Korea and the journal "Surg Endosc" stood out with the most publications. The current research landscape indicated significant interest in endoscopic thyroidectomy, surgical procedures, and the axillary approach. In addition, transoral robotic thyroidectomy (TROT), and learning curve (LC) were recognized as research frontiers, representing potential future hotspots in this field. CONCLUSION: This study marks the first bibliometric analysis of the literature on robot-assisted thyroid surgery. The results highlight endoscopic thyroidectomy, surgical procedures, and the axillary approach as current research hotspots, with TROT and LC identified as potential future research hotspots.

The Safety and Efficacy of Remimazolam Compared to Dexmedetomidine for Awake Tracheal Intubation by Flexible Bronchoscopy: A Randomized, Double-Blind, Controlled Trial.

Background: Remimazolam is a novel ultra-short-acting benzodiazepine sedative that has the potential to be an alternative for procedural sedation due to its rapid sedation and recovery, no accumulation effect, stable hemodynamics, minimal respiratory depression, anterograde amnesia effect, and specific antagonist. Here, we aimed to compare the safety and efficacy of remimazolam with dexmedetomidine for awake tracheal intubation by flexible bronchoscopy (ATI-FB). Methods: Ninety patients scheduled for ATI-FB were randomly divided into three groups, each consisting of 30 cases: dexmedetomidine 0.6 µg/kg + sufentanil (group DS), remimazolam 0.073 mg/kg + sufentanil (group R1S), or remimazolam 0.093 mg/kg + sufentanil (group R2S). The primary outcome was the success rate of sedation. Secondary outcomes were MOAA/S scores, hemodynamic and respiratory parameters, intubation conditions, intubation time, tracheal intubation amnesia, and adverse events. Results: The success rates of sedation in groups R2S and DS were higher than that in group R1S (93.3%, 86.7%, respectively, vs 58.6%; P = 0.002), and intubation conditions were better than those in group R1S (P < 0.05). Group R2S had shorter intubation times than groups R1S and DS (P = 0.003), and a higher incidence of tracheal intubation amnesia than group DS (P = 0.006). No patient in the three groups developed hypoxemia or hypotension, and there were no significant differences in oligopnea, PetCO2, or bradycardia (P > 0.05). Conclusion: In conclusion, both DS and R2S had higher success rates of sedation, better intubation conditions, and minor respiratory depression, but R2S, with its shorter intubation time, higher incidence of anterograde amnesia, and ability to be antagonized by specific antagonists, may be a good alternative sedation regimen for patients undergoing ATI-FB.

Erdheim­Chester disease of multisystem involvement with delayed diagnosis: A case report and literature review.

Erdheim-Chester disease (ECD) is a rare tumor of histiocytic origin, characterized by foamy or lipid-laden histiocytes mixed or surrounded by fibrosis that infiltrate multiple organs. Misdiagnosis is common due to the diversity of clinical presentations. The present study reported a case of ECD with the involvements of bone, cardiac, aorta and retroperitoneum. The patient had no obvious clinical symptoms and no noteworthy foamy histiocytes or Touton giant cells were found on pathological examination, delaying the diagnosis. The patient was a young male found to have pericardial effusion on physical examination, and computed tomography (CT) revealed soft tissue infiltrates in the retroperitoneum and around the aorta. A mediastinal biopsy revealed fibrous connective tissue with small-vessel hyperplasia and acute-chronic inflammatory cell infiltration. The initial diagnosis was retroperitoneal fibrosis (RPF), and hormonal and tamoxifen treatments were administered. The patient presented with oliguria, eyelid edema and fever four years later. A repeat CT revealed an increase in the extent of tissue infiltration and pericardial effusion compared with the previous CT. Subsequent cardiac magnetic resonance imaging revealed massive thickening in the form of fibrotic tissue infiltrating the heart and surrounding thoracic and abdominal aorta. Single photon emission CT revealed multiple areas of increased bone metabolism, particularly symmetrical involvement of the long bones of both lower extremities. A biopsy of the perirenal tissue revealed fibrous tissue and a small number of lymphocytes and macrophages [typical foamy histiocytes observed via x200 magnification and hematoxylin-eosin (HE) staining, no presence of xanthogranuloma or Touton giant cells]. After a comprehensive evaluation and ruling out other diseases, the diagnosis of ECD was determined. The prognosis of this disease is poor; early diagnosis is critical and requires accurate judgment by clinicians. Biopsies of all involved sites and refinement of genetic tests to guide treatment, if possible, are both necessary.

Expression of FAP in Oral Leukoplakia and Oral Squamous Cell Carcinoma.

OBJECTIVE: This study aimed to investigate the potential of fibroblast activation protein (FAP) as a biomarker in the progression of oral leukoplakia (OLK) carcinogenesis. This was achieved by evaluating FAP expression at different levels of the organisation, namely oral normal mucosa (NM), OLK, and oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Altogether, 88 paraffin-embedded tissue samples were examined, including 55 cases of OLK, 13 cases of OSCC, and 20 cases of NM (control group). An exhaustive investigation was performed to examine FAP expression in NM, OLK, and OSCC tissues via immunohistochemistry (IHC). The relationship between FAP expression and clinical pathologic characteristics was analysed. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot (WB) also proved the expression of FAP in NM, OLK, and OSCC cells. Aberrant FAP expression in OLK and OSCC was explored using in vitro experiments. RESULTS: Immunohistochemical results showed that high FAP expression was significantly correlated with histopathologic grade (P = .038) but not correlated with age, sex, or region (P = .953, .622, and .108, respectively). The expression level of FAP in NM tissues (0.15 ± 0.01) was minimal, whereas it was observed in OLK (0.28 ± 0.04) and OSCC (0.39 ± 0.02) tissues with a noticeable increase in expression levels (P < .001). The expression level of FAP in OLK with severe abnormal hyperplasia (S-OLK) tissues (0.33 ± 0.04) was significantly higher than in OLK with mild abnormal hyperplasia (MI-OLK, 0.26 ± 0.02) and OLK with moderate abnormal hyperplasia (MO-OLK, 0.28 ± 0.03) tissues (P < .001 and P = .039, respectively). The results of RT-PCR illustrated that the relative expression of FAP mRNA in OLK cells (2.63 ± 0.62) was higher than in NM cells (0.87 ± 0.14), but lower than in OSCC cells (5.63 ± 1.06; P = .027 and .012, respectively). FAP expression was minimal in NM cells (0.78 ± 0.06), modest in OLK cells (1.04 ± 0.06), and significantly elevated in OSCC cells (1.61 ± 0.09) based on the results of WB (P < .001). CONCLUSIONS: Significant variations in FAP expression were observed in NM, OLK, and OSCC tissues and cells. These findings revealed that FAP may be a reliable biomarker for the early diagnosis and evaluation of OLK carcinogenesis.

Dual aldehyde cross-linked hyaluronic acid hydrogels loaded with PRP and NGF biofunctionalized PEEK interfaces to enhance osteogenesis and vascularization.

Polyetheretherketone (PEEK) material has become a potential bone replacement material due to its elastic modulus, which is close to that of human bone, and stable chemical properties. However, its biological inertness has hindered its clinical application. To improve the biological inertia of PEEK material, a hyaluronic acid (HA) hydrogel coating loaded with platelet-rich plasma (PRP) and nerve growth factor (NGF) was constructed on the surface of PEEK material in this study. After the hybrid hydrogel coating was constructed, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FT-IR), degradation tests, and enzyme-linked immunosorbent assays (ELISAs) were used to evaluate its characteristics and biological properties. The osteogenic and angiogenic potentials were also investigated in vitro and in vivo. Our results showed that the HA hydrogel loaded with RPP and NGF on the PEEK surface degraded slowly and could sustainably release various growth factors, including NGF. The results of in vitro tests showed that the hybrid hydrogel on the surface of PEEK effectively promoted osteogenesis and angiogenesis. The in vivo experiment also confirmed that the PEEK surface hydrogel could promote osseointegration of the implant and the integration of new bone and neovascularization. Our results suggest that the cross-linked hyaluronic acid hydrogel loaded with PRP and NGF can significantly improve the biological inertia of PEEK material, endowing PEEK material with good osteogenic and angiogenic ability.

Lack of T04C9.1, the Homologue of Mammalian APPL2, Leads to Premature Ageing and Shortens Lifespan in Caenorhabditis elegans.

Ageing has been identified as an independent risk factor for various diseases; however, the physiological basis and molecular changes related to ageing are still largely unknown. Here, we show that the level of APPL2, an adaptor protein, is significantly reduced in the major organs of aged mice. Knocking down APPL2 causes premature ageing of human umbilical vein endothelial cells (HUVECs). We find that a lack of T04C9.1, the homologue of mammalian APPL2, leads to premature ageing, slow movements, lipid deposition, decreased resistance to stresses, and shortened lifespan in Caenorhabditis elegans (C. elegans), which are associated with decreased autophagy. Activating autophagy by rapamycin or inhibition of let-363 suppresses the age-related alternations, impaired motility, and shortened lifespan of C. elegans, which are reversed by knocking down autophagy-related genes. Our work provides evidence that APPL2 and its C. elegans homologue T04C9.1 decrease with age and reveals that a lack of T04C9.1 bridges autophagy decline and ageing in C. elegans.

Microglial EPOR Contribute to Sevoflurane-induced Developmental Fine Motor Deficits Through Synaptic Pruning in Mice.

Clinical researches including the Mayo Anesthesia Safety in Kids (MASK) study have found that children undergoing multiple anesthesia may have a higher risk of fine motor control difficulties. However, the underlying mechanisms remain elusive. Here, we report that erythropoietin receptor (EPOR), a microglial receptor associated with phagocytic activity, was significantly downregulated in the medial prefrontal cortex of young mice after multiple sevoflurane anesthesia exposure. Importantly, we found that the inhibited erythropoietin (EPO)/EPOR signaling axis led to microglial polarization, excessive excitatory synaptic pruning, and abnormal fine motor control skills in mice with multiple anesthesia exposure, and those above-mentioned situations were fully reversed by supplementing EPO-derived peptide ARA290 by intraperitoneal injection. Together, the microglial EPOR was identified as a key mediator regulating early synaptic development in this study, which impacted sevoflurane-induced fine motor dysfunction. Moreover, ARA290 might serve as a new treatment against neurotoxicity induced by general anesthesia in clinical practice by targeting the EPO/EPOR signaling pathway.

Fer-1 Protects against Isoflurane-Induced Ferroptosis in Astrocytes and Cognitive Impairment in Neonatal Mice.

Early and prolonged exposure to anesthetic agents could cause neurodevelopmental disorders in children. Astrocytes, heavily outnumber neurons in the brain, are crucial regulators of synaptic formation and function during development. However, how general anesthetics act on astrocytes and the impact on cognition are still unclear. In this study, we investigated the role of ferroptosis and GPX4, a major hydroperoxide scavenger playing a pivotal role in suppressing the process of ferroptosis, and their underlying mechanism in isoflurane-induced cytotoxicity in astrocytes and cognitive impairment. Our results showed that early 6 h isoflurane anesthesia induced cognitive impairment in mice. Ferroptosis-relative genes and metabolic changes were involved in the pathological process of isoflurane-induced cytotoxicity in astrocytes. The level of GPX4 was decreased while the expression of 4-HNE and generation of ROS were elevated after isoflurane exposure. Selectively blocking ferroptosis with Fer-1 attenuated the abovementioned cytotoxicity in astrocytes, paralleling with the reverse of the changes in GPX4, ROS and 4-HNE secondary to isoflurane anesthesia. Fer-1 attenuated the cognitive impairment induced by prolonged isoflurane exposure. Thus, ferroptosis conduced towards isoflurane-induced cytotoxicity in astrocytes via suppressing GPX4 and promoting lipid peroxidation. Fer-1 was expected to be an underlying intervention for the neurotoxicity induced by isoflurane in the developing brain, and to alleviate cognitive impairment in neonates.

Integrated ribosome and proteome analyses reveal insights into sevoflurane-induced long-term social behavior and cognitive dysfunctions through ADNP inhibition in neonatal mice.

A growing number of studies have demonstrated that repeated exposure to sevoflurane during development results in persistent social abnormalities and cognitive impairment. Davunetide, an active fragment of the activity-dependent neuroprotective protein (ADNP), has been implicated in social and cognitive protection. However, the potential of davunetide to attenuate social deficits following sevoflurane exposure and the underlying developmental mechanisms remain poorly understood. In this study, ribosome and proteome profiles were analyzed to investigate the molecular basis of sevoflurane-induced social deficits in neonatal mice. The neuropathological basis was also explored using Golgi staining, morphological analysis, western blotting, electrophysiological analysis, and behavioral analysis. Results indicated that ADNP was significantly down-regulated following developmental exposure to sevoflurane. In adulthood, anterior cingulate cortex (ACC) neurons exposed to sevoflurane exhibited a decrease in dendrite number, total dendrite length, and spine density. Furthermore, the expression levels of Homer, PSD95, synaptophysin, and vglut2 were significantly reduced in the sevoflurane group. Patch-clamp recordings indicated reductions in both the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs). Notably, davunetide significantly ameliorated the synaptic defects, social behavior deficits, and cognitive impairments induced by sevoflurane. Mechanistic analysis revealed that loss of ADNP led to dysregulation of Ca 2+ activity via the Wnt/ß-catenin signaling, resulting in decreased expression of synaptic proteins. Suppression of Wnt signaling was restored in the davunetide-treated group. Thus, ADNP was identified as a promising therapeutic target for the prevention and treatment of neurodevelopmental toxicity caused by general anesthetics. This study provides important insights into the mechanisms underlying social and cognitive disturbances caused by sevoflurane exposure in neonatal mice and elucidates the regulatory pathways involved.

Characterization of ultrasound-assisted covalent binding interaction between ß-lactoglobulin and dicaffeoylquinic acid: Great potential for the curcumin delivery.

The low bioavailability and poor gastrointestinal instability of curcumin hampers its application in pharmaceutical and food industries. Thus, it is essential to explore efficient carrier (e.g. a combination of polyphenols and proteins) for food systems. In this study, covalent ß-lactoglobulin (LG)-dicaffeoylquinic acids (DCQAs) complexes were prepared by combining ultrasound and free radical induction methods. Covalent interactions between LG and DCQAs were confirmed by analyzing reactive groups. Variations in secondary or tertiary structure and potential binding sites of covalent complexes were explored using Fourier transform infrared spectroscopy and circular dichroism. Results showed that the ß-sheet content decreased and the unordered content increased significantly (P < 0.05). The embedding rate of curcumin in prepared LG-DCQAs complexes using ultrasound could reach 49 % - 62 %, proving that complexes could embed curcumin effectively. This study highlights the benefit of ultrasound application in fabrication of protein-polyphenol complexes for delivering curcumin.

Strategies of immobilizing BMP-2 with 3D-printed scaffolds to improve osteogenesis.

The management and definitive treatment of critical-size bone defects in severe trauma, tumor resection and congenital malformation are troublesome for orthopedic surgeons and patients worldwide without recognized good treatment strategies. Researchers and clinicians are working to develop new strategies to treat these problems. This review aims to summarize the techniques used by additive manufacturing scaffolds loaded with BMP-2 to promote osteogenesis and to analyze the current status and trends in relevant clinical translation. Optimize composite scaffold design to enhance bone regeneration through printing technology, material selection, structure design and loading methods of BMP-2 to advance the clinical therapeutic bone repair field.

Some people have considerable bone gaps because of accidents, cancer or congenital disabilities. These gaps are difficult to heal and can cause many problems. Doctors and scientists are trying to find new ways to help these people. One way is to make artificial pieces of bone that can fit into the gaps and help the bone grow back. These are made using special machines that can print different shapes and materials. They also contain a protein called BMP-2, which allows the bones to grow faster. This article examines how these parts are made and how they can be used in patients. It also suggests how they might be improved in the future.

Newly discovered circRNAs encoding proteins: recent progress.

Circular RNA (circRNA) is a special class of noncoding RNA molecules and the latest research hotspot in the field of RNA. CircRNA molecules have a closed loop structure, which is not affected by RNA exonuclease and has the characteristics of more stable expression. Previous studies have shown that circRNA molecules are rich in microRNA (miRNA) binding sites and act as miRNA sponges in cells. By interacting with miRNAs associated with tumors and other diseases, circRNAs play an important regulatory role. However, circRNAs have recently been found to have small open reading frames that enable them to encode peptides/proteins. These proteins have been reported to play an important role in the mechanism of regulation of a variety of diseases and have great potential in the diagnosis and treatment of diseases. In this review, we summarize the mechanism of action of the newly discovered circRNA-coding proteins since 2022 and briefly describe their research process. In addition, we also discuss the prediction model of the functional sites and encoded proteins of circRNAs, which provides a potential idea for future research on circRNAs.