Dental Age Estimation in Northern Chinese Han Children and Adolescents Using Demirjian's Method Combined with Machine Learning Algorithms.

OBJECTIVES: To investigate the application value of combining the Demirjian's method with machine learning algorithms for dental age estimation in northern Chinese Han children and adolescents. METHODS: Oral panoramic images of 10 256 Han individuals aged 5 to 24 years in northern China were collected. The development of eight permanent teeth in the left mandibular was classified into different stages using the Demirjian's method. Various machine learning algorithms, including support vector regression (SVR), gradient boosting regression (GBR), linear regression (LR), random forest regression (RFR), and decision tree regression (DTR) were employed. Age estimation models were constructed based on total, female, and male samples respectively using these algorithms. The fitting performance of different machine learning algorithms in these three groups was evaluated. RESULTS: SVR demonstrated superior estimation efficiency among all machine learning models in both total and female samples, while GBR showed the best performance in male samples. The mean absolute error (MAE) of the optimal age estimation model was 1.246 3, 1.281 8 and 1.153 8 years in the total, female and male samples, respectively. The optimal age estimation model exhibited varying levels of accuracy across different age ranges, which provided relatively accurate age estimations in individuals under 18 years old. CONCLUSIONS: The machine learning model developed in this study exhibits good age estimation efficiency in northern Chinese Han children and adolescents. However, its performance is not ideal when applied to adult population. To improve the accuracy in age estimation, the other variables can be considered.

Insights into the removal of antibiotics from livestock and aquaculture wastewater by algae-bacteria symbiosis systems.

With the burgeoning growth of the livestock and aquaculture industries, antibiotic residues in treated wastewater have become a serious ecological threat. Traditional biological wastewater treatment technologies-while effective for removing conventional pollutants, such as organic carbon, ammonia and phosphate-struggle to eliminate emerging contaminants, notably antibiotics. Recently, the use of microalgae has emerged as a sustainable and promising approach for the removal of antibiotics due to their non-target status, rapid growth and carbon recovery capabilities. This review aims to analyse the current state of antibiotic removal from wastewater using algae-bacteria symbiosis systems and provide valuable recommendations for the development of livestock/aquaculture wastewater treatment technologies. It (1) summarises the biological removal mechanisms of typical antibiotics, including bioadsorption, bioaccumulation, biodegradation and co-metabolism; (2) discusses the roles of intracellular regulation, involving extracellular polymeric substances, pigments, antioxidant enzyme systems, signalling molecules and metabolic pathways; (3) analyses the role of treatment facilities in facilitating algae-bacteria symbiosis, such as sequencing batch reactors, stabilisation ponds, membrane bioreactors and bioelectrochemical systems; and (4) provides insights into bottlenecks and potential solutions. This review offers valuable information on the mechanisms and strategies involved in the removal of antibiotics from livestock/aquaculture wastewater through the symbiosis of microalgae and bacteria.

Isorhapontigenin inhibition of basal muscle-invasive bladder cancer attributed to its downregulation of SNHG1 and DNMT3b.

BACKGROUND: Bladder cancer (BC) is among the most prevalent malignant urothelial tumors globally, yet the prognosis for patients with muscle-invasive bladder cancer (MIBC) remains dismal, with a very poor 5-year survival rate. Consequently, identifying more effective and less toxic chemotherapeutic alternatives is critical for enhancing clinical outcomes for BC patients. Isorhapontigenin (ISO), a novel stilbene isolated from a Gnetum found in certain provinces of China, has shown potential as an anticancer agent due to its diverse anticancer activities. Despite its promising profile, the specific anticancer effects of ISO on BC and the underlying mechanisms are still largely unexplored. METHODS: The anchorage-independent growth, migration and invasion of BC cells were assessed by soft agar and transwell invasion assays, respectively. The RNA levels of SOX2, miR-129 and SNHG1 were quantified by qRT-PCR, while the protein expression levels were validated through Western blotting. Furthermore, methylation-specific PCR was employed to assess the methylation status of the miR-129 promoter. Functional assays utilized siRNA knockdown, plasmid-mediated overexpression, and chemical inhibition approaches. RESULTS: Our study demonstrated that ISO treatment significantly reduced SNHG1 expression in a dose- and time-dependent manner in BC cells, leading to the inhibition of anchorage-independent growth and invasion in human basal MIBC cells. This effect was accompanied by the downregulation of MMP-2 and MMP-9 and the upregulation of the tumor suppressor PTEN. Further mechanistic investigations revealed that SOX2, a key upstream regulator of SNHG1, played a crucial role in mediating the ISO-induced transcriptional suppression of SNHG1. Additionally, we found that ISO treatment led to a decrease in DNMT3b protein levels, which in turn mediated the hypomethylation of the miR-129 promoter and the subsequent suppression of SOX2 mRNA 3'-UTR activity, highlighting a novel pathway through which ISO exerts its anticancer effects. CONCLUSIONS: Collectively, our study highlights the critical role of SNHG1 downregulation as well as its upstream DNMT3b/miR-129/SOX2 axis in mediating ISO anticancer activity. These findings not only elucidate the mechanism of action of ISO but also suggest novel targets for BC therapy.

Organic Passivation-Enhanced Ferroelectricity in Perovskite Oxide Films.

Perovskite oxides and organic-inorganic halide perovskite materials, with numerous fascinating features, have been subjected to extensive studies. Most of the properties of perovskite materials are dependence on their ferroelectricity that denoted by remanent polarization (Pr). Thus, the increase of Pr in perovskite films is mainly an effort in material physics. At present, commonplace improvement schemes, i.e., controlling material crystallinity, and post-annealing by using a high-temperature process, are normally used. However, a simpler and temporal strategy for Pr improvement is always unavailable to perovskite material researchers. In this study, an organic coating layer, low-temperature, and vacuum-free strategy is proposed to improve the Pr, directly increasing the Pr from 36 to 56 µC cm-2. Further study finds that the increased Pr originates from the suppression of the oxygen defects and Ti defects. This organic coating layer strategy for passivating the defects may open a new way for the preparation of higher-performance and cost-effective perovskite products, further improving its prospective for application in the electron devices field.

Estrogen influences the transzonal projection assembly of cumulus-oocyte complexes through G protein-coupled estrogen receptor during goat follicle development.

Estrogen is an important hormone that plays a role in regulating follicle development and oocyte maturation. Transzonal projections (TZPs) act as communication bridges between follicle somatic cells and oocytes, and their dynamic changes are critical for oocyte development and maturation. However, the roles and mechanisms of estrogen in regulating TZPs during follicular development are not yet understood. We found that the proportion of oocytes spontaneously resuming meiosis increases as the follicle grows, which is accompanied by rising estrogen levels in follicles and decreasing TZPs in cumulus-oocyte complex. To further explore the effect of elevated estrogen levels on TZP assembly, additional estrogen was added to the culture system. The increased estrogen level significantly decreased the mRNA and protein expression levels of TZP assembly-related genes. Subsequent research revealed that TZP regulation by estrogen was mediated by the membrane receptor GPER and downstream ERK1/2 signaling pathway. In summary, our study suggests that estrogen may regulate goat oocyte meiosis arrest by decreasing TZP numbers via estrogen-mediated GPER activation during follicle development.

Communication behavior recognition using CNN-based signal analysis.

This article explores the technology of recognizing non-cooperative communication behavior, with a specific emphasis on analyzing communication station signals. Conventional techniques for analyzing signal data frames to determine their identity, while precise, do not have the ability to operate in real-time. In order to tackle this issue, we developed a pragmatic architecture for recognizing communication behavior and a system based on polling. The method utilizes a one-dimensional convolutional neural network (CNN) to segment data, hence improving its ability to recognize various communication activities. The study assesses the reliability of CNN in several real-world scenarios, examining its accuracy in the presence of noise interference, varying lengths of interception signals, interferences at different frequency points, and dynamic changes in outpost locations. The experimental results confirm the efficacy and dependability of the convolutional neural network in recognizing communication behavior in various contexts.

A Personalized Music Intervention in Nursing Home Residents Living With Dementia: Findings From a Randomized Study.

Utilizing a randomized control design, this mixed method study aimed to assess the impact of a personalized music intervention on mood, agitation level, and psychotropic drug use in individuals with moderate to advanced dementia residing in long-term care facilities. The sample comprised of 261 participants, with 148 in the intervention group and 113 in the control group. Data were collected from three sources: quantitative data from the Minimum Data Set and the Cohen-Mansfield Agitation Inventory, observational data of music-listening sessions, and an administrator survey regarding the lead staff person's perceptions of the intervention. Findings, based on Mixed Effect Models and content analyses, revealed positive impacts of the personalized music intervention on residents living with dementia. This low-cost, easily implementable intervention, requiring no special licensure for administration, can significantly enhance the quality of life for nursing facility residents.

Covalent targeted radioligands potentiate radionuclide therapy.

Targeted radionuclide therapy, in which radiopharmaceuticals deliver potent radionuclides to tumours for localized irradiation, has addressed unmet clinical needs and improved outcomes for patients with cancer1-4. A therapeutic radiopharmaceutical must achieve both sustainable tumour targeting and fast clearance from healthy tissue, which remains a major challenge5,6. A targeted ligation strategy that selectively fixes the radiopharmaceutical to the target protein in the tumour would be an ideal solution. Here we installed a sulfur (VI) fluoride exchange (SuFEx) chemistry-based linker on radiopharmaceuticals to prevent excessively fast tumour clearance. When the engineered radiopharmaceutical binds to the tumour-specific protein, the system undergoes a binding-to-ligation transition and readily conjugates to the tyrosine residues through the 'click' SuFEx reaction. The application of this strategy to a fibroblast activation protein (FAP) inhibitor (FAPI) triggered more than 80% covalent binding to the protein and almost no dissociation for six days. In mice, SuFEx-engineered FAPI showed 257% greater tumour uptake than did the original FAPI, and increased tumour retention by 13-fold. The uptake in healthy tissues was rapidly cleared. In a pilot imaging study, this strategy identified more tumour lesions in patients with cancer than did other methods. SuFEx-engineered FAPI also successfully achieved targeted ß- and α-radionuclide therapy, causing nearly complete tumour regression in mice. Another SuFEx-engineered radioligand that targets prostate-specific membrane antigen (PSMA) also showed enhanced therapeutic efficacy. Considering the broad scope of proteins that can potentially be ligated to SuFEx warheads, it might be possible to adapt this strategy to other cancer targets.

Different machine learning methods based on maxillary sinus in sex estimation for northwestern Chinese Han population.

BACKGROUND & OBJECTIVE: Sex estimation is a critical aspect of forensic expertise. Some special anatomical structures, such as the maxillary sinus, can still maintain integrity in harsh environmental conditions and may be served as a basis for sex estimation. Due to the complex nature of sex estimation, several studies have been conducted using different machine learning algorithms to improve the accuracy of sex prediction from anatomical measurements. MATERIAL & METHODS: In this study, linear data of the maxillary sinus in the population of northwest China by using Cone-Beam Computed Tomography (CBCT) were collected and utilized to develop logistic, K-Nearest Neighbor (KNN), Support Vector Machine (SVM) and random forest (RF) models for sex estimation with R 4.3.1. CBCT images from 477 samples of Han population (75 males and 81 females, aged 5-17 years; 162 males and 159 females, aged 18-72) were used to establish and verify the model. Length (MSL), width (MSW), height (MSH) of both the left and right maxillary sinuses and distance of lateral wall between two maxillary sinuses (distance) were measured. 80% of the data were randomly picked as the training set and others were testing set. Besides, these samples were grouped by age bracket and fitted models as an attempt. RESULTS: Overall, the accuracy of the sex estimation for individuals over 18 years old on the testing set was 77.78%, with a slightly higher accuracy rate for males at 78.12% compared to females at 77.42%. However, accuracy of sex estimation for individuals under 18 was challenging. In comparison to logistic, KNN and SVM, RF exhibited higher accuracy rates. Moreover, incorporating age as a variable improved the accuracy of sex estimation, particularly in the 18-27 age group, where the accuracy rate increased to 88.46%. Meanwhile, all variables showed a linear correlation with age. CONCLUSION: The linear measurements of the maxillary sinus could be a valuable tool for sex estimation in individuals aged 18 and over. A robust RF model has been developed for sex estimation within the Han population residing in the northwestern region of China. The accuracy of sex estimation could be higher when age is used as a predictive variable.

Alemtuzumab induction is associated with decreased hospitalization rates in pediatric kidney transplant: A UNOS data review for safety and outcomes with common induction regimens.

BACKGROUND: We hypothesized that alemtuzumab use is safe in pediatric kidney transplant recipients (KTRs) with equivalent long-term outcomes compared to other induction agents. METHODS: Using pediatric kidney transplant recipient data in the UNOS database between January 1, 2000, and June 30, 2022, multivariate logistic regression, multivariable Cox regression, and survival analyses were utilized to estimate the likelihoods of 1st-year and all-time hospitalizations, acute rejection, CMV infection, delayed graft function (DGF), graft loss, and patient mortality among recipients of three common induction regimens (ATG, alemtuzumab, and basiliximab). RESULTS: There were no differences in acute rejection or graft failure among induction or maintenance regimens. Basiliximab was associated with lower odds of DGF in deceased donor recipients (OR 0.77 [0.60-0.99], p = .04). Mortality was increased in patients treated with steroid-containing maintenance (HR 1.3 [1.005-1.7] p = .045). Alemtuzumab induction correlated with less risk of CMV infection than ATG (OR 0.76 [0.59-0.99], p = .039). Steroid-containing maintenance conferred lower rate of PTLD compared to steroid-free maintenance (HR 0.59 [0.4-0.8] p = .001). Alemtuzumab was associated with less risk of hospitalization within 1 year (OR 0.79 [0.67-0.95] p = .012) and 5 years (HR 0.54 [0.46-0.65] p < .001) of transplantation. Steroid maintenance also decreased 5 years hospitalization risk (HR 0.78 [0.69-0.89] p < .001). CONCLUSIONS: Pediatric KTRs may be safely treated with alemtuzumab induction without increased risk of acute rejection, DGF, graft loss, or patient mortality. The decreased risk of CMV infections and lower hospitalization rates compared to other agents make alemtuzumab an attractive choice for induction in pediatric KTRs, especially in those who cannot tolerate ATG.

Effects of interleukin-10 treated macrophages on bone marrow mesenchymal stem cells via signal transducer and activator of transcription 3 pathway.

BACKGROUND: Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved. Regulating the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair process. AIM: To assess the influence of interleukin-10 (IL-10) on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) following their interaction with macrophages in an inflammatory environment. METHODS: IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory environment. In this study, we investigated its impact on the proliferation, migration, and osteogenesis of BMSCs. The expression levels of signal transducer and activator of transcription 3 (STAT3) and its activated form, phosphorylated-STAT3, were examined in IL-10-stimulated macrophages. Subsequently, a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 signaling. RESULTS: IL-10-stimulated macrophages underwent polarization to the M2 type through substitution, and these M2 macrophages actively facilitated the osteogenic differentiation of BMSCs. Mechanistically, STAT3 signaling plays a crucial role in the process by which IL-10 influences macrophages. Specifically, IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response, as evidenced by its diminished impact on the osteogenic differentiation of BMSCs. CONCLUSION: Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of BMSCs. The IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs' osteogenic differentiation.

FMNL2 regulates actin for endoplasmic reticulum and mitochondria distribution in oocyte meiosis.

During mammalian oocyte meiosis, spindle migration and asymmetric cytokinesis are unique steps for the successful polar body extrusion. The asymmetry defects of oocytes will lead to the failure of fertilization and embryo implantation. In present study, we reported that an actin nucleating factor Formin-like 2 (FMNL2) played critical roles in the regulation of spindle migration and organelle distribution in mouse and porcine oocytes. Our results showed that FMNL2 mainly localized at the oocyte cortex and periphery of spindle. Depletion of FMNL2 led to the failure of polar body extrusion and large polar bodies in oocytes. Live-cell imaging revealed that the spindle failed to migrate to the oocyte cortex, which caused polar body formation defects, and this might be due to the decreased polymerization of cytoplasmic actin by FMNL2 depletion in the oocytes of both mice and pigs. Furthermore, mass spectrometry analysis indicated that FMNL2 was associated with mitochondria and endoplasmic reticulum (ER)-related proteins, and FMNL2 depletion disrupted the function and distribution of mitochondria and ER, showing with decreased mitochondrial membrane potential and the occurrence of ER stress. Microinjecting Fmnl2-EGFP mRNA into FMNL2-depleted oocytes significantly rescued these defects. Thus, our results indicate that FMNL2 is essential for the actin assembly, which further involves into meiotic spindle migration and ER/mitochondria functions in mammalian oocytes.

Facilitating the dry reforming of methane with interfacial synergistic catalysis in an Ir@CeO2-x catalyst.

The dry reforming of methane provides an attractive route to convert greenhouse gases (CH4 and CO2) into valuable syngas, so as to resolve the carbon cycle and environmental issues. However, the development of high-performance catalysts remains a huge challenge. Herein, we report a 0.6% Ir/CeO2-x catalyst with a metal-support interface structure which exhibits high CH4 (~72%) and CO2 (~82%) conversion and a CH4 reaction rate of ~973 µmolCH4 gcat-1 s-1 which is stable over 100 h at 700 °C. The performance of the catalyst is close to the state-of-the-art in this area of research. A combination of in situ spectroscopic characterization and theoretical calculations highlight the importance of the interfacial structure as an intrinsic active center to facilitate the CH4 dissociation (the rate-determining step) and the CH2* oxidation to CH2O* without coke formation, which accounts for the long-term stability. The catalyst in this work has a potential application prospect in the field of high-value utilization of carbon resources.

Dietary fiber may benefit chondrocyte activity maintenance.

The understanding of the link between the gut-bone axis is growing yearly, but the mechanisms involved are not yet clear. Our study analyzed the role of Sestrin2 (SESN2)pathway in the gut-bone axis. We established an osteoarthritis (OA) model in Sprague-Dawley (SD) rats using the anterior cruciate ligament transection (ACLT) procedure, followed by a dietary intervention with varying levels of dietary fiber content for 8 weeks. By 16S rRNA sequencing of the gut microbiota, we found that high dietary fiber (HDF) intake could significantly increase the Bacillota-dominant gut microbiota. Meanwhile, enzyme linked immunosorbent assay (ELISA) and histological analysis showed that intervention with HDF could reduce the degree of bone and joint lesions and inflammation. We hypothesize that HDF increased the dominant flora of Bacillota, up-regulated the expression of SESN2 in knee joint, and reduced gut permeability, thereby reducing systemic inflammatory response and the degree of bone and joint lesions. Therefore, the present study confirms that changes in gut microbiota induced by increased dietary fiber intake delayed the onset of OA by promoting up-regulation of SESN2 expression at the knee joint to maintain chondrocyte activity and reduce synovial inflammation.

Mitochondrial genome data provide insights into the phylogenetic relationships within Triplophysadalaica (Kessler, 1876) (Cypriniformes, Nemacheilidae).

Due to the detrimental effect of formaldehyde on DNA, ethanol has replaced formalin as the primary preservative for animal specimens. However, short-term formalin fixation of specimens might be applied during field collection. In an increasing number of studies, DNA extraction and sequencing have been successfully conducted from formalin-fixed specimens. Here the DNA from five specimens of Triplophysadalaica (Kessler, 1876) were extracted and performed high-throughput sequencing. Four of the specimens underwent short-term fixation with formalin and were subsequently transferred to ethanol. One was continuously stored in ethanol. No significant difference of DNA quality and amount were observed among these samples. Followed by assembly and annotation, five mitochondrial genomes ranging in length from 16,569 to 16,572 bp were obtained. Additionally, previously published data of other individuals or species were included to perform phylogenetic analyses. In the reconstructed trees, all eight individuals of T.dalaica form a monophyletic group within the Triplophysa branch. The group is divided into three clades: (1) samples from the Yellow River, (2) those from the Yangtze River, and (3) those from the Haihe River, and the Lake Dali Nur. This study sheds initial light on the phylogeographic relationships among different populations of T.dalaica, and will support the research about its evolutionary history in the future.

Intermittent hypoxic pretreatment exacerbates house dust mite-induced asthma airway inflammation.

BACKGROUND: Asthma is widely recognized as an inflammatory disorder. In the context of this inflammatory microenvironment, the involvement of hypoxia and its impact on related pathways have drawn considerable attention. However, the exact role of hypoxia, a prevalent environmental factor, in the development and progression of asthma remains poorly understood. METHODS: Mice were treated with house dust mite (HDM) extracts for 23 days to induce asthma. Mice were divided into room air (RA) group and intermittent hypoxic (IH) group by exposing to different conditions and IH preconditioning (IHP) were underwent to the above groups before the hypoxic regimen. Airway inflammation in mice was evaluated by airway hyperresponsiveness, excessive mucus secretion, and recruitment of inflammatory cells. Immunohistochemistry was employed to quantify the expression levels of NF-κB. Subsequently, the dose of allergen was modified to investigate whether the impact of hypoxia on asthma is affected by different doses of allergens. RESULT: Compared to the RA and IH groups, HDM-treated mice in the IHP group exhibited aggravated inflammatory cell infiltration and airway hyperresponsiveness (p＜.05). Moreover, there was an increased release of inflammatory mediators and higher expression levels of NF-κB (p＜.05). Importantly, the impact ia on asthma was found to be influenced by high dose of allergen (p＜.05). CONCLUSION: IHP treatment potentially exacerbates HDM-induced airway inflammation in asthma, with the involvement of NF-κB, particularly under high-dose allergen stimulation.

Long-term conservation tillage increase cotton rhizosphere sequestration of soil organic carbon by changing specific microbial CO2 fixation pathways in coastal saline soil.

Coastal saline soil is an important reserve resource for arable land globally. Data from 10 years of continuous stubble return and subsoiling experiments have revealed that these two conservation tillage measures significantly improve cotton rhizosphere soil organic carbon sequestration in coastal saline soil. However, the contribution of microbial fixation of atmospheric carbon dioxide (CO2) has remained unclear. Here, metagenomics and metabolomics analyses were used to deeply explore the microbial CO2 fixation process in rhizosphere soil of coastal saline cotton fields under long-term stubble return and subsoiling. Metagenomics analysis showed that stubble return and subsoiling mainly optimized CO2 fixing microorganism (CFM) communities by increasing the abundance of Acidobacteria, Gemmatimonadetes, and Chloroflexi, and improving composition diversity. Conjoint metagenomics and metabolomics analyses investigated the effects of stubble return and subsoiling on the reverse tricarboxylic acid (rTCA) cycle. The conversion of citrate to oxaloacetate was inhibited in the citrate cleavage reaction of the rTCA cycle. More citrate was converted to acetyl-CoA, which enhanced the subsequent CO2 fixation process of acetyl-CoA conversion to pyruvate. In the rTCA cycle reductive carboxylation reaction from 2-oxoglutarate to isocitrate, synthesis of the oxalosuccinate intermediate product was inhibited, with strengthened CO2 fixation involving the direct conversion of 2-oxoglutarate to isocitrate. The collective results demonstrate that stubble return and subsoiling optimizes rhizosphere CFM communities by increasing microbial diversity, in turn increasing CO2 fixation by enhancing the utilization of rTCA and 3-hydroxypropionate/4-hydroxybutyrate cycles by CFMs. These events increase the microbial CO2 fixation in the cotton rhizosphere, thereby promoting the accumulation of microbial biomass, and ultimately improving rhizosphere soil organic carbon. This study clarifies the impact of conservation tillage measures on microbial CO2 fixation in cotton rhizosphere of coastal saline soil, and provides fundamental data for the improvement of carbon sequestration in saline soil in agricultural ecosystems.

FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection.

The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in ß cells. This upregulation increases both insulin secretion and susceptibility of ß cells to SARS-CoV-2 infection. Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation, subsequently reducing viral infection and replication in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms. Finally, animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels, resulting in a reduction of insulin concentrations in situ. Taken together, our research offers a potential regulatory strategy for ACE2 by controlling FGF7, thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.

Exploring the Prospects of Transcranial Electrical Stimulation (tES) as a Therapeutic Intervention for Post-Stroke Motor Recovery: A Narrative Review.

INTRODUCTION: Stroke survivors often have motor impairments and related functional deficits. Transcranial Electrical Stimulation (tES) is a rapidly evolving field that offers a wide range of capabilities for modulating brain function, and it is safe and inexpensive. It has the potential for widespread use for post-stroke motor recovery. Transcranial Direct Current Stimulation (tDCS), Transcranial Alternating Current Stimulation (tACS), and Transcranial Random Noise Stimulation (tRNS) are three recognized tES techniques that have gained substantial attention in recent years but have different mechanisms of action. tDCS has been widely used in stroke motor rehabilitation, while applications of tACS and tRNS are very limited. The tDCS protocols could vary significantly, and outcomes are heterogeneous. PURPOSE: the current review attempted to explore the mechanisms underlying commonly employed tES techniques and evaluate their prospective advantages and challenges for their applications in motor recovery after stroke. CONCLUSION: tDCS could depolarize and hyperpolarize the potentials of cortical motor neurons, while tACS and tRNS could target specific brain rhythms and entrain neural networks. Despite the extensive use of tDCS, the complexity of neural networks calls for more sophisticated modifications like tACS and tRNS.

SLC7A11 inhibits ferroptosis and downregulates PD-L1 levels in lung adenocarcinoma.

Introduction: Lung adenocarcinoma (LUAD) is a prevalent form of lung cancer originating from lung glandular cells with low survival rates despite recent therapeutic advances due to its diverse and complex nature. Recent evidence suggests a link between ferroptosis and the effectiveness of anti-PD-L1 therapy, with potential synergistic effects. Methods: Our study comprehensively analyzed the expression patterns of ferroptosis regulators in LUAD and their association with prognosis and PD-L1 expression. Furthermore, we identified two distinct subtypes of LUAD through consensus clustering of ferroptosis regulators, revealing significant tumor heterogeneity, divergent PD-L1 expression, and varying prognoses between the subtypes. Results: Among the selected ferroptosis regulators, SLC7A11 emerged as an independent prognostic marker for LUAD patients and exhibited a negative correlation with PD-L1 expression. Subsequent investigations revealed high expression of SLC7A11 in the LUAD population. In vitro experiments demonstrated that overexpression of SLC7A11 led to reduced PD-L1 expression and inhibited ferroptosis in A549 cells, underscoring the significant role of SLC7A11 in LUAD. Additionally, pan-cancer analyses indicated an association between SLC7A11 and the expression of immune checkpoint genes across multiple cancer types with poor prognoses. Discussion: From a clinical standpoint, these findings offer a foundation for identifying and optimizing potential combination strategies to enhance the therapeutic effectiveness of immune checkpoint inhibitors and improve the prognosis of patients with LUAD.