Fetal Biometric Parameter Reference Charts of a Central Anatolian Turkish Population.

PURPOSE: The assessment of fetal biometry using ultrasound provides accurate pregnancy dating and also screening of fetal growth. Fetal biometry, which is common practice in the second and third trimesters of pregnancy, is fetal morphometry, which involves taking measurements of the different anatomical body parts. These fetal dimensions vary on ethnicity. The aim of this study is to demonstrate fetal biometric parameters measurement results of the Central Anatolia Turkish population with detailed percentile tables and graphs to screen fetal growth more accurately. METHODS: This cross-sectional study was performed on a total of 1132 fetuses (47% girl, and 53% boy) between 15 and 40 weeks of gestation. Biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) measurements are performed in a standardized manner every gestational week. BPD and HC were measured at the level of the thalami on the horizontal plane of the fetal head. HC was measured using the ellipse method. AC measurement was taken at the circular cross-section of the upper fetal abdomen. FL was measured along with the ossified diaphysis of the femur. All measurements were taken in millimeters. RESULTS: Pregnant women's mean age was 27.58 (17-43), and the mean body mass index was 27.68 (15.06-50.78) as demographic data. 38.13% of women had their first, 29.74% had their second, and 32.13% had three or more gestations within our study. Percentile data of fetuses for each parameter (BPD, HC, AC, and FL) and for each week were shown as tables and percentile graphics. Fetal 50th percentile measurements were compared between our study and other studies from different countries. The Kruskal-Wallis test results showed that BPD (p = 0.827), HC (p = 0.808), AC (p = 0.846), and FL (p = 0.725) values have a statistically similar mean in all studies. Hierarchical cluster analysis results showed that our results for BPD, HC, AC, and FL percentile curves have been found closer to Italian population results. However, our results were statistically different from Asian, Nigerian, non-Hispanic American, and Brazilian populations for each of the different parameters. CONCLUSION: The specialization of fetal biometric charts for a particular population can ensure a more accurate assessment of fetal growth rate. We showed fetal biometric percentile tables and graphics of the Central Anatolian Turkish population in this study. These results may provide a valuable contribution to obstetrical practice. Further studies can be conducted in different regions of Turkiye, thus comparisons could be possible over the country.

Comparative Assessment of Various Cephalometric Parameters Used for Determining Vertical Skeletal Dysplasia.

INTRODUCTION: The aim of the study is to assess and correlate the different cephalometric parameters used to determine the vertical jaw relationship. METHODS: Cephalometric radiographs from 148 patients were assessed and comparison was made using all eight parameters. Statistical analysis was performed using mean, standard deviation and coefficient of variance. A correlation was found between different variables using the Pearson's correlation coefficient. RESULTS: In the entire sample, the basal plane angle displayed the most variable distribution, while the R angle displayed the most homogeneous distribution. There was a significant correlation found between the Jarabak ratio, Steiner's mandibular plane angle (SN-GoGn), Frankfort mandibular plane angle (FMA), R angle, and DR angle. There was a moderate to weak correlation between the Y-axis, basal plane angle, and facial height ratio with other skeletal analyses. CONCLUSION: Among angular variables DR angle, R angle, SN-GoGn and FMA can be used and among linear variables Jarabak ratio could be used reliably to assess the growth pattern. It suggested that in order to obtain an accurate evaluation of the vertical jaw relationship, a variety of measurements should be combined.

Delayed Postoperative Intracerebral Hemorrhage Associated With Oral Multikinase Inhibitor Therapy for Cancer: A Case Report.

Regorafenib is a multikinase inhibitor with anti-vascular endothelial growth factor receptor (VEGF) activity used as an antiangiogenic agent for metastatic colorectal cancer treatment and has been studied as a potential therapeutic agent for several other cancer treatments. Adverse reactions commonly reported with the use of regorafenib and similar oral multikinase inhibitors include hemorrhage, gastrointestinal fistulas, hypertension, and incomplete wound healing. We report a case of a 59-year-old man with metastatic colorectal adenocarcinoma post-colostomy on regorafenib treatment presenting to the emergency department with altered mental status. MRI showed a left frontoparietal mass, which was resected with a left frontal craniotomy. Postoperative MRI showed a resection cavity without significant hemorrhage. He had been prescribed regorafenib preceding his hospitalization, which was continued after admission before surgery and on postoperative day 1. Thirty-two hours after surgery, the patient exhibited sudden right-sided facial droop and right arm weakness. Imaging revealed an acute intraparenchymal hemorrhage within and adjacent to the tumor resection bed, which was managed conservatively. The patient was subsequently discharged to an inpatient rehabilitation facility. The unusual timing of the hemorrhage suggests that the hemorrhage was due to adverse effects of regorafenib. Patients undergoing neurosurgery should have regorafenib discontinued in preparation for surgery. Similar management should be considered for other anti-VEGF medications to avoid serious complications.

A Massive Growth in the Palate: A Case Report.

This case report describes a 67-year-old woman who developed an extensive, slow-growing lesion occupying the whole of the palate in 10 years. Considering clinical and radiographic features, calcifying neoplasms were considered. Correlating microscopic features with clinical features, the lesion was diagnosed as peripheral ossifying fibroma, which seldom presents as an extensive lesion on the palate amongst the elderly age group. This case report will highlight clinicians and pathologists about a rare presentation of a commonly encountered lesion with a comprehensive view of the differential diagnosis of other comparable lesions.

Partially substituting alfalfa hay with hemp forage in the diet of goats improved feed efficiency, ruminal fermentation pattern and microbial profiles.

The use of hemp as a forage source in livestock diets has been less studied because bioactive residues in animal tissues may pose a risk to consumers. This study investigated the effects of partial substitution of alfalfa hay (AH) with hemp forage (HF) in growing goat diets on growth performance, carcass traits, ruminal fermentation characteristics, rumen microbial communities, blood biochemistry, and antioxidant indices. Forty Xiangdong black goats with body weight (BW) 7.82 ± 0.57 kg (mean ± SD) were grouped by BW and randomly assigned into one of the four treatment diets (n = 10/treatment) in a completely randomized design. The goats were fed ad libitum total mixed rations containing 60% forage and 40% concentrate (DM basis). The diets included control (CON; 60% AH and 40% concentrate), 55% AH and 5% HF (HF5), 50% AH and 10% HF (HF10), and 40% AH and 20% HF (HF20). Increasing the substitution of HF for AH linearly decreased (P < 0.01) DM intake and improved feed conversion efficiency. However, final BW, average daily gain, carcass traits, meat quality, and most blood biochemistry indices did not differ among treatments. The ruminal NH3-N concentration and blood urine nitrogen linearly increased (P < 0.01) with increasing substitution rate of HF, whereas the total volatile fatty acids concentration quadratically changed (P < 0.01). Substitution of AH with HF had no effect on the diversity and richness of ruminal microbes, though it linearly decreased (P = 0.040) Prevotella_1 and linearly increased (P = 0.017) Rikenellaceae_RC9_gut_group. The cannabinoids and/or their metabolites were detected in both ruminal filtrates (8) and plasma (4), however, no detectable cannabinoid-related residues were observed in meat. These results indicate that the HF could be used to partially substitute AH in goat diets, whereas the effects vary between substitution rates of HF for AH. Although no cannabinoid-related residues were detected in meat, the presence of cannabinoids residues in blood warrants further study of HF feeding to confirm the cannabinoids residues are not present in the animal products.

Can diffusion tensor imaging unlock the secrets of the growth plate?

"How tall will I be?" Every paediatrician has been asked this during their career. The growth plate is the main site of longitudinal growth of the long bones. The chondrocytes in the growth plate have a columnar pattern detectable by diffusion tensor imaging (DTI). DTI shows the diffusion of water in a tissue and whether it is iso- or anisotropic. By detecting direction and magnitude of diffusion, DTI gives information about the microstructure of the tissue. DTI metrics include tract volume, length, and number, fractional anisotropy (FA), and mean diffusivity. DTI metrics, particularly tract volume, provide quantitative data regarding skeletal growth and, in conjunction with the fractional anisotropy, be used to determine whether a growth plate is normal. Tractography is a visual display of the diffusion, depicting its direction and amplitude. Tractography gives a more qualitative visualization of cellular orientation in a tissue and reflects the activity in the growth plate. These two components of DTI can be used to assess the growth plate without ionizing radiation or pain. Further refinements in DTI will improve prediction of post-imaging growth and growth plate closure, and assessment of the positive and negative effect of treatments like cis-retinoic acid and growth hormone administration.

CRISPR/Cpf1-FOKI-induced gene editing in Gluconobacter oxydans.

Gluconobacter oxydans is an important Gram-negative industrial microorganism that produces vitamin C and other products due to its efficient membrane-bound dehydrogenase system. Its incomplete oxidation system has many crucial industrial applications. However, it also leads to slow growth and low biomass, requiring further metabolic modification for balancing the cell growth and incomplete oxidation process. As a non-model strain, G. oxydans lacks efficient genome editing tools and cannot perform rapid multi-gene editing and complex metabolic network regulation. In the last 15 years, our laboratory attempted to deploy multiple CRISPR/Cas systems in different G. oxydans strains and found none of them as functional. In this study, Cpf1-based or dCpf1-based CRISPRi was constructed to explore the targeted binding ability of Cpf1, while Cpf1-FokI was deployed to study its nuclease activity. A study on Cpf1 found that the CRISPR/Cpf1 system could locate the target genes in G. oxydans but lacked the nuclease cleavage activity. Therefore, the CRISPR/Cpf1-FokI system based on FokI nuclease was constructed. Single-gene knockout with efficiency up to 100% and double-gene iterative editing were achieved in G. oxydans. Using this system, AcrVA6, the anti-CRISPR protein of G. oxydans was discovered for the first time, and efficient genome editing was realized.

Novel 4th-generation phytase improves broiler growth performance and reduces woody breast severity through modulation of muscle glucose uptake and metabolism.

The objective of the present study was to determine the effect of a novel (4th generation) phytase supplementation as well as its mode of action on growth, meat quality, and incidence of muscle myopathies. One-day old male broilers (n = 720) were weighed and randomly allocated to 30 floor pens (24 birds/pen) with 10 replicate pens per treatment. Three diets were fed from hatch to 56- days-old: a 3-phase corn-soy based diet as a positive control (PC); a negative control (NC) formulated to be isocaloric and isonitrogenous to the PC and with a reduction in Ca and available P, respectively; and the NC supplemented with 2,000 phytase units per kg of diet (NC + P). At the conclusion of the experiment, birds fed with NC + P diet were significantly heavier and had 2.1- and 4.2-points better feed conversion ratio (FCR) compared to birds offered NC and PC diets, respectively. Processing data showed that phytase supplementation increased live weight, hot carcass without giblets, wings, tender, and skin-on drum and thigh compared to both NC and PC diets. Macroscopic scoring showed that birds fed the NC + P diet had lower woody breast (WB) severity compared to those fed the PC and NC diets, however there was no effect on white striping (WS) incidence and meat quality parameters (pH, drip loss, meat color). To delineate its mode of action, iSTAT showed that blood glucose concentrations were significantly lower in birds fed NC + P diet compared to those offered PC and NC diets, suggesting a better glucose uptake. In support, molecular analyses demonstrated that the breast muscle expression (mRNA and protein) of glucose transporter 1 (GLUT1) and glucokinase (GK) was significantly upregulated in birds fed NC + P diet compared to those fed the NC and PC diets. The expression of mitochondrial ATP synthase F0 subunit 8 (MT-ATP8) was significantly upregulated in NC + P compared to other groups, indicating intracellular ATP abundance for anabolic pathways. This was confirmed by the reduced level of phosphorylated-AMP-activated protein kinase (AMPKα1/2) at Thr172 site, upregulation of glycogen synthase (GYS1) gene and activation of mechanistic target of rapamycin and ribosomal protein S6 kinase (mTOR-P70S6K) pathway. In conclusion, this is the first report showing that in-feed supplementation of the novel phytase improves growth performance and reduces WB severity in broilers potentially through enhancement of glucose uptake, glycolysis, and intracellular ATP production, which used for muscle glycogenesis and protein synthesis.

Comparison of Skeletal Changes in the Temporomandibular Joint between the Twin Block Appliance and Fixed Functional Appliance: A Longitudinal Follow-up Study.

Aim: This current study evaluated and compared the skeletal changes in the head of the condyle, glenoid fossa, and articular space between the twin block appliance and PowerScope™ a fixed functional appliance. Materials and methods: This study was a pilot, randomized, single-blinded, assessing the skeletal changes in the components of the temporomandibular joint (TMJ) using cone-beam computed tomography (CBCT). The study was conducted in 20 subjects in the age range of 11-14 years with class II division 1 malocclusion. These subjects were distributed randomly between two groups with an allocation ratio of 1:1 (group I-twin block and group I-PowerScope™). Follow-ups of both groups were done till desirable skeletal correction was attained (clinical edge-to-edge incisor relation). Results: Condylar parameters such as position, height, and length were evaluated bilaterally in the CBCT scans. After using both devices, there was an increase in all condylar qualities; however, the twin block appliance showed a more noticeable difference, which has been determined to be statistically significant. In the twin block group, there was an average decrease of 0.56 mm in the anterior articular space and an increase of 1.2 and 2.64 mm in the middle and posterior articular spaces, respectively. In the PowerScope™ group, there was an average decrease of 0.23 mm in the anterior articular space and an increase of 2.55 and 1.85 mm in the middle and posterior articular spaces, respectively. In the case of the twin block device, the change in glenoid fossa angle was observed to be 6.1 mm on both sides and a mean difference of 1.25 mm on the right-side and 1.75 mm on the left-side was observed in the case of PowerScope™. The difference was established to be significant with a p < 0.05 in all cases. Conclusion: Condylar attributes increased after the application of both devices but the difference was more pronounced in the case of twin block appliances. The difference in articular space (middle and posterior) between the twin block group and PowerScope™ group, was not significant statistically. In the present study, the remodeling in the glenoid fossa was greater in the twin block group compared to the PowerScope™ group. How to cite this article: Halapanavar B, MN P, Deshmukh S, et al. Comparison of Skeletal Changes in the Temporomandibular Joint between the Twin Block Appliance and Fixed Functional Appliance: A Longitudinal Follow-up Study. Int J Clin Pediatr Dent 2024;17(1):7-14.

Evaluation of the modulating effect of epidermal growth factor receptor inhibitor cetuximab in carbon-tetrachloride induce hepatic fibrosis in rats.

Liver fibrosis, developed in almost all chronic liver injuries. Epidermal growth factor receptors (EGFR) have been thought to contribute to cirrhosis and liver fibrosis. Therefore, using a rat model of carbon tetrachloride (CCl4)-induced liver fibrogenesis, we investigated the preventive effects of cetuximab, an inhibitor of the EGF receptor (EGFR). Ameliorative effects of cetuximab were examined in rats, brought on by biweekly doses of 50 mg/kg of carbon tetrachloride (CCl4). There were a total of 24 male Long Evans rats split up into four distinct groups such as control, CCl4, control+cetuximab and CCl4+cetuximab. After two weeks of treatment with cetuximab (100 µg/kg), samples of tissue and blood were taken after all the rats had been sacrificed. Plasma samples were examined for the biochemical indicators of inflammation and oxidative stress. Histological staining on liver sections was performed for morphologic pathologies, and related genes expressions analysis were done with RT-PCR in liver tissue. The findings showed that cetuximab could raise the levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) and considerably lower the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), and nitric oxide (NO). Sirius red staining and hematoxylin-eosin (H&E) displayed that cetuximab therapy reduced the inflammatory cells infiltration and enhanced fibrotic lesions. In the meantime, cetuximab therapy also dramatically reduces the expression of genes linked to inflammation in the liver tissue, including NF-кB, iNOS, IL-6, TNF-α, and TGF-ß. To sum up, the anti-inflammatory, antifibrotic, and antioxidant properties of cetuximab confer curative efficacy against liver fibrosis.

Dietary zinc requirement of juvenile stinging catfish Heteropneustes fossilis based on growth performance, haematology, and tissue mineral composition.

This investigation was done to determine how much zinc (Zn) the stinging catfish, Heteropneustes fossilis, needs in its diet. Five isonitrogenous (34.5% protein) and isolipidic (6.0% lipid) diets were prepared to contain graded levels of Zn (0, 10, 20, 30, and 40 mg kg-1), supplied as zinc sulfate (ZnSO4·7H2O), and referred to as Zn0, Zn10, Zn20, Zn30, and Zn40, respectively. A total of 600 fish (initial body weight: 1.41 ± 0.02 g) were stocked in 15 glass aquaria (40 fish/aquarium), each with 180 L water capacity. For ten weeks, each diet was hand fed to three groups of fish twice daily until they appeared satisfied. The highest weight gain and specific growth rate, and lowest feed conversion ratio were recorded in fish fed with a 30 mg Zn kg-1 diet. Zn contents in bone and muscle linearly increased up to 30 mg kg-1 Zn and then remained stable, while iron (Fe) and copper (Cu) contents in bone and muscle had an inverse pattern with the inclusion level of dietary Zn. Increasing dietary Zn levels up to 30 mg kg-1 was found to improve values of hematological parameters such as red blood cell (RBC), white blood cell (WBC), haemoglobin (Hb), and haematocrit (HCT). These values, however, decreased when the dietary Zn level was further increased. The serum alkaline phosphatase level was the highest in fish fed a diet containing 30 mg kg-1 of Zn. Regression analyses based on weight gain, specific growth rate, and bone and muscle Zn concentrations indicated that the optimum dietary Zn requirement for stinging catfish was in a range of 27.4-36.5 mg kg-1.

Elevation-dependent tree growth response to climate in a natural Scots pine/downy birch forest in northern Sweden.

Forests dominate the landscape at high latitudes in the boreal regions and contribute significantly to the global carbon stock. Large areas are protected and provide possibilities to analyze natural forest dynamics including resilience to climate change. In Fennoscandia, Scots pine (Pinus sylvestris L.) and downy birch (Betula pubescens Ehrh.) often coexist in natural forests close to the limits of their ecological ranges. Tree growth in these forests is generally thought to be limited by temperature, and changes in growth trends can therefore serve as early indicators of the impact of global warming on natural ecosystems. We sampled 592 Scots pine and downy birch trees along two elevational gradients spanning the transition from the forest zone to the coniferous treeline in Tjeggelvas nature reserve, northern Sweden. Based on the tree-ring data, we compared annual basal area increment (BAI) trends from 1902 to 2021, analyzed the ring-width indices (RWI) in relation to local climate data, and investigated trends in climate-growth relationships. We found that the mean annual growth of both species was higher in more recent years than at the beginning of the 20th century. The RWI were positively correlated with summer temperatures, however, we found a much stronger relationship for Scots pine than downy birch. We noticed a decrease in the importance of summer temperature for Scots pine growth, whereas the importance of late spring temperatures increased over the 120-year-long study period. Due to strongly positive BAI trends combined with a decrease in temperature sensitivity, the overall conclusion of our study is that the influence of increasing temperatures is still positive and outweighs the negative impacts of climate change on Scots pine growth in natural forests in northern Sweden, particularly at higher elevations. Natural forests are important natural experiments that contrast the managed forests and are key to understanding the latter.

Serratia spp. as plant growth-promoting bacteria alleviating salinity, drought, and nutrient imbalance stresses.

In agricultural environments, plants are often exposed to abiotic stresses including temperature extremes, salt stress, drought, and heavy metal soil contamination, which leads to significant economic losses worldwide. Especially salt stress and drought pose serious challenges since they induce ionic toxicity, osmotic stress, and oxidative stress in plants. A potential solution can be the application of bacteria of the Serratia spp. known to promote plant growth under normal conditions Thus the mini-review aims to summarize the current knowledge on plant growth promotion by Serratia spp. (under the conditions of salinity stress, drought, and nutrient deficit) and highlight areas for development in the field. So far, it has been proven that Serratia spp. strains exhibit a variety of traits contributing to enhanced plant growth and stress tolerance, such as phytohormone production, ACC deaminase activity, nitrogen fixation, P and Zn solubilization, antioxidant properties improvement, and modulation of gene expression. Nevertheless, further research on Serratia spp. is needed, especially on two subjects: elucidating its mechanisms of action on plants at the molecular level and the effects of Serratia spp. on the indigenous soil and plant microbiota and, particularly, the rhizosphere. In both cases, it is advisable to use omics techniques to gain in-depth insights into the issues. Additionally, some strains of Serratia spp. may be phytopathogens, therefore studies to rule out this possibility are recommended prior to field trials. It is believed that by improving said knowledge the potential of Serratia spp. to stimulate plant growth will increase and strains from the genus will serve as an eco-friendly biofertilizer in sustainable agriculture more often.

MicroRNA-155 mediates multiple gene regulations pertinent to the role of human adipose-derived mesenchymal stem cells in skin regeneration.

Introduction: The role of Adipose-derived mesenchymal stem cells (AD-MSCs) in skin wound healing remains to be fully characterized. This study aims to evaluate the regenerative potential of autologous AD-MSCs in a non-healing porcine wound model, in addition to elucidate key miRNA-mediated epigenetic regulations that underlie the regenerative potential of AD-MSCs in wounds. Methods: The regenerative potential of autologous AD-MSCs was evaluated in porcine model using histopathology and spatial frequency domain imaging. Then, the correlations between miRNAs and proteins of AD-MSCs were evaluated using an integration analysis in primary human AD-MSCs in comparison to primary human keratinocytes. Transfection study of AD-MSCs was conducted to validate the bioinformatics data. Results: Autologous porcine AD-MSCs improved wound epithelialization and skin properties in comparison to control wounds. We identified 26 proteins upregulated in human AD-MSCs, including growth and angiogenic factors, chemokines and inflammatory cytokines. Pathway enrichment analysis highlighted cell signalling-associated pathways and immunomodulatory pathways. miRNA-target modelling revealed regulations related to genes encoding for 16 upregulated proteins. miR-155-5p was predicted to regulate Fibroblast growth factor 2 and 7, C-C motif chemokine ligand 2 and Vascular cell adhesion molecule 1. Transfecting human AD-MSCs cell line with anti-miR-155 showed transient gene silencing of the four proteins at 24 h post-transfection. Discussion: This study proposes a positive miR-155-mediated gene regulation of key factors involved in wound healing. The study represents a promising approach for miRNA-based and cell-free regenerative treatment for difficult-to-heal wounds. The therapeutic potential of miR-155 and its identified targets should be further explored in-vivo.

Lower serum insulin-like growth factor 2 level in patients with bipolar disorder is associated with the severity of manic symptoms during manic episodes.

Objective: Accumulating evidence has indicated that neurodevelopmental defects may underlie the pathophysiology of bipolar disorder (BD). Insulin-like growth factors (IGFs) are a family of neurotrophic factors that are essential for the survival and development of neurons. The present study aims to investigate whether IGF-2 signaling is implicated in the pathophysiological processes of BD. Method: 50 healthy controls and 78 patients with BD, including 23 patients who diagnosed acute depressive episode and 55 patients who diagnosed acute manic episode, were recruited in this study. The 17-item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale (YMRS) were used to assess the severity of the depressive and manic symptoms, respectively. The serum IGF-2 level was determined by an enzyme-linked immunosorbent assay (ELISA). The Kolmogorov-Smirnov and Mann-Whitney U tests were used for between-group comparisons and spearman analysis was used to analyze correlations. Results: Patients with BD had lower serum IGF-2 levels (66.08 ± 21.22 ng/ml) when compared to healthy controls (88.72 ± 31.55 ng/ml). BD patients were divided into manic episode and depressive episode subgroups. We found that serum IGF-2 levels were reduced in both the mania and depression subgroups (mania: 67.19 ± 21.52 ng/ml, depression: 63.43 ± 20.67 ng/ml; P < 0.001), while no significant difference was observed between two groups (P > 0.05). Spearman correlation analyses revealed that the levels of serum IGF-2 were negatively correlated with the YMRS scores in BD patients (r = -0.522, P < 0.001). Furthermore, IGF-2 was found to be an independent contributor to the severity of symptoms in patients with manic episodes (B = -0.610, t = -5.299, P < 0.001). Conclusion: Lower serum IGF-2 levels were found in BD patients and correlated with the severity of the manic symptoms in these patients during manic episodes. These results suggest that reduced IGF-2 levels might be involved in the pathophysiology of BD, and serum IGF-2 could be a peripheral biomarker for the evaluation of the severity of manic symptoms in BD patients.

Dynamic simulation and projection of ESV changes in arid regions caused by urban growth under climate change scenarios.

Spatial simulation and projection of ecosystem services value (ESV) changes caused by urban growth are important for sustainable development in arid regions. We developed a new model of cellular automata based grasshopper optimization algorithm (named GOA-CA) for simulating urban growth patterns and assessing the impacts of urban growth on ESV changes under climate change scenarios. The results show that GOA-CA yielded overall accuracy exceeding 98%, and FOM for 2010 and 2020 were 43.2% and 38.1%, respectively, indicating the effectiveness of the model. The prairie lost the highest economic ESVs (192 million USD) and the coniferous yielded the largest economic ESV increase (292 million USD) during 2000-2020. Using climate change scenarios as urban future land use demands, we projected three scenarios of the urban growth of Urumqi for 2050 and their impacts on ESV. Our model can be easily applied to simulating urban development, analyzing its impact on ESV and projecting future scenarios in global arid regions.

IGF2 promotes alveolar bone regeneration in murine periodontitis via inhibiting cGAS/STING-mediated M1 macrophage polarization.

Periodontitis is a chronic inflammatory disease with the destruction of supporting periodontal tissue. This study evaluated the role of insulin-like growth factor 2 (IGF2) in periodontitis by inhibiting the polarization of M1 macrophages via the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway. IGF2 was enriched in the gingival tissue of murine periodontitis model identified by RNA sequencing. IGF2 application alleviated the expression of pro-inflammatory factors and promoted osteogenesis and the expression of related genes and proteins in a dose-dependent manner in periodontitis. The result of micro-CT verified this finding. Both in vivo and in vitro results revealed that IGF2 decreased the polarization of M1 macrophages and pro-inflammatory factors by immunofluorescence staining, flow cytometry, western blotting and RT-PCR. IGF2 application promoted the osteogenic ability of periodontal ligament fibroblasts (PDLFs) indirectly via its inhibition of M1 polarization evaluated by alkaline phosphatase and alizarin red staining. Then, the cGAS/STING pathway was upregulated in periodontitis and macrophages challenged by LPS, the inhibition of which led to downregulation of M1 polarization. Furthermore, IGF2 could downregulate cGAS, STING and the phosphorylation of P65. Collectively, our study indicates IGF2 can regulate the polarization of M1 macrophages via the cGAS/STING pathway and highlights the promising future of IGF2 as a therapeutic treatment for periodontitis.

Pilose antler extract promotes hair growth in androgenic alopecia mice by promoting the initial anagen phase.

Androgenetic alopecia (AGA) is a prevalent disease in worldwide, local application or oral are often used to treat AGA, however, effective treatments for AGA are currently limited. In this work, we observed the promoting the initial anagen phase effect of pilose antler extract (PAE) on hair regeneration in AGA mice. We found that PAE accelerated hair growth and increased the degree of skin blackness by non-invasive in vivo methods including camera, optical coherence tomography and dermoscopy. Meanwhile, HE staining of sagittal and coronal skin sections revealed that PAE augmented the quantity and length of hair follicles, while also enhancing skin thickness and hair papilla diameter. Furthermore, PAE facilitated the shift of the growth cycle from the telogen to the anagen phase and expedited the proliferation of hair follicle stem cells and matrix cells in mice with AGA. This acceleration enabled the hair follicles to enter the growth phase at an earlier stage. PAE upregulated the expression of the sonic hedgehog (SHH), smoothened receptor, glioma-associated hemolog1 (GLI1), and downregulated the expression of bone morphogenetic protein 4 (BMP4), recombinant mothers against decapentaplegic homolog (Smad) 1 and 5 phosphorylation. This evidence suggests that PAE fosters hair growth and facilitates the transition of the growth cycle from the telogen to the anagen phase in AGA mice. This effect is achieved by enhancing the proliferation of follicle stem cells and matrix cells through the activation of the SHH/GLI pathway and suppression of the BMP/Smad pathway.

Implementation of antibody-drug conjugates in HER2-positive solid cancers: Recent advances and future directions.

In recent decades, there has been a surge in the approval of monoclonal antibodies for treating a wide range of hematological and solid malignancies. These antibodies exhibit exceptional precision in targeting the surface antigens of tumors, heralding a groundbreaking approach to cancer therapy. Nevertheless, monoclonal antibodies alone do not show sufficient lethality against cancerous cells compared to chemotherapy. Consequently, a new class of anti-tumor medications, known as antibody-drug conjugates (ADCs), has been developed to bridge the divide between monoclonal antibodies and cytotoxic drugs, enhancing their therapeutic potential. ADCs are chemically synthesized by binding tumor-targeting monoclonal antibodies with cytotoxic payloads through linkers that are susceptible to cleavage by intracellular proteases. They combined the accurate targeting of monoclonal antibodies with the potent efficacy of cytotoxic chemotherapy drugs while circumventing systemic toxicity and boasting superior lethality over standalone targeted drugs. The human epidermal growth factor receptor (HER) family, which encompasses HER1 (also known as EGFR), HER2, HER3, and HER4, plays a key role in regulating cellular proliferation, survival, differentiation, and migration. HER2 overexpression in various tumors is one of the most frequently targeted antigens for ADC therapy in HER2-positive cancers. HER2-directed ADCs have emerged as highly promising treatment modalities for patients with HER2-positive cancers. This review focuses on three approved anti-HER2 ADCs (T-DM1, DS-8201a, and RC48) and reviews ongoing clinical trials and failed trials based on anti-HER2 ADCs. Finally, we address the notable challenges linked to ADC development and underscore potential future avenues for tackling these hurdles.

Knockout of endoplasmic reticulum-localized molecular chaperone HSP90.7 impairs seedling development and cellular auxin homeostasis in Arabidopsis.

The Arabidopsis endoplasmic reticulum-localized heat shock protein HSP90.7 modulates tissue differentiation and stress responses; however, complete knockout lines have not been previously reported. In this study, we identified and analyzed a mutant allele, hsp90.7-1, which was unable to accumulate the HSP90.7 full-length protein and showed seedling lethality. Microscopic analyses revealed its essential role in male and female fertility, trichomes and root hair development, proper chloroplast function, and apical meristem maintenance and differentiation. Comparative transcriptome and proteome analyses also revealed the role of the protein in a multitude of cellular processes. Particularly, the auxin-responsive pathway was specifically downregulated in the hsp90.7-1 mutant seedlings. We measured a much-reduced auxin content in both root and shoot tissues. Through comprehensive histological and molecular analyses, we confirmed PIN1 and PIN5 accumulations were dependent on the HSP90 function, and the TAA-YUCCA primary auxin biosynthesis pathway was also downregulated in the mutant seedlings. This study therefore not only fulfilled a gap in understanding the essential role of HSP90 paralogs in eukaryotes but also provided a mechanistic insight on the ER-localized chaperone in regulating plant growth and development via modulating cellular auxin homeostasis.