Identification of necroptosis-related genes in ankylosing spondylitis by bioinformatics and experimental validation.

The pathogenesis of ankylosing spondylitis (AS) remains unclear, and while recent studies have implicated necroptosis in various autoimmune diseases, an investigation of its relationship with AS has not been reported. In this study, we utilized the Gene Expression Omnibus database to compare gene expressions between AS patients and healthy controls, identifying 18 differentially expressed necroptosis-related genes (DENRGs), with 8 upregulated and 10 downregulated. Through the application of three machine learning algorithms-least absolute shrinkage and selection operation, support vector machine-recursive feature elimination and random forest-two hub genes, FASLG and TARDBP, were pinpointed. These genes demonstrated high specificity and sensitivity for AS diagnosis, as evidenced by receiver operating characteristic curve analysis. These findings were further supported by external datasets and cellular experiments, which confirmed the downregulation of FASLG and upregulation of TARDBP in AS patients. Immune cell infiltration analysis suggested that CD4+ T cells, CD8+ T cells, NK cells and neutrophils may be associated with the development of AS. Notably, in the group with high FASLG expression, there was a significant infiltration of CD8+ T cells, memory-activated CD4+ T cells and resting NK cells, with relatively less infiltration of memory-resting CD4+ T cells and neutrophils. Conversely, in the group with high TARDBP expression, there was enhanced infiltration of naïve CD4+ T cells and M0 macrophages, with a reduced presence of memory-resting CD4+ T cells. In summary, FASLG and TARDBP may contribute to AS pathogenesis by regulating the immune microenvironment and immune-related signalling pathways. These findings offer new insights into the molecular mechanisms of AS and suggest potential new targets for therapeutic strategies.

The genetic causal relationship between type 2 diabetes, glycemic traits and venous thromboembolism, deep vein thrombosis, pulmonary embolism: a two-sample Mendelian randomization study.

OBJECTIVE: To investigate the genetic underpinnings of the association between type 2 diabetes (T2D), glycemic indicators such as fasting glucose (FG), fasting insulin (FI), and glycated hemoglobin (GH), and venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), thereby contributing novel insights to the scholarly discourse within this domain. METHODS: Genome-wide association study (GWAS) summary data pertaining to exposures (T2D, FG, FI, GH) and outcomes (VTE, DVT, PE) were acquired from the IEU Open GWAS database, encompassing participants of European descent, including both male and female individuals. Two-sample Mendelian randomization (MR) analyses were conducted utilizing the TwoSampleMR and MRPRESSO packages within the R programming environment. The primary analytical approach employed was the random-effects inverse variance weighted (IVW) method. Heterogeneity was assessed via Cochran's Q statistic for MR-IVW and Rucker's Q statistic for MR-Egger. Horizontal pleiotropy was evaluated using the intercept test of MR Egger and MR pleiotropy residual sum and outlier (MR-PRESSO) analysis, with the latter also employed for outlier detection. Additionally, a "Leave one out" analysis was conducted to ascertain the influence of individual single nucleotide polymorphisms (SNPs) on MR results. RESULTS: The random-effects IVW analysis revealed a negative genetic causal association between T2D) and VTE (P = 0.008, Odds Ratio [OR] 95% confidence interval [CI] = 0.896 [0.827-0.972]), as well as between FG and VTE (P = 0.002, OR 95% CI = 0.655 [0.503-0.853]), GH and VTE (P = 0.010, OR 95% CI = 0.604 [0.412-0.884]), and GH and DVT (P = 0.002, OR 95% CI = 0.413 [0.235-0.725]). Conversely, the random-effects IVW analysis did not detect a genetic causal relationship between FI and VTE (P > 0.05), nor between T2D, FG, or FI and DVT (P > 0.05), or between T2D, FG, FI, or GH and PE (P > 0.05). Both the Cochran's Q statistic for MR-IVW and Rucker's Q statistic for MR-Egger indicated no significant heterogeneity (P > 0.05). Moreover, the intercept tests of MR Egger and MR-PRESSO suggested the absence of horizontal pleiotropy (P > 0.05). MR-PRESSO analysis identified no outliers, while the "Leave one out" analysis underscored that the MR analysis was not influenced by any single SNP. CONCLUSION: Our investigation revealed that T2D, FG, and GH exhibit negative genetic causal relationships with VTE at the genetic level, while GH demonstrates a negative genetic causal relationship with DVT at the genetic level. These findings furnish genetic-level evidence warranting further examination of VTE, DVT, and PE, thereby making a contribution to the advancement of related research domains.

Characterization and Functional Analysis of Chalcone Synthase Genes in Highbush Blueberry (Vaccinium corymbosum).

Chalcone synthase (CHS) is the first key enzyme-catalyzing plant flavonoid biosynthesis. Until now, however, the blueberry CHS gene family has not been systematically characterized and studied. In this study, we identified 22 CHS genes that could be further classified into four subfamilies from the highbush blueberry (Vaccinium corymbosum) genome. This classification was well supported by the high nucleotide and protein sequence similarities and similar gene structure and conserved motifs among VcCHS members from the same subfamily. Gene duplication analysis revealed that the expansion of the blueberry CHS gene family was mainly caused by segmental duplications. Promoter analysis revealed that the promoter regions of VcCHSs contained numerous cis-acting elements responsive to light, phytohormone and stress, along with binding sites for 36 different types of transcription factors. Gene expression analysis revealed that Subfamily I VcCHSs highly expressed in fruits at late ripening stages. Through transient overexpression, we found that three VcCHSs (VcCHS13 from subfamily II; VcCHS8 and VcCHS21 from subfamily I) could significantly enhance the anthocyanin accumulation and up-regulate the expression of flavonoid biosynthetic structural genes in blueberry leaves and apple fruits. Notably, the promoting effect of the Subfamily I member VcCHS21 was the best. The promoter of VcCHS21 contains a G-box (CACGTG) and an E-box sequence, as well as a bHLH binding site. A yeast one hybridization (Y1H) assay revealed that three anthocyanin biosynthesis regulatory bHLHs (VcAN1, VcbHLH1-1 and VcbHLH1-2) could specifically bind to the G-box sequence (CACGTG) in the VcCHS21 promoter, indicating that the expression of VcCHS21 was regulated by bHLHs. Our study will be helpful for understanding the characteristics and functions of blueberry CHSs.

Optimizing irrigation strategies for sustainable crop productivity and reduced groundwater consumption in a winter wheat-maize rotation system.

Inefficient irrigation practices have hindered crop yields, wasted irrigation water resources, and posed threats to groundwater levels and agricultural sustainability. This study evaluated different irrigation strategies for a winter wheat-summer maize rotation system to identify sustainable practices for maintaining yields while reducing groundwater depletion. A two-year field experiment was conducted, implementing three optimized irrigation strategies during the winter wheat season: I-4 (irrigated until the soil water content (SWC) of the 40 cm soil layer reaches 60% of field capacity (FC), I-6 (irrigated until the SWC of the 60 cm soil layer reaches 80% FC), and a rainfed (R) as control. Irrigation was repeated when the SWC dropped to the specified level. No irrigation level was used during the summer maize season, except for irrigation after sowing that ensuring the normal emergence of maize. WHCNS (Water Heat Carbon Nitrogen Simulator) model was developed to simulate soil water dynamics, field water consumption, and yield of both crops. The result indicated WHCNS model accurately simulated water dynamics, consumption, and grain yield. Compared to R treatment, the I-4 treatment significantly increased annual crop yield by 19.83%-28.65% (p < 0.05), while maintaining similar crop water productivity. Furthermore, the I-4 treatment achieved comparable yields to the I-6 treatment, but with a 33.91% reduction in irrigation water use, resulting in a 33.46% increase in crop water productivity and a 90.53% increase in irrigation water productivity. From a sustainable perspective, the I-4 treatment effectively reduced field water losses and maintained relatively high soil water storage, particularly in the topsoil, which was beneficial for the early growth of subsequent crops. The R treatment greatly contributed to groundwater recharge when precipitation was sufficient, while it led to severe yield losses. Overall, under the condition of annual rotation planting systems, the I-4 treatment sustainably maintained yields with less irrigation, decreasing groundwater consumption. This approach could conserve regional water resources and groundwater table while upholding agricultural productivity and achieving system sustainable water use.

The effect of the necrotic area on the biomechanics of the femoral head - a finite element study.

BACKGROUND: Femoral head collapse is the key to the progress of osteonecrosis of the femoral head (ONFH), but the causes of collapse are not completely clear. The better understanding of the progress of femoral head collapse will guide the treatment strategy for ONFH patients. The purpose of this study was to evaluate the biomechanical influence of necrosis area on the collapse of the femoral head by finite element analysis. METHODS: CT and MRI data from the hip joint of a healthy volunteer were collected to establish a finite element (FE) model of a normal hip. Subsequently, five categories of osteonecrosis FE models were established by using the normal model and computer software according to China-Japan Friendship Hospital (CJFH) classification for ONFH. The CJFH system includes five types based on the size and location of necrosis lesions in the femoral head (type M, C, L1, L2, and L3) and the stage of ONFH. The collapse indices of each model were analyzed by FE method, including the displacement, peak von Mises stress and stress index of the simulated necrotic area as well as the lateral pillar contact area of the femoral head to acetabular. RESULTS: (1) The displacement increments in the simulated necrotic areas of type M, C, L1, L2, and L3 models were 3.75 µm, 8.24 µm, 8.47 µm, 18.42 µm, and 20.44 µm respectively; the peak von Mises stress decrements were 1.50 MPa, 3.74 MPa, 3.73 MPa, 4.91 MPa, and 4.92 MPa respectively; and the stress indices were 0.04, 0.08, 0.08, 0.27, and 0.27 respectively. (2) The displacement increments in the lateral pillar contact areas of five type models were significantly different (P < 0.001) and increased in sequence as follows: 1.93 ± 0.15 µm, 5.74 ± 0.92 µm, 5.84 ± 1.42 µm, 14.50 ± 3.00 µm, and 16.43 ± 3.05 µm. The peak von Mises stress decrements were also significantly different (P < 0.001) and increased in sequence as follows: 0.52 ± 0.30 MPa, 0.55 ± 0.12 MPa, 0.67 ± 0.33 MPa, 4.17 ± 0.59 MPa, and 4.19 ± 0.60 MPa. (3) The collapse indices including the displacement increments and peak von Mises stress decrements of type L2 and L3 models were markedly higher than those of type M, C, and L1 models (P < 0.001). CONCLUSIONS: The collapse indices of the femoral heads of type L2 and L3 FE models were significantly higher than those of type M, C, and L1. Different areas of necrosis result in varied impact on the femoral head collapse.

Comparative Study of the Clinical Pathology, Immunophenotype, Epstein-Barr Virus Infection Status, and Gene Rearrangements in Adult and Child Patients With Hydroa Vacciniforme-Like Lymphoproliferative Disorder.

BACKGROUND: Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) is a rare Epstein-Barr virus (EBV)-associated lymphoma that mainly affects children. OBJECTIVES: To examine the similarities and differences in the clinical pathological features, EBV infection status, and gene rearrangements in adults and children patients with HVLPD. METHODS: We compared the clinical manifestations, histopathology, immunophenotypical features, EBV infection status, and T-cell receptor gene rearrangements in the adult and children HVLPD groups. RESULTS: Clinical manifestations differed between children and adults groups. The children were characterized by blisters and severe facial swelling, whereas the adults were characterized by mild facial swelling and papules. Mosquito bite was significantly related to morbidity in the children group. Histologically, the number of mast cells in the adult group was greater than in the children group (P < 0.05). There were no significant differences in EBV infection status or TCR-γ gene rearrangements between 2 groups. CONCLUSIONS: There were differences in clinical pathology and prognosis between the 2 groups. A higher mast cell count and T-cell phenotype might be associated with a poor prognosis.

[Clinical Comparative Analysis of Lupus Panniculitis and Subcutaneous Panniculitis-like T-cell Lymphoma].

OBJECTIVE: To explore the similarities and differences in clinical pathological features and gene rearrangement of lupus erythematosus profundus(LEP) and subcutaneous panniculitis-like T-cell lymphoma(SPTL). METHODS: We compared the clinical presentations, histopathology, immunophenotypical features and T-cell receptor (TCR) gene rearrangement findings of 9 cases of LEP and SPTL. RESULTS: For clinical features, most patients of LEP occurred on head and face without systemic symptoms. LEP patients responded well to hydroxycholorquine treatment with good prognosis. Most patients of SPTL tended to lower extremities involvement and accompanied with systemic symptoms, the patients with disseminated lesions or hemophagocytic syndrome(HPS) showed poorer prognosis. For histopathology, LEP patients showed dense inflammatory infiltrate in the dermis consisting predominantly of lymphocytes with less numbers of plasma cells. However, the dermis was spared in SPTL, and rimming of adipocytes and erythrophagocytosis was observed in SPTL. Lymphocytes of LEP expressing CD4+/CD8+, as well as clusters of CD20+. CD138-positive cells and scatter of CD123-positive cells were also observed in LEP. Tumor cells of SPTL were CD4-/CD8+, ßF1+, CD138- and CD123-. The expression of TIA-1 or GrB was more favor in SPTL. Monoclonal T-cell receptor-γ gene rearrangement was found in 89% of SPTL patients while negative for LEP. CONCLUSION: Base on different clinical and pathological features, it is easy to distinguish LEP from SPTL. However, a minority of lesions in LEP localize at subcutaneous tissue, which may turn to immunophenotypical and TCR gene rearrangement test for diagnosis.

[Investigate the clonal origin of different phenotypic tumor-like cells in the epidermis and dermis of skin lesions in lymphomatoid papulosis].

OBJECTIVE: To explore the correlation of the clone sources of MF-like cells in the epidermis and RS-like cells in the dermis of lymphomatoid papulosis (LyP), a compartive study of this two type cells in 8 LyP cases was carried out. METHODS: 8 cases of LyP (4 type A cases and 4 type C cases) were detected the immunophenotype first, and then comparative study between the MF-like cells and RS-like cells was conducted on T-cell receptor (TCR) gamma-chain gene rearrangement by combinating laser capture microdissectinon (LCM) and PCR. PCR products of one patient which had positive bands were selected randomly for sequencing and sequence alignment analysis. RESULTS: Monoclonal TCRgamma gene rearrangement was detected in 6 cases (75%) of the 8 cases. Detection rates of LyP type A and type C were 50% (2/4) and 100% (4/4), respectively. The rates of MF-like cells and RS-like cells were 75% (6/8) and 75% (6/8), respectively. Homology of the products with positive stripes in both MF-like cells and RS-like cells in one randomly selected case was compared and analyzed, and the results showed the homology of them was 106/108 (98%). CONCLUSION: The MF-like cells in the epidermis and the RS-like cells in the dermis of LyP may be from the same clone.

CTLA-4 CT60 (rs3087243) polymorphism and autoimmune thyroid diseases susceptibility: a comprehensive meta-analysis.

OBJECTIVE: To determine whether the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) CT60 polymorphism (rs3087243) confers susceptibility to autoimmune thyroid disease (AITDs). METHODS: A meta-analysis was performed using: (1) allelic contrast, (2) recessive model and (3) dominant model. Electronic search of PubMed, Medline and Chinese National Knowledge Infrastructure (CNKI) was conducted to select studies. RESULTS: Finally, a total of 20 separate studies were available for the current meta-analysis: Graves' disease (GD): 18 studies including 1 Iranian, 6 Caucasian and 11 Asian populations; Hashimoto's thyroiditis (HT): seven studies including one Iranian, three Caucasian and three Asian populations. A significant association was found between the CTLA-4 CT60 polymorphism (rs3087243) and GD, with regard to comparisons between allele and genotype frequencies (all p < 0.001). After stratification by ethnicity, significant relationships were consistently identified both in Caucasian and Asian populations. Furthermore, the association between this allelic variant and HT risk was also found in overall and Asian populations (OR: 1.26, 95% CI: 1.10-1.44; OR: 1.45, 95% CI: 1.19-1.76, respectively). CONCLUSION: Taken together, our study suggested that the CT60 polymorphism (rs3087243) in CTLA-4 gene might confer susceptibility to the AITDs (GD/HT).

[Effects of amino acid on growth and secondary metabolites contents of adventitious roots of Tripterygium wilfordii].

The adventitious root of Tripterygium wilfordii was used as experiment material to study effects of various concentration of aspartic acid, isoleucine, cysteine and arginine in MS medium on the growth and triptolide, wilforgine, wilforine contents of the adventitious roots. The results showed that compared with the control, supplemented with 0.25 mmol x L(-1) aspartic acid at 3rd week, the growth of the adventitious roots only accounted for 80%, but the content of triptolide of the adventitious roots and the medium was 1.36, 1.30 times, the content of wilforgine was 1.16, 1.37 times, the content of wilforine was 1.22, 1.63 times, respectively. At 3rd week 0.05 mmol x L(-1) isoleucine, the growth of adventitious roots was 97.3%, wilforgine of adventitious roots and medium 1.02, 1.27 times, wilforine 1.36 times and 1.15 times. At 1st week 0.25 mmol x L(-1) cysteine, the growth of the adventitious roots comprised 77.5% of the control, while content of triptolide of adventitious roots reached 1.87 times. At 2nd week 1.00 mmol x L(-1) cysteine, the growth of adventitious roots was 44.6% of the control, the content of wilforine in medium was 2.97 times. At 3rd week 0.50 mmol x L(-1) arginine, the growth of adventitious roots was 124.2%, the content of wilforgine and wilforine was 1.3, 1.4 times, respectively.

Effects of selenium and iodine on Kashin-Beck disease: an updated review.

Kashin-Beck disease (KBD) is an endochondral osteogenesis disorder characterised by epiphysis damage and secondary deformable arthropathy induced by multiple external factors, among which selenium (Se) and iodine deficiency are important influencing factors. Iodine deficiency is usually accompanied by a low Se content in the soil in the KBD areas of China. Se can reverse oxidative damage to chondrocytes. In addition, Se is related to the bone conversion rate and bone mineral density. Low Se will hinder growth and change bone metabolism, resulting in a decrease in the bone conversion rate and bone mineral density. Thyroid hormone imbalance caused by thyroid dysfunction caused by iodine deficiency can damage bone homeostasis. Compared with Se deficiency alone, Se combined with iodine deficiency can reduce the activity of glutathione peroxidase more effectively, which increases the vulnerability of chondrocytes and other target cells to oxidative stress, resulting in chondrocyte death. Clinical studies have shown that supplementation with Se and iodine is helpful for the prevention and treatment of KBD.

The role of magnesium in the pathogenesis of osteoporosis.

Magnesium (Mg), a nutritional element which is essential for bone development and mineralization, has a role in the progression of osteoporosis. Osteoporosis is a multifactorial disease characterized by significant deterioration of bone microstructure and bone loss. Mg deficiency can affect bone structure in an indirect way through the two main regulators of calcium homeostasis (parathyroid hormone and vitamin D). In human osteoblasts (OBs), parathyroid hormone regulates the expression of receptor activator of nuclear factor-κ B ligand (RANKL) and osteoprotegerin (OPG) to affect osteoclast (OC) formation. In addition, Mg may also affect the vitamin D3 -mediated bone remodeling activity. vitamin D3 usually coordinates the activation of the OB and OC. The unbalanced activation OC leads to bone resorption. The RANK/RANKL/OPG axis is considered to be a key factor in the molecular mechanism of osteoporosis. Mg participates in the pathogenesis of osteoporosis by affecting the regulation of parathyroid hormone and vitamin D levels to affect the RANK/RANKL/OPG axis. Different factors affecting the axis and enhancing OC function led to bone loss and bone tissue microstructure damage, which leads to the occurrence of osteoporosis. Clinical research has shown that Mg supplementation can alleviate the symptoms of osteoporosis to some extent.

Successful treatment of acrodermatitis continua of Hallopeau coexisting with generalized pustular psoriasis with spesolimab: a case report.

Generalized pustular psoriasis (GPP) is a rare chronic inflammatory pustular dermatosis that presents as painful erythema with sterile pustules on nonacral skin. No unified standard and guideline for the treatment of GPP has been established. Several biologics have been tried for GPP, with varying success. Acrodermatitis continua of Hallopeau (ACH) is a very rare disabling variant of pustular psoriasis characterized by sterile pustules on the fingers and toes, including the nail bed. Comparatively, treating ACH is highly challenging due to its commonly therapy-resistant disease course. The pathogenic role of IL-36 signaling axis has been currently identified in GPP development. Spesolimab, the first anti-interleukin-36 receptor biologic, has been approved for treating GPP flares and shown promising results. In view of a shared pathogenesis between GPP and ACH, specolimab may be an effective treatment for ACH. Currently, there is no case and clinical trial data exist on this condition. Therefore, this case was aim to describe real-world experience of spesolimab use in ACH coexisting with GPP. We report an Asian patient with a 16-year-history of GPP and ACH with marked pustulosis on the nail bed and onychodystrophy. He received conventional systemic regimen acitretin, cyclosporine and biologics adalimumab and secukinumab, but experienced relapse for skin lesions and refractory for nail lesions. He was then treated with a single dose of spesolimab in combination with secukinumab, which resulted in skin clearance and nearly complete resolution of nail lesions over a 32-week period. Our observation suggests that spesolimab should be considered for the treatment of ACH, especially in the patients with intractable nail lesions and concomitant GPP.

Knowledge mapping and research trends on perioperative neurocognitive disorder from 1990 to 2022: a bibliometric analysis.

Introduction: Perioperative neurocognitive disorder (PND) has attracted consistently increasing attention worldwide. However, there are few bibliometric studies that systematically evaluate this field. This study aimed to visualize the knowledge structure and research trends in PND through bibliometrics to help understand the future development of basic and clinical research. Methods: Literature related to PND in Web of Science and PubMed from 1990 to 2022 were collected through keywords retrospectively. Additionally, the source information, citation information, etc. of these publications were extracted. Finally, bibliometric analysis was performed by visualization software and statistical software. Results: There were 2837 articles and reviews in total. An exponential rise in PND-related publications was observed. China had the most publication, followed by the US and Germany. The institution with the most output and citations was Harvard University (149 papers, 8966 citations). The most prominent author was Marcantonio Edward R with 66 publications and 5721 citations. The journal with the highest productivity for PND research was Frontiers in Aging Neuroscience followed by Anesthesia and Analgesia. Keywords were identified as six topics, including postoperative delirium, postoperative neurocognitive disorder, cardiac surgery, anaesthesia, orthopedic surgery, and dementia. According to keyword analysis, the most recent popular keywords in PND research were prevention, older patients, emergence delirium, orthopedic surgery, and dexmedetomidine. Conclusions: Publications on PND are increasing at an alarming rate from 1990 to 2022. Current research and future trends will concentrate on the prevention and treatment of PND, as well as PND associated with orthopedic surgery in older adults.

A causal relationship between hypothyroidism and rheumatoid arthritis, but not hyperthyroidism: evidence from the mendelian randomization study.

OBJECTIVE: To investigate the genetic level causal association among hyperthyroidism, hypothyroidism, and rheumatoid arthritis (RA). METHODS: We utilized the genome-wide association studies (GWAS) summary data for exposure (hyperthyroidism and hypothyroidism) and outcome (RA) from the IEU OpenGWAS database. We used two different sets of data (test cohort and validation cohort) for causal assessment of exposure and outcome. To establish a causal relationship between these conditions, we conducted a two-sample Mendelian randomization (MR) analysis. Subsequently, we evaluated the MR analysis results for heterogeneity, horizontal pleiotropy, and outliers, aiming to assess the validity and reliability of the findings. Moreover, we conducted additional analyses to examine the robustness of the MR results, including a "Leave one out" analysis and the MR robust adjusted profile score (MR-RAPS) method, ensuring the robustness and adherence to normal distribution assumptions. RESULTS: The findings from the test cohort indicated that hyperthyroidism did not exhibit a genetic causal association with RA (P = 0.702, odds ratio [OR] 95% confidence interval [CI] = 1.021 [0.918-1.135]). Conversely, hypothyroidism displayed a positive genetic causal relationship with RA (P < 0.001, OR 95% CI = 1.239 [1.140-1.347]). The analysis results of the validation cohort are consistent with those of the test cohort. Notably, our MR analysis results demonstrated no evidence of heterogeneity, horizontal pleiotropy, or outliers. Furthermore, our MR analysis results remained unaffected by any single nucleotide polymorphism (SNP) and exhibited a normal distribution. CONCLUSION: The results of this study showed that hypothyroidism was positively correlated with RA, while hyperthyroidism was not causally correlated with RA. Hypothyroidism may as a risk factor of RA should be paid attention to in clinical work. Future studies are needed to further confirm this finding.

Analysis of the molecular mechanisms regulating how ZmEREB24 improves drought tolerance in maize (Zea mays) seedlings.

Drought stress is one of the most limiting factors of maize productivity and can lead to a sharp reduction in the total biomass when it occurs at the seedling stage. Improving drought tolerance at the seedling stage is of great importance for maize breeding. The AP2/ERF transcription factor family plays a critical role in plant response to abiotic stresses. Here, we used a preliminary previously-generated ranscriptomic dataset to identify a highly drought-stress-responsive AP2 gene, i.e., ZmEREB24. Compared to the wild type, the overexpression of ZmEREB24 in maize significantly promotes drought tolerance of transgenic plants at the seedling stage. CRISPR/Cas9-based ZmEREB24-knockout mutants showed a drought-sensitive phenotype. RNA-seq analysis and EMSA assay revealed AATGG.CT and GTG.T.GCC motifs as the main binding sites of ZmEREB24 to the promoters of downstream target genes. DAP-seq identified four novel target genes involved in proline and sugar metabolism and hormone signal transduction of ZmEREB24. Our data indicate that ZmEREB24 plays important biological functions in regulating drought tolerance by binding to the promoters of drought stress genes and modulating their expression. The results further suggest a role of ZmEREB24 in regulating drought adaptation in maize, indicating its potential importance for employing molecular breeding in the development of high-yield drought-tolerant maize cultivars.

Polymorphisms in the tumor necrosis factor gene and susceptibility to Behcet's disease: an updated meta-analysis.

PURPOSE: Studies investigating the association between the tumor necrosis factor (TNF) gene polymorphisms and Behcet's disease (BD) report conflicting results. The aim of this meta-analysis was to assess the association between TNF gene polymorphisms and BD. METHODS: A systematic literature search was conducted to identify all relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the association. RESULTS: A total of 16 articles, involving 1,708 patients with BD and 1,910 healthy controls, were included in the meta-analysis. Overall, a significant association was found between BD and the TNF -308A/G polymorphism (OR = 0.730, 95% CI = 0.608-0.877, p = 0.001). Meta-analysis of TNF -238A/G showed significant association with BD (OR = 1.512, 95% CI = 1.155-1.979, p = 0.003). The TNF -1031C allele showed significant association with BD (OR = 1.549, 95% CI = 1.190-2.015, p = 0.001). Similarly, the meta-analysis showed a significant association of the TNF -857T/C polymorphism with BD (OR = 0.758, 95% CI = 0.593-0.968, p = 0.027). Stratification by ethnicity revealed that the -308A/G and -857T/C polymorphisms were associated with BD in the Asian group, while the -238A/G and -1031C/T polymorphisms were associated with BD in the Caucasian population. CONCLUSIONS: The results of our meta-analysis suggest that TNF (-308A/G, -238A/G, -1031C/T, and -857T/C) polymorphisms are associated with susceptibility to BD.

Orthopedic Robot-Assisted Femoral Neck System in the Treatment of Femoral Neck Fracture.

Cannulated screw fixation is the main therapy for femoral neck fractures, especially in young patients. The traditional surgical procedure uses C-arm fluoroscopy to place the screw freehand and requires several guide wire adjustments, which increases the operation time and radiation exposure. Repeated drilling can also cause damage to the blood supply and bone quality of the femoral neck, which can be followed by complications such as screw loosening, nonunion, and femoral head necrosis. In order to make fixation more precise and reduce the incidence of complications, our team applied robot-assisted orthopedic surgery for screw placement using the femoral neck system to modify the traditional procedure. This protocol introduces how to import a patient's X-ray information into the system, how to perform screw path planning in software, and how the robotic arm assists in screw placement. Using this method, the surgeons can place the screw successfully the first time, improve the accuracy of the procedure, and avoid radiation exposure. The whole protocol includes the diagnosis of femoral neck fracture; the collection of intraoperative X-ray images; screw path planning in the software; precise placement of the screw under the assistance of the robotic arm by the surgeon; and verification of the implant placement.

Screening crucial lncRNAs and genes in osteoarthritis by integrated analysis.

BACKGROUND: Osteoarthritis (OA) is one of the most frequent chronic diseases with high morbidity worldwide, marked by degradation of the cartilage and bone, joint instability, stiffness, joint space stenosis and subchondral sclerosis. Due to the elusive mechanism of osteoarthritis (OA), we aimed to identify potential markers for OA and explore the molecular mechanisms underlying OA. METHODS: Expression profiles data of OA were collected from the Gene Expression Omnibus database to identify differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) in OA. Functional annotation and protein-protein interaction (PPI) networks were performed. Then, nearby DEmRNAs of DElncRNAs was obtained. Moreover, GO and KEGG pathway enrichment analysis of nearby DEmRNAs of DElncRNAs was performed. Finally, expression validation of selected mRNAs and lncRNAs was performed by quantitative reverse transcriptase-polymerase chain reaction. RESULTS: In total, 2080 DEmRNAs and 664 DElncRNAs were determined in OA. PI3K-Akt signaling pathway, Endocytosis and Rap1 signaling pathway were significantly enriched KEGG pathways in OA. YWHAB, HSPA8, NEDD4L and SH3KBP1 were four hub proteins in PPI network. The AC093484.4/TRPV2 interact pair may be involved in the occurrence and development of OA. CONCLUSION: Our study identified several DEmRNAs and DElncRNAs associated with OA. The molecular characters could provide more information for further study on OA.