Structural, elastic, mechanical, electronic, and optical properties of cubic K2Pb2O3 from first-principle study.

CONTEXT: Based on first principles, the structure, elasticity, mechanics, electronics, and optical properties of cubic K2Pb2O3 were studied. The structural parameters calculated by this method are close to the previous theoretical results. The elastic constant, bulk modulus, shear modulus, Young's modulus, Poisson's ratio, and mechanical stability are studied, and it is shown that cubic K2Pb2O3 is mechanically stable, isotropic, and brittleness. The electrical conductivity and chemical bonding of cubic K2Pb2O3 were analyzed based on the calculated band structure, density of states (DOS), and bond populations. The dispersion of optical functions, including the dielectric function, refractive index, extinction coefficient, reflectivity, absorption coefficient, and loss function, is displayed and analyzed. METHODS: All computations have been carried out based on density functional theory (DFT) as implemented in the CASTEP code. The norm conservation pseudopotential method is used to exchange correlation functionals within the generalized gradient approximation (GGA).

Design, synthesis, and biological application of A-D-A-type boranil fluorescent dyes.

For the first time, three acceptor-donor-acceptor (A-D-A)-type boranil fluorescent dyes, CSU-BF-R (R = H, CH3, and OCH3), featuring phenothiazine as the donor, were designed and synthesized. CSU-BF-R exhibited remarkable photophysical characteristics, including large Stokes shifts (>150 nm), high fluorescence quantum yields (up to 40%), long-wavelength emissions, and strong red solid-state fluorescence. Moreover, these CSU-BF-R fluorescent dyes were demonstrated to function as highly selective and sensitive ratiometric fluorescent probes for detecting hypochlorous acid (HClO). The preliminary biological applications of CSU-BF-OCH3 for sensing intracellular HClO in living cells and zebrafish were demonstrated. Therefore, CSU-BF-R possess the potential to further explore the physiological and pathological functions associated with HClO and provide valuable insights into the design of high-performance A-D-A-type fluorescent dyes.

Bone morphogenetic protein-6 suppresses TGF-ß2-induced epithelial-mesenchymal transition in retinal pigment epithelium.

AIM: To evaluate the effect of bone morphogenetic protein-6 (BMP-6) on transforming growth factor (TGF)-ß2-induced epithelial-mesenchymal transition (EMT) in retinal pigment epithelium (RPE). METHODS: Adult retinal pigment epithelial cell line (ARPE-19) were randomly divided into control, TGF-ß2 (5 µg/L), and BMP-6 small interfering RNA (siRNA) group. The cell morphology was observed by microscopy, and the cell migration ability were detected by Transwell chamber. The EMT-related indexes and BMP-6 protein levels were detected by Western blotting. Furthermore, a BMP-6 overexpression plasmid was constructed and RPE cells were divided into the control group, TGF-ß2+empty plasmid group, BMP-6 overexpression group, and TGF-ß2+BMP-6 overexpression group. The EMT-related indexes and extracellular regulated protein kinases (ERK) protein levels were detected. RESULTS: Compared with the control group, the migration of RPE cells in the TGF-ß2 group was significantly enhanced. TGF-ß2 increased the protein expression levels of α-smooth muscle actin (α-SMA), fibronectin and vimentin but significantly decreased the protein levels of E-cadherin and BMP-6 (P<0.05) in RPE. Similarly, the migration of RPE cells in the BMP-6 siRNA group was also significantly enhanced. BMP-6 siRNA increased the protein expression levels of α-SMA, fibronectin and vimentin but significantly decreased the protein expression levels of E-cadherin (P<0.05). Overexpression of BMP-6 inhibited the migration of RPE cells induced by TGF-ß2 and prevented TGF-ß2 from affecting EMT-related biomarkers (P<0.05). CONCLUSION: BMP-6 prevents the EMT in RPE cells induced by TGF-ß2, which may provide a theoretical basis for the prevention and treatment of proliferative vitreoretinopathy.

Exploring the effect of disc displacement on the risk and severity of condylar erosion in adult temporomandibular disorder patients: A CBCT and MRI study.

OBJECTIVE: The objective of the study was to investigate the relationship between types of disc displacement (DD) diagnosed by magnetic resonance imaging (MRI), and the risk (presence or absence) and severity of condylar erosion (CE) graded using cone-beam computed tomography (CBCT) in adult Temporomandibular disorders (TMD) patients. METHODS: A total of 353 TMD patients (283 females, 70 males) underwent MRI scans to categorise DD as normal (NA), anterior displacement with reduction (ADDR), or anterior displacement without reduction (ADDNR). CE severity was graded on a scale of 0-3 (absence, mild, moderate or severe) using CBCT. To establish the plausibility and cut-off points for CE diagnosis, the severity of CE was then further divided into three classifications: Grade 0 versus 1 + 2 + 3; Grades 0 + 1 versus 2 + 3; Grades 0 + 1 + 2 versus 3. Logistic regression analysis was performed, adjusting for age, gender and joint correlation. RESULTS: ADDNR significantly increased the risk of CE compared with NA (OR = 10.04, 95% CI: [6.41, 15.73]) and showed a significant increase in CE severity across all classifications (ORs = 10.04-18.95). The effects of ADDNR were significant in both genders (p < .001) and had a greater impact in females. ADDR was predominantly associated with mild CE. CONCLUSIONS: ADDNR significantly increased the risk and severity of CE independent of gender when compared to NA, whereas ADDR was mainly associated with mild CE. Slight cortical discontinuity may represent a subclinical diagnosis requiring further investigation.

Characteristics of dissolved organic matter during the cyanobacterial degradation in Chaohu Lake, China.

The actual DOM in Chaohu Lake was used to feed cyanobacterial to explore the changes of microbial communities, fluorescence spectral characteristics and molecular composition of DOM during the degradation of cyanobacteria. It is found that cyanobacterial grow periodically depending on the concentration of nutrients with the decreasing concentration of nutrient salts. Both Bacteroidetes and Actinobacteria have strong correlation with algae growth. Bacteroidetes has a positive correlation with algae growth, relationship on the contrary, Actinobacteria has a negative relationship. The humus-like components in the four groups are similar, but the protein-like component (C3) shows periodic changes with the life process of cyanobacteria. The average molecular weight of each sample detected by Orbitrap high-resolution mass spectrometer increases slightly and the DOM increase aromaticity in the end. In this study, the molecule of Carboxyl-Rich Alicyclic Molecules (CRAM) is difficult to be done by photodegradation and biodegradation in the early periods, but some molecules of CRAM are selectively degraded by microorganisms in the final period. The growth of cyanobacterial lead to increasing the concentration of protein-like and carbohydrate-like molecule of DOM in the water. In the final stage, the molecule group of CHO disappear significantly and the molecule group of heteroatomic group increase.

Temporomandibular disorder patients with excessive daytime sleepiness present greater pain intensity and reduced jaw function.

BACKGROUND: Sleep disorders are associated with temporomandibular disorders (TMDs). Limited studies have focused on excessive daytime sleepiness (EDS) and its impact on jaw functions in TMD patients. OBJECTIVE: The aim of the present investigation was to identify the impact of EDS on pain and jaw function in TMD patients. METHODS: A total of 338 TMD patients (50 males and 288 females) was included. The Epworth Sleepiness Scale (ESS) was used to classify patients into EDS group (score ≥ 10) and non-EDS group (score < 10). The Jaw Functional Limitation Scale 8-item (JFLS-8) was used to assess the severity of jaw dysfunction. Pain intensity was evaluated using the Visual Analogue Scale (VAS). Anxiety and depression were evaluated using the Generalised Anxiety Disorder 7-item (GAD-7) and the Patient Health Questionnaire 9-item (PHQ-9). All included patients were diagnosed with pain-related TMD (PT), intra-articular TMD (IT) or combined TMD (CT). RESULTS: Compared with non-EDS patients, EDS patients exhibited more severe jaw dysfunction, greater pain intensity and higher PHQ-9 scores (p < .05). Multivariate analyses showed that EDS (B = 3.69), female gender (B = 3.69), and elevated GAD-7 score (B = 0.73) were significantly associated with an increased score on the JFLS-8 (p < .05). Moreover, bivariate logistic regression analysis indicated a significant relationship between EDS and PT (OR = 2.70, p = .007). CONCLUSION: The presence of EDS was more closely related to PT, but the causal relationship between them needs to be further confirmed. More concern and intervention to alleviate poor sleep quality might be highlighted during the treatment of TMD, especially PT subtype.

Intrinsic Wave Velocity Propagation: A Novel Parameter for Assessing the Effect of Anthracycline Chemotherapy Agents on Cardiac Diastolic Function in Breast Cancer Patients.

OBJECTIVE: Anthracycline chemotherapeutic agents have significant cardiotoxicity. The present study emphasized the effect of anthracycline chemotherapy drugs on left ventricular (LV) myocardial stiffness in breast cancer patients by measuring the intrinsic wave velocity propagation (IVP), and evaluating the potential clinical value of IVP in detecting early LV diastolic function impairment. METHODS: A total of 68 newly diagnosed breast cancer patients, who were treated with anthracycline-based chemotherapy, were analyzed. Transthoracic echocardiography was performed at baseline (T0), and after 1, 2, 3, 4 and 8 chemotherapeutic cycles (T1, T2, T3, T4 and T5, respectively). Then, the IVP, LV strain parameters [global longitudinal strain (GLS), longitudinal peak strain rate at systole (LSRs), longitudinal peak strain rate at early diastole (LSRe), longitudinal peak strain rate at late diastole (LSRa), and the E/LSRe ratio], and conventional echocardiographic parameters were obtained and further analyzed. A relative reduction of >15% in GLS was considered a marker of early LV subclinical dysfunction. RESULTS: Compared to the T0 stage, IVP significantly increased at the T1 stage. However, there were no significant changes in GLS, LSRs, or LSRe between the T0 and T1 stages. These parameters significantly decreased from the T2 stage. LSRa started to significantly decrease at the T5 stage, and the E/LSRe ratio started to significantly increase at the T3 stage (all P<0.05). At the T0 stage, IVP (AUC=0.752, P<0.001) had a good predictive value for LV subclinical dysfunction after chemotherapy. CONCLUSIONS: IVP is a potentially sensitive parameter for the early clinical assessment of anthracycline-related cardiac diastolic impairment.

A Clinical Analysis of Prognosis and Patient-Reported Outcomes of Oncoplastic Breast-Conserving Surgery for Early Breast Cancer: A Retrospective Cohort Study.

PURPOSE: Approximately 25-30% of patients suffer from breast deformity and/or asymmetry after conventional breast-conserving surgery (CBCS). Generally, it is thought that oncoplastic breast-conserving surgery (OBCS) results in an improved cosmetic result; however, studies comparing the prognosis and aesthetic outcomes of CBCS and OBCS in early breast cancer (EBC) are inadequate. METHODS: A total of 143 patients were included in this retrospective cohort study; 53 underwent OBCS and 90 underwent CBCS. The resected weight, complications, esthetic results, patient satisfaction, and recurrence rate were compared between the groups. Patient-reported outcomes (PRO) were assessed by the BREAST-Q questionnaire. RESULTS: The mean age of the patients in OBCS group was 43.8 years. This was younger than that in CBCS group (49.1 years, p < 0.001). Postoperative complications (11.3% vs. 8.9%, p = 0.64) and re-excision (5.7% vs. 6.7%, p > 0.99) rates were similar. The OBCS group had higher breast satisfaction and psychosocial well-being than the CBCS group (75 vs. 63, p < 0.001 and 84 vs. 77, p = 0.05); however, sexual well-being (56 vs. 66, p = 0.05) and physical well-being (65 vs. 76, p < 0.001) were worse in OBCS. After 42.3 (range: 12.6-69.2)-month median follow-up, no difference in event-free survival (EFS) was demonstrated between the groups (p = 0.13). CONCLUSION: Although OBCS has the better aesthetic outcomes and identical oncological safety in comparison with CBCS, the sexual and physical well-being in OBCS are not improved for Asian patients. Hence, choosing an appropriate procedure may be more important for the typically small to moderate-sized breasts characteristic of Asian females unlike Westerners. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Inhibition of 6-Phosphogluconate Dehydrogenase Reverses Epirubicin Resistance Through Metabolic Reprograming in Triple-Negative Breast Cancer Cells.

At present, chemotherapy is the most effective strategy for treating triple-negative breast cancer (TNBC), but its efficacy was limited by the development of chemo-resistance. The exact mechanism of chemoresistance still remains unclear. This study aims to examine whether 6-phosphogluconate dehydrogenase (6PGD), a key enzyme in the oxidative pentose phosphate pathway (PPP), could promote the resistance of TNBC cells to epirubicin. A TNBC epirubicin-resistant cell line was developed by increasing concentration and the effectiveness was tested. The expression and knockdown efficiency of 6PGD were further validated by performing quantitative real-time PCR (qPCR) and Western blot. The effects of 6PGD on parental and drug-resistant TNBC cell lines were verified based on proliferation and apoptosis experiments. Finally, nicotinamide adenine dinucleotide phosphate (NADPH) and lactate quantitative experiments were performed to examine the mechanism of 6PGD in promoting drug resistance. Epirubicin-resistant cancer cells exhibited a higher level of 6PGD in contrast to epirubicin-sensitive cells. In addition, 6PGD inhibited by genetic and pharmacological approaches significantly suppressed the growth and survival of both epirubicin-sensitive and epirubicin-resisteant TNBC cells. It should be noted that 6PGD inhibition sensitized epirubicin-resistant TNBC cells to epirubicin treatment. Moreover, it was also found that the levels of NADPH and lactate increased in epirubicin-resistant TNBC cells but decreased in response to 6PGD inhibition. The present results indicated that 6PGD inhibition disrupted metabolic reprogramming in epirubicin-resistant TNBC cells. Our work demonstrated that 6PGD inhibition reversed the resistance of TNBC cells to epirubicin, providing an alternative therapeutic choice to tackle the challenge of epirubicin resistance in TNBC treatment.

Exploring the prospect of intrinsic wave propagation in evaluating myocardial stiffness among patients with type 2 diabetes.

Background: Diabetes predisposes affected individuals to impaired myocardial perfusion and ischemia, leading to cardiac dysfunction. Increased myocardial stiffness is an independent and significant risk factor in diastolic dysfunction. This study sought to estimate myocardial stiffness in Type 2 diabetes (T2DM) patients using the intrinsic wave velocity propagation (IVP) along the longitudinal wall motion during late diastole and evaluate the value of IVP in assessing cardiac function and structure. Methods: 87 and 53 participants with and without T2DM (control group) were enrolled. Of the 87 T2DM patients (DM group), 43 were complicated with hypertension (DM + H group), and 44 were not (DM-H group). Ultrasound parameters were measured and analyzed, including color M-mode flow propagation velocity, global longitudinal systolic strain (GLS), and IVP. Results: IVP was higher in the DM group than in the control group (1.62 ± 0.25 m/s and 1.40 ± 0.19 m/s, P < 0.001). After stratification for hypertension, IVP in both DM + H (1.71 ± 0.25 m/s) and DM-H (1.53 ± 0.20 m/s) groups were found to be significantly higher than that in the control group (1.40 ± 0.19 m/s); also, the difference of IVP between DM + H and DM-H group reached statistical significance. Moreover, IVP was significantly correlated with flow propagation velocity during early diastole (Pve) (r = -0.580, P < 0.001), flow propagation velocity during late diastole (Pva) (r = 0.271, P < 0.001), GLS (r = 0.330, P < 0.001), interventricular septal thickness at end-diastole (IVSd) (r = 0.321, P < 0.001), blood glucose (r = 0.246, P < 0.003), systolic blood pressure (r = 0.370, P < 0.001) and diastolic blood pressure (r = 0.389, P < 0.001). Conclusions: The results indicated the application potential of IVP in assessing the early detection of cardiac function changes noninvasively and sensitively. The correlation with myocardial stiffness warrants further studies to substantiate its potential clinical utility.

Multivariate analysis compares and evaluates drought and flooding tolerances of maize germplasm.

Drought and flooding are the two most important environmental factors limiting maize (Zea mays L.) production globally. This study aimed to investigate the physiological mechanisms and accurate evaluation indicators and methods of maize germplasm involved in drought and flooding stresses. The twice replicated pot experiments with 60 varieties, combined with the field validation experiment with 3 varieties, were conducted under well-watered, drought, and flooding conditions. Most varieties exhibited stronger tolerance to drought than flooding due to higher antioxidant enzyme activities, osmotic adjustment substances, and lower reactive oxygen species. In contrast, flooding stress resulted in higher levels of reactive oxygen species (particularly O2-), ascorbate peroxidase, catalase, peroxidase, and soluble sugars but lower levels of superoxide dismutase, proline, and soluble protein compared with well-watered conditions. Superoxide dismutase, peroxidase, catalase, ascorbate peroxidase, proline, soluble sugars, and protein contents, in addition to plant height, leaf area/plant, and stem diameter, were accurate and representative indicators for evaluating maize tolerance to drought and flooding stresses and could determine a relatively high mean forecast accuracy of 100.0% for the comprehensive evaluation value. A total of 4 principal components were extracted, in which different principal components played a vital role in resisting different water stresses. Finally, the accuracy of the 3 varieties screened by multivariate analysis was verified in the field. This study provides insights into the different physiological mechanisms and accurate evaluation methods of maize germplasm involved in drought and flooding stresses, which could be valuable for further research and breeding.

Loss of function of SSIIIa and SSIIIb coordinately confers high RS content in cooked rice.

The sedentary lifestyle and refined food consumption significantly lead to obesity, type 2 diabetes, and related complications, which have become one of the major threats to global health. This incidence could be potentially reduced by daily foods rich in resistant starch (RS). However, it remains a challenge to breed high-RS rice varieties. Here, we reported a high-RS mutant rs4 with an RS content of ~10.8% in cooked rice. The genetic study revealed that the loss-of-function SSIIIb and SSIIIa together with a strong Wx allele in the background collaboratively contributed to the high-RS phenotype of the rs4 mutant. The increased RS contents in ssIIIa and ssIIIa ssIIIb mutants were associated with the increased amylose and lipid contents. SSIIIb and SSIIIa proteins were functionally redundant, whereas SSIIIb mainly functioned in leaves and SSIIIa largely in endosperm owing to their divergent tissue-specific expression patterns. Furthermore, we found that SSIII experienced duplication in different cereals, of which one SSIII paralog was mainly expressed in leaves and another in the endosperm. SSII but not SSIV showed a similar evolutionary pattern to SSIII. The copies of endosperm-expressed SSIII and SSII were associated with high total starch contents and low RS levels in the seeds of tested cereals, compared with low starch contents and high RS levels in tested dicots. These results provided critical genetic resources for breeding high-RS rice cultivars, and the evolutionary features of these genes may facilitate to generate high-RS varieties in different cereals.

Do Temporomandibular Disorder Patients with Joint Pain Exhibit Forward Head Posture? A Cephalometric Study.

Purpose: To evaluate head and cervical posture in individuals with or without temporomandibular disorders (TMDs) and to assess the correlations between pain, severity of symptoms, and posture. Methods: A total of 384 patients (129 males and 255 females) was included. The Fonseca Anamnestic Index (FAI) was used to assess the severity and prevalence of TMD and the presence of temporomandibular joint (TMJ) pain. Patients were divided into three groups: the TMD-free group, TMD without TMJ pain group, and TMD with TMJ pain group. Subsequently, the patients with TMJ pain were further divided into mild TMD and moderate/severe TMD groups. Nine parameters were traced on cephalograms to characterize the head and cervical posture. Results: TMD patients with TMJ pain showed increased forward head posture (FHP) than patients without TMJ pain and TMD-free subjects. No significant difference was observed between the TMD patients without TMJ pain and TMD-free subjects. In the TMD patients with the TMJ pain group, the moderate/severe TMD patients demonstrated increased FHP compared to mild TMD patients. TMD patients with joint pain had greater CVT/RL (B = 3.099), OPT/RL (B = 2.117), and NSL/C2' (B = 4.646) than the patients without joint pain after adjusting for confounding variables (P < 0.05). Conclusion: TMD patients with TMJ pain showed increased FHP compared to other groups, and FHP became more significant as TMD severity increased in male patients, indicating the FHP might play an important role in the development of TMJ pain. In the clinical assessment of TMD, the patients' abnormal head and cervical posture might be considered.

Quantitative Assessment of Right Ventricular Function in Patients With Systemic Lupus Erythematosus Using the Novel Non-invasive Pressure-Strain Loop.

OBJECTIVE: Current echocardiography evaluation of right ventricular (RV) function, which heralds the prognosis in patients with systemic lupus erythematosus (SLE), is of limited utility. The non-invasive pressure-strain loop (PSL), an emerging technique, has been found to feasible, sensitive and accurate in the diagnosis of cardiovascular diseases. The aim of this study was to quantitatively evaluate, using the non-invasive PSL, the right ventricular myocardial work (RVMW) in SLE patients. METHODS: Seventy-five SLE patients were recruited and grouped by pulmonary artery systolic pressure (PASP) into normal (group A, N = 26), mild (group B, N = 22) and moderate to severe (group C, N = 27) groups. Twenty-five healthy volunteers undergoing physical examination were recruited as the control group. Right ventricular global myocardial work index (RVGWI), global constructive work (RVGCW), global wasted work (RVGWW), global work efficiency (RVGWE), global longitudinal strain (RVGLS) and other conventional parameters were measured. DISCUSSION: There were no differences between group A and the control group with respect to RVLS, RVGLS and all RVMW parameters (all p values > 0.05). RVGWI and RVGCW significantly differed among the other groups (all p values < 0.05). RVGWE was significantly lower and RVGWW was significantly higher in group C than in the control group and groups A and B (all p values < 0.05). Compared with the control group, RVGWW was significantly increased and RVGLS was significantly decreased in group B (all p values < 0.05). All but one RVMW parameter moderately to strongly correlated with SLE disease activity index (SLEDAI) and World Health Organization Functional Class (WHO-FC). RVGWW (area under the receiver operating characteristic curve [AUC] = 0.893) and RVGWE (AUC = 0.877) were sensitive parameters in detecting earlier cardiac dysfunction in SLE patients. CONCLUSION: RVGWW and RVGWE serve as sensitive and promising parameters in the integrative analysis of early right ventricular dysfunction in SLE patients. To conclude, non-invasive PSL, the novel method, facilitates the quantitative assessment of RVMW in SLE patients.

Fuzheng Xiaoai Decoction 1 ameliorated cancer cachexia-induced muscle atrophy via Akt-mTOR pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Fuzheng Xiaoai Decoction 1 (FZXAD1) is a clinical experience prescription for the treatment of cancer patients at an advanced stage. FZXAD1 has been used for more than 10 years in the clinic and can effectively improve the deficiency syndrome of cancer patients. However, its mechanisms need further clarification. AIM OF THE STUDY: To check the effects of FZXAD1 in colon 26 (C26) cancer cachexia mice and try to clarify the mechanisms of FZXAD1 in ameliorating cancer cachexia symptoms. MATERIALS AND METHODS: An animal model of cancer cachexia was constructed with male BALB/c mice bearing C26 tumor cells. Food intake, body weight and tumor size were measured daily during the animal experiment. Tissue samples in different groups including tumor and gastrocnemius muscle, were dissected and weighed at the end of the assay. Serum biochemical indicators such as total protein (TP), glucose (GLU) and alkaline phosphatase (ALP) were also detected. Network pharmacology-based analysis predicted the possible targets and signaling pathways involved in the effects of FZXAD1 on cancer cachexia therapy. Western blotting assays of the gastrocnemius muscle tissues from C26 tumor-bearing mice were then used to confirm the predicted possible targets of FZXAD1. RESULTS: The results of animal experiments showed that FZXAD1 could ameliorate cancer cachexia by alleviating the muscle wasting as well as kidney atrophy and increasing the body weight of cancer cachexia mice. AKT1, MTOR, MAPK3, HIF1A and MAPK1 were predicted as the core targets of FZXAD1. Western blotting confirmed the prediction that FZXAD1 increased the expression levels of phosphorylated Akt and mTOR in the muscle tissues. In addition, FZXAD1 treatment obviously ameliorated the increased levels of HIF-1α and phosphorylated Erk1/2 in C26 tumor-bearing mice. CONCLUSION: FZXAD1 effectively ameliorated cancer cachexia in an animal model of mice, which is consistent with its efficacy in the treatment of cancer patients. The mechanisms of FZXAD1 might be mainly based on its alleviating effects on muscle atrophy by activating the Akt-mTOR pathway and thus helping to maintain body weight.

The OTUD1-Notch2-ICD axis orchestrates allogeneic T cell-mediated graft-versus-host disease.

Disorders of the ubiquitin-proteasome system (UPS) are known to influence the incidence and mortality of various diseases. It remains largely unknown whether and how the UPS affects the onset and progression of acute graft-verus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study demonstrated that the deubiquitinase OTUD1 is an essential regulator of aGVHD. Activation of CD4+ T cells after allo-HSCT, elevated the protein levels of OTUD1, which in turn interacted with the Notch2-ICD (NICD) to cleave the ubiquitin of NICD at the K1770 site, thereby inducing NICD protein accumulations in T cells. OTUD1-driven NICD signaling promoted the differentiation and functions of Th1 and Th17 cells and amplified the cascade of aGVHD. Moreover, by screening a FDA-approved drugs library the study identified dapagliflozin as an inhibitor targeting the OTUD1/NICD axis. Dapagliflozin administration significantly prolonged the survival of aGVHD mice. This study characterized a previously unknown role of OTUD1 in T cell-mediated allogeneic responses and provided a promising therapeutic strategy to target OTUD1 for the alleviation of aGVHD.

Risk estimation of degenerative joint disease in temporomandibular disorder patients with different types of sagittal and coronal disc displacements: MRI and CBCT analysis.

BACKGROUND: Degenerative joint disease (DJD) can be associated with disc displacement (DD) in temporomandibular disorder (TMD) patients. However, the relationship between different types of DDs and DJD remains unclear. OBJECTIVES: To investigate the odds ratios of different types of sagittal and coronal DDs confirmed by magnetic resonance imaging (MRI) and DJD confirmed by cone-beam computed tomography (CBCT) in TMD patients. METHODS: Radiographic data from 69 males and 232 females were collected for analysis. CBCT was used to diagnose DJD, with criteria including erosion, osteophytes, generalised sclerosis and cysts in the joint. Eight types of DDs were evaluated by sagittal and coronal MRIs: NA, no abnormality; SW, sideways; ADDR, anterior with reduction; ADDR+SW; ADDNR, anterior without reduction; ADDNR + SW; single SW; PDD, posterior; PDD + SW. The odds ratios of DJD in joints with different types of DDs were determined after joint correlation, age and gender adjustment. RESULTS: Compared with NA, the odds ratio of DJD in ADDR was 2.397 (95% CI [confidence interval]: 1.070-5.368), ADDR + SW was 4.808 (95% CI: 1.709-3.528), ADDNR was 29.982 (95% CI: 15.512-57.950) and ADDNR + SW was 25.974 (95% CI: 12.743-52.945). Erosion was significantly increased in ADDR, ADDR + SW, ADDNR and ADDNR + SW; osteophytes were significantly increased in ADDR + SW, ADDNR and ADDNR + SW; and generalised sclerosis and cysts were significantly increased in ADDNR and ADDNR + SW. There were no significant associations between single SW, PDD, PDD + SW and the DJD. CONCLUSIONS: ADDR, ADDR+SW, ADDNR and ADDNR+SW were associated with DJD. ADDNR had a significantly higher prevalence of DJD than ADDR. There were no significant relationships between single SW, PDD, PDD + SW and the DJD.

Do Specific Craniomaxillofacial Features Correlate with Psychological Distress in Adult Pretreatment Orthodontic Patients? A Cephalometric Study.

Purpose: To explore the relationship between craniomaxillofacial features and psychological distress among adult pretreatment orthodontic patients. Methods: A group of 190 patients (95 males and 95 females) was included. Questionnaires including the Kessler psychological distress scale (K10) were sent to patients, and cephalograms were collected. Patients were divided into two groups according to K10 score: psychological distress group (score ≥ 20) and no psychological distress group (score < 20). Nineteen hard tissue and thirteen soft tissue parameters were traced on cephalograms to characterize the craniomaxillofacial features. Results: There was no significant difference in gender or age distribution between the two groups. Male patients with psychological distress showed statistically significantly larger anterior facial height (AFH) (126.62 mm vs. 120.97 mm), upper lip length (25.11 mm vs. 23.26 mm), and smaller overbite (1.21 mm vs. 2.75 mm) than patients without psychological distress. Male patients with hyperdivergent pattern and open bite were more likely to have psychological distress. None of the parameters showed statistical differences across groups in females. Frankfort-mandibular plane angle (r = 0.235), Bjork's sum (r = 0.311), AFH (r = 0.322), overbite (r = -0.238), AFH/posterior facial height (r = 0.251), and upper anterior facial height (UAFH)/lower anterior facial height (LAFH) (r = -0.230) were correlated with K10 score in males. After adjusting gender and age, the AFH (B = 0.147) and UAFH/LAFH (B = -14.923) were significantly related with the K10 score. Conclusion: Psychological distress was mainly correlated with hyperdivergent pattern, open bite, and larger lower anterior facial height proportion in pretreatment orthodontic patients. Orthodontists should be aware of the possible underlying psychological distress in patients with specific craniomaxillofacial features. Clinical assessment of psychological distress may need to take into account gender differences in patients.

Targeting a gene regulatory element enhances rice grain yield by decoupling panicle number and size.

Crop genetic improvement requires balancing complex tradeoffs caused by gene pleiotropy and linkage drags, as exemplified by IPA1 (Ideal Plant Architecture 1), a typical pleiotropic gene in rice that increases grains per panicle but reduces tillers. In this study, we identified a 54-base pair cis-regulatory region in IPA1 via a tiling-deletion-based CRISPR-Cas9 screen that, when deleted, resolves the tradeoff between grains per panicle and tiller number, leading to substantially enhanced grain yield per plant. Mechanistic studies revealed that the deleted fragment is a target site for the transcription factor An-1 to repress IPA1 expression in panicles and roots. Targeting gene regulatory regions should help dissect tradeoff effects and provide a rich source of targets for breeding complementary beneficial traits.

Application of Protoplast Regeneration to CRISPR/Cas9 Mutagenesis in Nicotiana tabacum.

Protoplast transfection is widely used in plant research to rapidly evaluate RNA degradation, reporter assay, gene expression, subcellular localization, and protein-protein interactions. In order to successfully use protoplast transfection with the newly emerging clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) protein editing platform, high yield of protoplasts, stable transfection efficiency, and reliable regeneration protocols are necessary. The Nicotiana tabacum transient protoplast transfection and regeneration system can effectively obtain target gene mutations in regenerated plants without transgenes and is thus a very attractive technique for evaluating gene editing reagents using CRISPR/Cas-based systems. Here, we describe in detail sterilized seed germination, culture conditions, isolation of Nicotiana tabacum protoplasts from tissue culture explants, construction of a vector containing the Cas protein and sgRNA cassette, highly efficient polyethylene glycol-calcium transient transfection of plasmids delivered into protoplasts, evaluation of mutagenesis efficiency and genotype analysis from protoplasts and regenerated plants, and the regeneration conditions to obtain CRISPR-edited plants from single protoplasts.