MIR143HG promotes methylation of transcription factor HOXB7 promoter by recruiting methyltransferase DNMT1 to prevent the progression of colon cancer.

In recent years, accumulating evidence has demonstrated the role of long noncoding RNAs (lncRNAs) in colon cancer. We aim to investigate the role of MIR143HG, also known as CARMN (Cardiac mesoderm enhancer-associated noncoding RNA) in colon cancer and explore the related mechanisms. An RNAseq data analysis was performed to screen differentially expressed lncRNAs associated with colon cancer. Next, MIR143HG expression was quantified in colon cancer cells. Moreover, the contributory roles of MIR143HG in the progression of colon cancer with the involvement of DNMT1 and HOXB7 (Homeobox B7) were evaluated after restored MIR143HG or depleted HOXB7. Finally, the effects of MIR143HG were investigated in vivo by measuring tumor formation in nude mice. High-throughput transcriptome sequencing was employed to validate the specific mechanisms by which MIR143HG and HOXB7 affect tumor growth in vivo. MIR143HG was found to be poorly expressed, while HOXB7 was highly expressed in colon cancer. MIR143HG could promote HOXB7 methylation by recruiting DNMT1 to reduce HOXB7 expression. Upregulation of MIR143HG or downregulation of HOXB7 inhibited cell proliferation, invasion and migration and facilitated apoptosis in colon cancer cells so as to delay the progression of colon cancer. The same trend was identified in vivo. Our study provides evidence that restoration of MIR143HG suppressed the progression of colon cancer via downregulation of HOXB7 through DNMT1-mediated HOXB7 promoter methylation. Thus, MIR143HG may be a potential candidate for the treatment of colon cancer.

Transient enhancement of stimulus-evoked activity in neocortex during sensory learning.

Synaptic potentiation has been linked to learning in sensory cortex, but the connection between this potentiation and increased sensory-evoked neural activity is not clear. Here, we used longitudinal in vivo Ca2+ imaging in the barrel cortex of awake mice to test the hypothesis that increased excitatory synaptic strength during the learning of a whisker-dependent sensory-association task would be correlated with enhanced stimulus-evoked firing. To isolate stimulus-evoked responses from dynamic, task-related activity, imaging was performed outside of the training context. Although prior studies indicate that multiwhisker stimuli drive robust subthreshold activity, we observed sparse activation of L2/3 pyramidal (Pyr) neurons in both control and trained mice. Despite evidence for excitatory synaptic strengthening at thalamocortical and intracortical synapses in this brain area at the onset of learning-indeed, under our imaging conditions thalamocortical axons were robustly activated-we observed that L2/3 Pyr neurons in somatosensory (barrel) cortex displayed only modest increases in stimulus-evoked activity that were concentrated at the onset of training. Activity renormalized over longer training periods. In contrast, when stimuli and rewards were uncoupled in a pseudotraining paradigm, stimulus-evoked activity in L2/3 Pyr neurons was significantly suppressed. These findings indicate that sensory-association training but not sensory stimulation without coupled rewards may briefly enhance sensory-evoked activity, a phenomenon that might help link sensory input to behavioral outcomes at the onset of learning.

Germination responses of Lens Culiunaris L. seeds to osmotic potentials at cardinal temperatures using hydrothermal time model.

BACKGROUND: Lentil is a significant legume that are consumed as a staple food and have a significant economic impact around the world. The purpose of the present research on lentil was to assess the hydrothermal time model's capacity to explain the dynamics of Lens culinaris L. var. Markaz-09 seed germination, as well as to ascertain the germination responses at various sub-optimal temperatures (T) and water potentials (Ψ). In order to study lentil seed germination (SG) behavior at variable water potentials (Ψs) and temperatures (Ts). A lab experiment employing the hydrothermal time model was created. Seeds were germinated at six distinct temperatures: 15 0С, 20 0С, 25 0С, 30 0С, 35 0С, and 40 0С, with five Ψs of 0, -0.3, -0.6, -0.9, and - 1.2 MPa in a PEG-6000 (Polyethylene glycol 6000) solution. RESULTS: The results indicated that the agronomic parameters like Germination index (GI), Germination energy (GE), Timson germination index (TGI), were maximum in 25 0C at (-0.9 MPa) and lowest at 40 0C in 0 MPa. On other hand, mean germination time (MGT) value was highest at 15 0C in -1.2 MPa and minimum at 40 0C in (-0.6 MPa) while Mean germination rate (MGR) was maximum at 40 0C in (0 MPa) and minimum at 15 0C in (-0.6 MPa). CONCLUSIONS: The HTT model eventually defined the germination response of Lens culinaris L. var. Markaz-09 (Lentil) for all Ts and Ψs, allowing it to be employed as a predictive tool in Lens culinaris L. var. Markaz-09 (Lentil) seed germination simulation models.

Salicylic acid and Tocopherol improve wheat (Triticum aestivum L.) Physio-biochemical and agronomic features grown in deep sowing stress: a way forward towards sustainable production.

BACKGROUND: The rate of germination and other physiological characteristics of seeds that are germinating are impacted by deep sowing. Based on the results of earlier studies, conclusions were drawn that deep sowing altered the physio-biochemical and agronomic characteristics of wheat (Triticum aestivum L.). RESULTS: In this study, seeds of wheat were sown at 2 (control) and 6 cm depth and the impact of exogenously applied salicylic acid and tocopherol (Vitamin-E) on its physio-biochemical and agronomic features was assessed. As a result, seeds grown at 2 cm depth witnessed an increase in mean germination time, germination percentage, germination rate index, germination energy, and seed vigor index. In contrast, 6 cm deep sowing resulted in negatively affecting all the aforementioned agronomic characteristics. In addition, deep planting led to a rise in MDA, glutathione reductase, and antioxidants enzymes including APX, POD, and SOD concentration. Moreover, the concentration of chlorophyll a, b, carotenoids, proline, protein, sugar, hydrogen peroxide, and agronomic attributes was boosted significantly with exogenously applied salicylic acid and tocopherol under deep sowing stress. CONCLUSIONS: The results of the study showed that the depth of seed sowing has an impact on agronomic and physio-biochemical characteristics and that the negative effects of deep sowing stress can be reduced by applying salicylic acid and tocopherol to the leaves.

Research progress on the conformational properties of comb-like polymers in dilute solutions.

As a special type of branched polymers, comb-like polymers simultaneously possess the structural characteristics of a linear backbone profile and crowded sidechain branches/grafts, and such structural uniqueness leads to reduced interchain entanglement, enhanced molecular orientation, and unique stimulus-response behavior, which greatly expands the potential applications in the fields of super-soft elastomers, molecular sensors, lubricants, photonic crystals, etc. In principle, all these molecular features can be traced back to three structural parameters, i.e., the degree of polymerization of the backbone (Nb), the degree of polymerization of the graft sidechain (Ng), and the grafting density (σ). Consequently, it is of great importance to understand the correlation mechanism between the structural characteristics and physicochemical properties, among which, the conformational properties in dilute solution have received the most attention due to its central position in polymer science. In the past decades, the development of synthetic chemistry and characterization techniques has greatly stimulated the progress of this field, and a number of experiments have been executed to verify the conformational properties; however, due to the complexity of the structural parameters and the diversity of the chemical design, the achieved experimental progress displays significant controversies compared with the theoretical predictions. This review aims to provide a full picture of recent research progress on this topic, specifically, (1) first, a few classical theoretical models regarding the chain conformation are introduced, and the quasi-two-parameter (QTP) theory for the conformation analysis is highlighted; (2) second, the research progress of the static conformation of comb-like polymers in dilute solution is discussed; (3) third, the research progress of the dynamic conformation in dilute solution is further discussed. The key issues, existing controversies and future research directions are also highlighted. We hope that this review can provide insightful information for the understanding of the conformational properties of comb-like polymers, open a new door for the regulation of conformational behavior in related applications, and promote related theoretical and experimental research in the community.

Prognostic value of native T1 and extracellular volume in patients with immunoglubin light-chain amyloidosis.

BACKGROUND: Cardiac involvement in patients with immunoglubin light-chain amyloidosis (AL) is a major determinant of treatment choice and prognosis, and early identification of high-risk patients can initiate intensive treatment strategies to achieve better survival. This study aimed to investigate the prognostic value of native T1 and ECV in patients with AL-cardiac amyloidosis (CA). METHODS: A total of 38 patients (mean age 59 ± 11 years) with AL diagnosed histopathologically from July 2017 to October 2021 were collected consecutively. All patients were performed 3.0-T cardiac magnetic resonance (CMR) including cine, T1 mapping, and late gadolinium enhancement (LGE). Pre- and post-contrast T1 mapping images were transferred to a dedicated research software package (CVI42 v5.11.3) to create parametric T1 and ECV values. In addition, clinical and laboratory data of all patients were collected, and patients or their family members were regularly followed up by telephone every 3 months. The starting point of follow-up was the time of definitive pathological diagnosis, and the main endpoint was all-cause death. Kaplan-Meier analysis and Cox proportional risk model were used to evaluate the association between native T1 and ECV and death in patients with CA. RESULTS: After a median follow-up of 27 (16, 37) months, 12 patients with CA died. Kaplan-Meier analysis showed that elevated native T1 and ECV were closely associated with poor prognosis in patients with CA. The survival rate of patients with ECV > 44% and native T1 > 1389ms were significantly lower than that of patients with ECV ≤ 44% and native T1 ≤ 1389ms (Log-rank P < 0.001), and was not associated with the presence of LGE. After adjusting for clinical risk factors and CMR measurements in a stepwise multivariate Cox regression model, ECV [risk ratio (HR):1.37, 95%CI: 1.09-1.73, P = 0.008] and native T1 (HR:1.01, 95%CI: 1.00-1.02, P = 0.037) remained independent predictors of all-cause mortality in patients with CA. CONCLUSIONS: Both native T1 and ECV were independently prognostic for mortality in patients with CA, and can be used as important indicators for clinical prognosis assessment of AL.

FosGFP expression does not capture a sensory learning-related engram in superficial layers of mouse barrel cortex.

Immediate-early gene (IEG) expression has been used to identify small neural ensembles linked to a particular experience, based on the principle that a selective subset of activated neurons will encode specific memories or behavioral responses. The majority of these studies have focused on "engrams" in higher-order brain areas where more abstract or convergent sensory information is represented, such as the hippocampus, prefrontal cortex, or amygdala. In primary sensory cortex, IEG expression can label neurons that are responsive to specific sensory stimuli, but experience-dependent shaping of neural ensembles marked by IEG expression has not been demonstrated. Here, we use a fosGFP transgenic mouse to longitudinally monitor in vivo expression of the activity-dependent gene c-fos in superficial layers (L2/3) of primary somatosensory cortex (S1) during a whisker-dependent learning task. We find that sensory association training does not detectably alter fosGFP expression in L2/3 neurons. Although training broadly enhances thalamocortical synaptic strength in pyramidal neurons, we find that synapses onto fosGFP+ neurons are not selectively increased by training; rather, synaptic strengthening is concentrated in fosGFP- neurons. Taken together, these data indicate that expression of the IEG reporter fosGFP does not facilitate identification of a learning-specific engram in L2/3 in barrel cortex during whisker-dependent sensory association learning.

First Report of Powdery Mildew caused by Erysiphe astragali on Sphaerophysa salsula.

Sphaerophysa salsula (Pall.) DC., also known as Yang Liao Pao, belongs to the Leguminosae family and is the only existing species in the Sphaerophysa genus. S. salsula is tolerance to cold, high salt, and alkaline soil, it is widely cultivated in China as a forage crop, and used as a Chinese folk medicine to treat hypertension (Ma et al., 2002). In 2023, signs and symptoms similar to powdery mildew were found on S. salsula planted in Tumd left (40.515°N, 110.424°E), Baotou City, Inner Mongolia Autonomous Region, China. The white powdery substance covered 90% of the leaf area, and the infected plants showed weak growth and senescence. More than 80% of plants (n=200) had these powdery mildew-like symptoms. Hyphal appressoria are solitary, conidiophores have few branches and septa. Conidia are cylindrical to clavate, 25-32 µm long and 8-15 µm wide (n=30), conidia form single subapical germ tubes, straight to curved-sinuous, with swollen apex or distinctly lobed conidial appressorium. Based on these morphological characteristics, the fungus was tentatively identified as an Erysiphe sp. (Schmidt and Braun 2020). Fungal structures were isolated from diseased leaves, and genomic DNA of the pathogen was extracted using the method described by Zhu et al. (2022). The internal transcribed spacer (ITS) region was amplified by PCR using the primers PMITS1/PMITS2 (Cunnington et al. 2003) and the amplicon sequenced by Invitrogen (Shanghai, China). The powdery mildew strain, named as KMD (GenBank accession no.: PP267067), showed an identity of 100% (645/645bp) with Erysiphe astragali, a powdery mildew reported on Astragalus glycyphyllos in Golestan, Iran (GenBank: OP806834) and identity of 99.6% (643/645bp) with Erysiphe astragali (GenBank: MW142495), a powdery mildew reported on A. scaberrimus in Inner Mongolia, China (Sun et al. 2023). Pathogenicity tests were conducted by brushing the conidia from infected S. salsula leaves onto leaves of four healthy plants, while four control plants were brushed in the same manner. All the treated plants were placed in separate growth chambers maintained at 19°C and 65% humidity, with a 16 h light/8 h dark photoperiod. Nine days after inoculation, the treated plants showed powdery mildew symptoms, while the control plants remained asymptomatic. The same results were obtained for two repeated pathogenicity experiments. The powdery mildew fungus was reisolated and identified as E. astragali based on morphological and molecular analysis, thereby fulfilling Koch's postulates. No report on the occurrence of powdery mildew on S. salsula plants has been found previously. The occurrence of this destructive powdery mildew may adversely affect the cultivation of S. salsula. Identifying the pathogen of powdery mildew will support future efforts to control and manage powdery mildew on S. salsula.

Meta-Prism: Ultra-fast and highly accurate microbial community structure search utilizing dual indexing and parallel computation.

Microbiome samples are accumulating at an unprecedented speed. As a result, a massive amount of samples have become available for the mining of the intrinsic patterns among them. However, due to the lack of advanced computational tools, fast yet accurate comparisons and searches among thousands to millions of samples are still in urgent need. In this work, we proposed the Meta-Prism method for comparing and searching the microbial community structures amongst tens of thousands of samples. Meta-Prism is at least 10 times faster than contemporary methods serving the same purpose and can provide very accurate search results. The method is based on three computational techniques: dual-indexing approach for sample subgrouping, refined scoring function that could scrutinize the minute differences among samples, and parallel computation on CPU or GPU. The superiority of Meta-Prism on speed and accuracy for multiple sample searches is proven based on searching against ten thousand samples derived from both human and environments. Therefore, Meta-Prism could facilitate similarity search and in-depth understanding among massive number of heterogenous samples in the microbiome universe. The codes of Meta-Prism are available at: https://github.com/HUST-NingKang-Lab/metaPrism.

Assessment of Cerebral White Matter Involvement in Amyotrophic Lateral Sclerosis Patients With Disease Progression and Cognitive Impairment by Fixel-Based Analysis and Neurite Orientation Dispersion and Density Imaging.

BACKGROUND: Previous studies using emerging diffusion MRI techniques have revealed damage to the white matter (WM) microstructure in amyotrophic lateral sclerosis (ALS), particularly the influence of crossed fibers, but there is a lack of subgroup analyses. PURPOSE: To detect WM microstructural changes in ALS patients using fixel-based analysis (FBA) and neurite orientation dispersion and density imaging (NODDI) MRI. STUDY TYPE: Prospective. POPULATION: Thirty-six ALS patients (aged 60.50 ± 9.5 years) and 25 healthy controls (HCs) (aged 58.90 ± 8.1 years). FIELD STRENGTH/SEQUENCE: 3 T; NODDI and FBA (b-values = 0, 1000, and 2500 seconds/mm2 ). ASSESSMENT: Subgroups were performed according to progression rate and cognition, including fast and slow progression (FP/SP), ALS with and without cognitive impairment (ALS-ci/ALS-nci). Fiber density (FD), fiber-bundle cross-section (FC), combined fiber density and cross-section (FDC), neurite density index (NDI), orientation dispersion index (ODI), isotropic volume fraction (ISO), and fractional anisotropy (FA) were calculated and their correlation with clinical variables examined. STATISTICAL TESTING: Chi-square test, Mann-Whitney U test, two-sample t test, partial correlation analysis, and false discovery rate (FDR) corrected. A P-value <0.05 was considered significant. RESULTS: ALS patients had lower FD and FDC values predominantly in the corticospinal tract (CST) and corpus callosum (CC) regions, as well as lower NDI value in the CC, radial crown, and internal capsule compared to HCs. Subgroup analysis based on progression rate and cognitive function showed significant differences in FBA results. The FC in the right CST region was significantly lower in the FP than SP, and the FD in the CC region was significantly lower in the ALS-ci than ALS-nci. Furthermore, a negative correlation was found between the mean FC value and the rate of progression in ALS patients (r = -0.408). DATA CONCLUSION: FBA is a powerful tool for detecting complex cerebral WM microstructural damage for evaluating ALS cognition and disease progression.

The Use of Diffusion Tensor Imaging in the Identification of Acute Rejection and Chronic Allograft Nephropathy After Renal Transplantation.

BACKGROUND: Identifying the cause of renal allograft dysfunction is important for the clinical management of kidney transplant recipients. PURPOSE: To evaluate the diagnostic efficiency of diffusion tensor imaging (DTI) for identifying allografts with acute rejection (AR) and chronic allograft nephropathy (CAN). STUDY TYPE: Prospective. SUBJECTS: Seventy-seven renal transplant patients (aged 42.5 ± 9.5 years), including 29 patients with well-functioning stable allografts (Control group), 25 patients diagnosed with acute rejection (AR group), and 23 patients diagnosed with chronic allograft nephropathy (CAN group). FIELD STRENGTH/SEQUENCE: 1.5 T/T2-weighted imaging and DTI. ASSESSMENT: The serum creatinine, proteinuria, pathologic results, and fractional anisotropy (FA) values were obtained and compared among the three groups. STATISTICAL TEST: One-way analysis of variance; correlation analysis; independent-sample t-test; intraclass correlation coefficients and receiver operating characteristic curves. Statistical significance was set to a P-value <0.05. RESULTS: The AR and CAN groups presented with significantly elevated serum creatinine as compared with the Control group (191.8 ± 181.0 and 163.1 ± 115.8 µmol/L vs. 82.3 ± 20.9 µmol/L). FA decreased in AR group (cortical/medullary: 0.13 ± 0.02/0.31 ± 0.07) and CAN group (cortical/medullary: 0.11 ± 0.02/0.27 ± 0.06), compared with the Control group (cortical/medullary: 0.15 ± 0.02/0.35 ± 0.05). Cortical FA in the AR group was higher than in the CAN group. The area under the curve (AUC) for identifying AR from normal allografts was 0.756 and 0.744 by cortical FA and medullary FA, respectively. The AUC of cortical FA and medullary FA for differentiating CAN from normal allografts was 0.907 and 0.830, respectively. The AUC of cortical FA and medullary FA for distinguishing AR and CAN from normal allografts was 0.828 and 0.785, respectively. Cortical FA was able to distinguish between AR and CAN with an AUC of 0.728. DATA CONCLUSION: DTI was able to detect patients with dysfunctional allografts. Cortical FA can further distinguish between AR and CAN. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Adsorption Kinetics of Poly(benzyl acrylate) Chains onto Alumina Interface during the Flow-Driven Translocation through Cylindrical Nanochannels.

In this work, the adsorption kinetics of the PBAN/AAO system under flushing condition has been investigated, where PBAN and AAO represent poly(benzyl acrylate) and anodic alumina oxide (AAO, average pore radius R0 ≈ 10 nm) nanochannel, respectively. Our specially designed double-pump flushing system is proved to eliminate the overshoot phenomenon and in situ monitor transmembrane pressure (ΔP) as a function of flushing time (t) and flow rate (Q), which gives the effective pore radius (R), cross-sectional coverage factor (χ = [1 - (R/R0)2]), and characteristic ratio (rc) of the increments of χ during each adsorption/desorption cycle at a given bulk solution concentration (Cbulk). Our findings include: (1) by gradient increasing Cbulk from 10 to 200 mg/L at Q = 10 mL/h, the shortest PBA40 displays a saturation adsorption behavior when Cbulk ≥ 80 mg/L and t ≥ 2000 s, which agrees well with the prediction of blob model, whereas for the longer PBAN chains, the chain length (N) and concentration-dependent adsorption tendency get stronger as N increases from 40 to 620 at t ≥ 2000 s, in particular, R/R0 ∼ N-0.20 is observed at Cbulk = 140 mg/L; (2) by focusing on the platform χ in the saturation adsorption regime (χsat), the longer PBAN displays a stronger adsorption trend with partially reversible feature at Q = 5.0 mL/h, namely, as N increases from 40 to 620, χsat increases from 0.15 to 0.83 at Cbulk = 100 mg/L, where rc changes from 0.25 ± 0.10 to 0.80 ± 0.10 as the adsorption/desorption flushing cycle increases from 1 to 8 at Cbulk = 100 mg/L; (3) by further assuming a solvent nonpenetrating and nondraining adsorption layer, χsat determined in the case of curved surface can be comparable to the physical meaning of adsorption thickness (Δad) in the case of flat-surface adsorption, and the fitting result indicates χsat ∼ Δad ∼ N0.58, falling between Δad ∼ N1/2 and Δad ∼ N1.0 predicted by the mean-field and scaling theories for real multichain adsorption, respectively. Overall, the present work not only clarifies some controversies but also provides unambiguous evidence supporting the existence of tightly adsorbed internal and loosely adsorbed external layers.

Gd-EOB-DTPA-enhanced MRI radiomics to predict vessels encapsulating tumor clusters (VETC) and patient prognosis in hepatocellular carcinoma.

OBJECTIVES: The study was to develop a Gd-EOB-DTPA-enhanced MRI radiomics model for preoperative prediction of VETC and patient prognosis in hepatocellular cancer (HCC). METHODS: The study included 182 (training cohort: 128; validation cohort: 54) HCC patients who underwent preoperative Gd-EOB-DTPA-enhanced MRI. Volumes of interest including intratumoral and peritumoral regions were manually delineated in the hepatobiliary phase images, from which 1316 radiomics features were extracted. The least absolute shrinkage and selection operator (LASSO) and multivariable logistic regression were used to select the useful features. Clinical, intratumoral, peritumoral, combined radiomics, and clinical radiomics models were established using machine learning algorithms. The Kaplan-Meier survival analysis was used to assess early recurrence and progression-free survival (PFS) in the VETC + and VETC- patients. RESULTS: In the validation cohort, the area under the curves (AUCs) of radiomics models were higher than that of the clinical model using random forest (all p < 0.05). The peritumoral radiomics model (AUC = 0.972;95% confidence interval [CI]:0.887-0.998) had significantly higher AUC than intratumoral model (AUC = 0.919; 95% CI: 0.811-0.976) (p = 0.044). There were no significant differences in AUC between intratumoral or peritumoral radiomics model (PR) and combined radiomics model (p > 0.05). Early recurrence and PFS were significantly different between the PR-predicted VETC + and VETC- HCC patients (p < 0.05). PR-predicted VETC was independent predictor of early recurrence (hazard ratio [HR]: 2.08[1.31-3.28]; p = 0.002) and PFS (HR: 1.95[1.20-3.17]; p = 0.007). CONCLUSIONS: The intratumoral or peritumoral radiomics model may be useful in predicting VETC and patient prognosis preoperatively. The peritumoral radiomics model may yield an incremental value over intratumoral model. KEY POINTS: • Radiomics models are useful for predicting vessels encapsulating tumor clusters (VETC) and patient prognosis preoperatively. • Peritumoral radiomics model may yield an incremental value over intratumoral model in prediction of VETC. • Peritumoral radiomics-model-predicted VETC was an independent predictor of early recurrence and progression-free survival.

Design, synthesis, and evaluation of phenylpiperazine-phenylacetate derivatives as rapid recovery hypnotic agents.

In this paper, we designed and synthesized a series of novel phenylpiperazine-phenylacetate derivatives as rapid recovery hypnotic agents. The best compound 10 had relatively high affinity for the GABAA receptor and low affinity for thirteen other off-target receptors. In three animal models (mice, rats, and rabbits), compound 10 exerted potent hypnotic effects (HD50 = 5.2 mg/kg in rabbits), comparable duration of the loss of righting reflex (LORR), and significant shorter recovery time (time to walk) than propanidid. Furthermore, compound 10 (TI = 18.1) showed higher safety profile than propanidid (TI = 14.7) in rabbits. Above results suggested that compound 10 may have predictable and rapid recovery profile in anesthesia.

Discovery of a novel class of benzoxazole derivatives as histamine H3 receptor ligands for the treatment of neuropathic pain.

To discover effective analgesics, we summarize the synthesis, optimization, and pharmacological anti-nociceptive effects of a novel series of benzoxazole derivatives targeting H3 receptor (H3R). The new benzoxazoles were assayed in vitro for histamine H3R and H1R binding affinity. The best compound 8d (2-methyl-6-(3-(4-methylpiperazin-1-yl)propoxy)benzo[d]oxazole) exhibited high affinity for H3R (Ki = 19.7 nM), high selectivity for ten other off-target receptors, and negligible effects on human ether-a-go-go-related gene (hERG, cardiac ion channel). In rodent animals, compound 8d dose-dependently reversed formalin-evoked pain (Phase I, ED50 = 6.0 mg/kg; Phase II, ED50 = 7.8 mg/kg) and CCI-induced neuropathic pain (chronic constriction injury, ED50 = 15.6 mg/kg). Furthermore, compound 8d showed an excellent safety profile in acute toxicity test (LD50 > 2000 mg/kg) with a therapeutic index (TI = LD50/ED50) > 250 and showed a desirable drug-like pharmacokinetic profile. Above characteristics indicate that compound 8d represents a promising candidate analgesic for the treatment of neuropathic pain.

Perineural invasion, lactate dehydrogenase, globulin, and serum sodium predicting occult metastasis in oral cancer.

OBJECTIVE: This study aimed to develop a nomogram to predict the neck occult metastasis in early (T1-T2 cN0) oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: The nomogram was developed in a training cohort of 336 early OSCC patients and was validated in a validation cohort including 88 patients. Independent predictors were calculated by univariate and multivariate logistic regression analyses. RESULTS: In univariate logistical regression analysis, gender, perineural invasion (PNI), blood vessel invasion, mean corpuscular hemoglobin, aspartate aminotransferase, prealbumin, globulin (GLO), lactate dehydrogenase (LDH), serum sodium (NA), and serum chloride were significant associated with neck occult metastasis. Multivariate logistical regression analysis identified PNI (p < .001), LDH (p = .003), GLO (p = .019), and NA (p = .020) as independent predictors of neck occult metastasis. Cut-off values for LDH, GLO, and NA obtained from AUC were 142.5, 26.35, and 139.5, respectively. The nomogram based on PNI and categorical GLO, LDH, and NA exhibited a strong discrimination, with a C-indexes of 0.748 (95%CI = 0.688 to 0.810) in the training cohort and 0.751 (95%CI = 0.639 to 0.863) in the validation cohort. CONCLUSIONS: A nomogram based on PNI, LDH, GLO, and NA for predicting the risk of neck lymph nodes occult metastasis in OSCC could help surgeons with therapy decision-making.

He-Ne laser irradiation ameliorates cadmium toxicity in wheat by modulating cadmium accumulation, nutrient uptake and antioxidant defense system.

Cadmium (Cd) is one of the most hazardous heavy metals that negatively affect the growth and yield of wheat. He-Ne laser irradiation is known to ameliorate cadmium (Cd) stress in wheat. However, the underlying mechanism of He-Ne laser irradiation on protecting wheat against Cd stress is not well recognized. In present study, Cd-treated wheat showed significant reduction in growth, root morphology and total chlorophyll content, but notably increase of Cd accumulation in both roots and shoots. However, He-Ne laser irradiation dramatically reduced concentrations of malondialdehyde (MDA) and hydrogen peroxide (H2O2), and increased total chlorophyll content and activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX) in roots of wheat plants under Cd stress. Further, He-Ne laser irradiation significantly upregulated the transcripts of TaGR (glutathione reductase) and TaGST (glutathione-S-transferase) genes along with the increased activities of GR and GST and glutathione (GSH) concentration in roots of wheat seedlings under Cd stress. In addition, He-Ne laser irradiation enhanced the uptake of mineral elements (N, P, Mg, Fe, Zn and Cu), and significantly decreased Cd uptake and transport mainly through down-regulating the expressions of Cd transport genes (TaHMA2 and TaHMA3) in roots of wheat seedlings under Cd stress. Overall, these findings suggested that He-Ne laser irradiation alleviated the adverse effects of Cd on wheat growth by enhancing antioxidant defense system, improving mineral nutrient status, and decreasing the Cd uptake and transport. This study provides new insights into the roles of He-Ne laser irradiation in the amelioration of Cd stress in wheat and indicates the potential application of this irradiation in crop breeding and growth under Cd stress conditions.

First report of Podosphaera fusca Causing Powdery Mildew on Coreopsis lanceolata in China.

Coreopsis lanceolata, known as lance-leaf coreopsis, is a perennial plant with high ornamental value. It is widely grown in many public parks and home gardens in China due to its showy flowers. From May to June 2020, typical powdery mildew-signs and symptoms were seen on leaves of C. lanceolata cultivated in the east campus of Henan Normal University, Henan Province, China. Abundant white powder-like masses in spot- or coalesced-lesions were on ad- and abaxial surfaces of plant leaves and covered up to 50 % of the leaf area. The infected leaves were deformed and eventually prematurely senescent. Approximately 80 % of observed C. lanceolata plants showed these signs and symptoms. Unbranched conidiophores (n = 25) were 90 to 200 × 12 to 20 µm and showed a foot cell, followed by 1 to 3 short cells and conidia. Ellipsoid-ovoid shaped conidia (n = 30) were 22 to 36 × 15 to 23 µm, with a length/width ratio of 1.4 to 2.4. No chasmothecia were detected. The powdery mildew fungus was initially identified as Podosphaera fusca based on the morphological characteristics. Total genomic DNA of the pathogen was extracted and the rDNA internal transcribed spacer (ITS) region was amplified and sequenced using the primers ITS1/ITS4 (White et al. 1990; Zhu et al. 2019). The obtained sequence was deposited into GenBank under Accession No. MT899186 and was 100 % identical to P. fusca (JX546297) from Herba eupatorii (Ding et al. 2013). To perform pathogenicity assays, leaf surface of three healthy plants was inoculated with fungal conidia according to a previously described method (Zhu et al. 2021). As a control, three non-inoculated plants were used. The control and inoculated plants were placed separately in two growth chambers (light/dark, 16 h/8 h; humidity, 65 %; temperature, 20 ℃). Fourteen- to sixteen-days post inoculation, powdery mildew signs were noticed on inoculated plants, whereas control remained asymptomatic. Similar results were found by performing two repeated pathogenicity assays. Therefore, based on the morphological and molecular analysis, the pathogen was identified and confirmed as P. fusca. This fungus has been reported on C. lanceolata in Korea (Park et al. 2010) and Italy (Garibaldi et al. 2007). This is, to the best of our knowledge, the first report of P. fusca on C. lanceolata in China. The sudden occurrence of this powdery mildew disease on C. lanceolata may adversely affect the health of valuable ornamentals in China. The precise identification of the causal agent of this powdery mildew of C. lanceolata is a preliminary step in developing effective disease management strategies.

Temporal expression study of miRNAs in the crown tissues of winter wheat grown under natural growth conditions.

BACKGROUND: Winter wheat requires prolonged exposure to low temperature to initiate flowering (vernalization). Shoot apical meristem of the crown is the site of cold perception, which produces leaf primordia during vegetative growth before developing into floral primordia at the initiation of the reproductive phase. Although many essential genes for winter wheat cold acclimation and floral initiation have been revealed, the importance of microRNA (miRNA) meditated post-transcriptional regulation in crowns is not well understood. To understand the potential roles of miRNAs in crown tissues, we performed a temporal expression study of miRNAs in crown tissues at the three-leaf stage, winter dormancy stage, spring green-up stage, and jointing stage of winter wheat grown under natural growth conditions. RESULTS: In total, 348 miRNAs belonging to 298 miRNA families, were identified in wheat crown tissues. Among them, 92 differentially expressed miRNAs (DEMs) were found to be significantly regulated from the three-leaf stage to the jointing stage. Most of these DEMs were highly expressed at the three-leaf stage and winter dormancy stage, and then declined in later stages. Six DEMs, including miR156a-5p were markedly induced during the winter dormancy stage. Eleven DEMs, including miR159a.1, miR390a-5p, miR393-5p, miR160a-5p, and miR1436, were highly expressed at the green-up stage. Twelve DEMs, such as miR172a-5p, miR394a, miR319b-3p, and miR9676-5p were highly induced at the jointing stage. Moreover, 14 novel target genes of nine wheat or Pooideae-specific miRNAs were verified using RLM-5' RACE assay. Notably, six mTERFs and two Rf1 genes, which are associated with mitochondrial gene expression, were confirmed as targets of three wheat-specific miRNAs. CONCLUSIONS: The present study not only confirmed the known miRNAs associated with phase transition and floral development, but also identified a number of wheat or Pooideae-specific miRNAs critical for winter wheat cold acclimation and floral development. Most importantly, this study provided experimental evidence that miRNA could regulate mitochondrial gene expression by targeting mTERF and Rf1 genes. Our study provides valuable information for further exploration of the mechanism of miRNA mediated post-transcriptional regulation during winter wheat vernalization and inflorescent initiation.

LAZY1 Controls Tiller Angle and Shoot Gravitropism by Regulating the Expression of Auxin Transporters and Signaling Factors in Rice.

Tiller angle is a key factor determining rice plant architecture, planting density, light interception, photosynthetic efficiency, disease resistance and grain yield. However, the mechanisms underlying tiller angle control are far from clear. In this study, we identified a mutant, termed bta1-1, with an enlarged tiller angle throughout its life cycle. A detailed analysis reveals that BTA1 has multiple functions because tiller angle, shoot gravitropism and tolerance to drought stress are changed in bta1-1 plants. Moreover, BTA1 is a positive regulator of shoot gravitropism in rice. Shoot responses to gravistimulation are disrupted in bta1-1 under both light and dark conditions. Gene cloning reveals that bta1-1 is a novel mutant allele of LA1 renamed la1-SN. LA1 is able to rescue the tiller angle and shoot gravitropism defects observed in la1-SN. The nuclear localization signal of LA1 is disrupted by la1-SN, causing changes in its subcellular localization. LA1 is required to regulate the expression of auxin transporters and signaling factors that control shoot gravitropism and tiller angle. High-throughput mRNA sequencing is performed to elucidate the molecular and cellular functions of LA1. The results show that LA1 may be involved in the nucleosome and chromatin assembly, and protein-DNA interactions to control gene expression, shoot gravitropism and tiller angle. Our results provide new insight into the mechanisms whereby LA1 controls shoot gravitropism and tiller angle in rice.