StMAPK10 gene functional identification and analysis in drought resistance of potato crop (Solanum tuberosum L.).

All over the world, potato (Solanum tuberosum L.) production is constrained by several biotic and abiotic factors. Many techniques and mechanisms have been used to overcome these hurdles and increase food for the rising population. In crop plants, the mitogen-activated protein kinase (MAPK) cascade, a significant regulator of the MAPK pathway under various biotic and abiotic stress conditions, is one of the targets to increase productivity. MAPK plays a significant role under drought stress in potato. However, the function of MAPK in drought resistance in potato is poorly understood. In this study, we wanted to identify the function of StMAPK10 in the drought resistance in potato. StMAPK10 was up-regulated under drought conditions and dynamically modulated by abiotic stresses. Over-expression and down-regulation of StMAPK10 revealed that StMAPK10 stimulated potato growth under drought conditions, as demonstrated by changes in SOD, CAT, and POD activity, as well as H2O2, proline, and MDA content. StMAPK10 up-regulation exaggerated the drought resistance of the potato plant by uplifting antioxidant activities and photosynthetic indices. Overexpressed-StMAPK10 potato lines showed highly significant results for physiological and photosynthetic indices in response to drought stress, while knockdown expression showed opposite outcomes. Additionally, subcellular localization and phenotypic analysis of transgenic and non-transgenic plants substantiated the role of the increased expression of StMAPK10 against drought stress. The results could provide novel insights into the functionality of StMAPK10 in drought responses and conceivable mechanisms.

Control of Plant Height and Lateral Root Development via Stu-miR156 Regulation of SPL9 Transcription Factor in Potato.

MicroRNAs (miRNAs) are a class of endogenous, non-coding small-molecule RNAs that usually regulate the expression of target genes at the post-transcriptional level. miR156 is one of a class of evolutionarily highly conserved miRNA families. SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factor is one of the target genes that is regulated by miR156. SPL transcription factors are involved in regulating plant growth and development, hormone response, stress response, and photosynthesis. In the present study, transgenic potato plants with overexpressed miR156 were obtained via the Agrobacterium-mediated transformation method. The results showed that the expression levels of the target gene, StSPL9, were all downregulated in the transgenic plants with overexpressed Stu-miR156. Compared with those of the control plants, the plant height and root length of the transgenic plants were significantly decreased, while the number of lateral roots was significantly increased. These results revealed that the miR156/SPLs module was involved in regulating potato plant height and root growth.

Evaluating AAPM-TG-218 recommendations: Gamma index tolerance and action limits in IMRT and VMAT quality assurance using SunCHECK.

PURPOSE: This study aimed to improve the safety and accuracy of radiotherapy by establishing tolerance (TL) and action (AL) limits for the gamma index in patient-specific quality assurance (PSQA) for intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) using SunCHECK software, as per AAPM TG-218 report recommendations. METHODS: The study included 125 patients divided into six groups by treatment regions (H&N, thoracic and pelvic) and techniques (VMAT, IMRT). SunCHECK was used to calculate the gamma passing rate (%GP) and dose error (%DE) for each patient, for the planning target volume and organs at risk (OARs). The TL and AL were then determined for each group according to TG-218 recommendations. We conducted a comprehensive analysis to compare %DE among different groups and examined the relationship between %GP and %DE. RESULTS: The TL and AL of all groups were more stringent than the common standard as defined by the TG218 report. The TL and AL values of the groups differed significantly, and the values for the thoracic groups were lower for both VMAT and IMRT. The %DE of the parameters D95%, D90%, and Dmean in the planning target volume, and Dmean and Dmax in OARs were significantly different. The dose deviation of VMAT was larger than IMRT, especially in the thoracic group. A %GP and %DE correlation analysis showed a strong correlation for the planning target volume, but a weak correlation for the OARs. Additionally, a significant correlation existed between %GP of SunCHECK and Delta4. CONCLUSION: The study established TL and AL values tailored to various anatomical regions and treatment techniques at our institution. Establishing PSQA workflows for VMAT and IMRT offers valuable clinical insights and guidance. We also suggest developing a standard combining clinically relevant metrics with %GP to evaluate PSQA results comprehensively.

Clinical Value of 68Ga-Pentixafor PET/CT in Subtype Diagnosis of Primary Aldosteronism Patients with Adrenal Micronodules.

Our objective was to investigate the clinical value of 68Ga-pentixafor PET/CT in subtype diagnosis of primary aldosteronism (PA) patients with adrenal micronodules less than 1 cm in diameter and compare it with the routine clinical methods. Methods: We used prospective enrollment of PA patients with adrenal micronodules identified by adrenal CT scans to undergo 68Ga-pentixafor PET/CT. Patients were divided into surgically eligible and ineligible groups based on surgical pathology and postoperative follow-up or adrenal venous sampling (AVS) results. Patient management was discussed by a multidisciplinary team. The semiquantitative parameters of PET/CT included SUVmax for adrenal lesion and SUV ratios for lesion to liver and lesion to normal adrenal gland. Results: In total, 123 PA patients with adrenal micronodules were examined using 68Ga-pentixafor PET/CT, and 104 patients who underwent surgery or successful AVS were included in the analysis (48 ± 10 y old). The sensitivity, specificity, and accuracy of visual analysis using 68Ga-pentixafor PET/CT to identify surgically eligible patients were 90.2%, 72.7%, and 86.5%, respectively, which were significantly higher than those of adrenal CT (73.1%, 53.8%, and 68.3%, respectively) and yielded consistent results in different CT morphologic or age subgroups. In 36 patients who had both AVS and 68Ga-pentixafor PET/CT, the tests showed a 66.7% concordance rate. However, PET/CT was significantly more concordant with surgical outcomes than was AVS in 17 patients who underwent adrenalectomy (82.4% vs. 68.86%). Among the 183 adrenal micronodules included in the study, the semiquantitative diagnostic thresholds for 92 lesions eligible for surgical treatment were an SUVmax of at least 4.55, an SUV ratio of at least 2.17 for lesion to liver, and an SUV ratio of at least 1.90 for lesion to normal adrenal gland. All patients benefited from surgical removal of 68Ga-pentixafor-avid microlesions. Conclusion: In PA patients with adrenal micronodules, 68Ga-pentixafor PET/CT demonstrated promising diagnostic accuracy in classification and appeared to perform better than adrenal CT. Furthermore, there was also a suggestion of some potential in predicting postoperative efficacy compared with AVS, although these observations require further investigation and verification in larger cohorts.

Metformin ameliorates liver fibrosis induced by congestive hepatopathy via the mTOR/HIF-1α signaling pathway.

INTRODUCTION AND OBJECTIVES: Congestive hepatopathy (CH) is a hepatic vascular disease that results in chronic liver congestion, which can lead to liver fibrosis. New uses of metformin have been discovered over the years. However, the function of metformin in congestive liver fibrosis is not yet fully understood. This study aimed to investigate the effect of metformin on liver fibrosis in a mouse model of CH. MATERIALS AND METHODS: Partial ligation of the inferior vena cava (pIVCL) was used to establish a mouse model of liver congestion. Metformin (0.1%) was added to the daily drinking water of the animals, and the effect of metformin on liver tissue was studied after 6 weeks. Hepatic stellate cells (HSCs) were also stimulated with CoCl2 to investigate the inhibitory impact of metformin on the mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) pathway. RESULTS: Metformin attenuated liver congestion; decreased the expression of collagen, fibronectin, α-smooth muscle actin (α-SMA), and HIF-1α; and ameliorated liver fibrosis in pIVCL mice. The proliferation and migration of HSCs were inhibited by metformin in vitro, which prevented α-SMA expression and restrained HSC activation. The expression levels of phosphorylated-mTOR, HIF-1α, and vascular endothelial growth factor were also decreased. CONCLUSIONS: Metformin inhibits CH-induced liver fibrosis. Functionally, this beneficial effect may be the result of inhibition of HSC activation and of the mTOR/HIF-1α signaling pathway.

Baseline neutrophil-to- ratio combined with the change during treatment provides risk stratification for metastatic malignant melanoma patients treated with PD-1 inhibitors in a Chinese population.

Background: Previous studies have suggested that an elevated baseline neutrophil-to-lymphocyte ratio (BLNLR) and elevated relative change of NLR (ΔNLR%) is associated with worse outcomes in patients with a variety of cancers. This study aims to investigate the value of BLNLR and ΔNLR% before the third cycle of treatment on the prognosis of patients with metastatic malignant melanoma treated with PD-1 inhibitors. Methods: A total of 63 patients with metastatic malignant melanoma treated with PD-1 inhibitors in the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2021 were retrospectively analyzed. BLNLR and ΔNLR% before the third cycle of treatment were collected. The Kaplan-Meier method was used to draw survival curves and Log-Rank test was used for survival analysis. Univariate and multivariate Cox regression analysis were used to analyze the relationship between BLNLR, ΔNLR% and clinical characteristics with progression-free survival (PFS) and overall survival (OS). Results: Univariate analysis showed that PFS and OS were associated with BLNLR, ΔNLR%, BMI and number of metastatic organs (P < 0.05). Multivariate analysis showed that BLNLR, ΔNLR%, BMI and number of metastatic organs were independent predictors of OS and BLNLR and ΔNLR% were independent predictors of PFS. Patients were divided into four groups according to BLNLR (<3, ≥3) and ΔNLR% (< 30%, ≥30%): low-BLNLR + low-ΔNLR% group, low-BLNLR + high-ΔNLR% group, high-BLNLR + low-ΔNLR% group, high-BLNLR + high-ΔNLR% group. The median OS was 20 months, 8 months, 9 months, 5 months and the median PFS was 8 months, 3 months, 2 months, 2 months, respectively. Conclusion: BLNLR combined with ΔNLR% can be used to predict the prognosis of PD-1 inhibitors in patients with metastatic malignant melanoma.

Synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome with cranial bone involvement: Case report and literature review.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare autoimmune inflammatory disease characterized by osteoarticular and dermatological manifestations. The most common osteoarticular manifestations involve the anterior chest wall, axial skeleton, and long bones. Cranial bone involvement is less reported in SAPHO syndrome. We herein present three cases of SAPHO syndrome with cranial bone involvement, and review the previous literature on similar manifestations. It was revealed that SAPHO syndrome could lead to cranial bone involvement, which could involve the dura mater, leading to hypertrophic pachymeningitis, but the outcome is usually good. Janus kinase inhibitors may be a potential treatment option.

Development of a prognostic scoring system for hepatic vena cava Budd-Chiari syndrome with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a serious complication of hepatic vena cava Budd-Chiari syndrome (HVC-BCS) that significantly reduces the survival time of patients. Our study aimed to analyze the prognostic factors influencing the survival of HVC-BCS patients with HCC and to develop a prognostic scoring system. METHODS: The clinical and follow-up data of 64 HVC-BCS patients with HCC who received invasive treatment at the First Affiliated Hospital of Zhengzhou University between January 2015 and December 2019 were retrospectively analyzed. Kaplan-Meier curves and log-rank tests were used to analyze the survival curve of patients and the difference in prognoses between the groups. Univariate and multivariate Cox regression analyses were performed to analyze the influence of biochemical, tumor, and etiological characteristics on the total survival time of patients, and a new prognostic scoring system was developed according to the regression coefficients of the independent predictors in the statistical model. The prediction efficiency was evaluated using the time-dependent receiver operating characteristics curve and concordance index. RESULTS: Multivariate analysis showed that serum albumin level < 34 g/L [hazard ratio (HR) = 4.207, 95% confidence interval (CI): 1.816-8.932, P = 0.001], maximum tumor diameter > 7 cm (HR = 3.612, 95% CI: 1.646-7.928, P = 0.001), and inferior vena cava stenosis (HR = 8.623, 95% CI: 3.771-19.715, P < 0.001) were independent predictors of survival. A prognostic scoring system was developed according to the above-mentioned independent predictors, and patients were classified into grades A, B, C and D. Significant differences in survival were found among the four groups. CONCLUSIONS: This study successfully developed a prognostic scoring system for HVC-BCS patients with HCC, which is helpful for clinical evaluation of patient prognosis.

Synovitis, acne, pustulosis, hyperostosis and osteitis syndrome with mandibular involvement: Would surgical operation help?

BACKGROUND: Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome is a rare autoinflammatory disease; its primary manifestation includes osteoarthropathy with skin involvement. Janus kinase (JAK) inhibitors, such as tofacitinib, were used for rheumatoid arthritis; however, due to its downregulation of immune cytokines including interleukin (IL)-6 and IL-8, it might be effective for SAPHO patients. CASE SUMMARY: We report the 1st case of mandibular-related SAPHO syndrome treated with tofacitinib. The patient underwent mandibular resection surgery twice and postoperative pathology showed "osteomyelitis". The patient developed sclerosing osteomyelitis in the left wrist 9 months after surgery and SAPHO syndrome was diagnosed. The patient was administered nonsteroidal anti-inflammatory drugs and corticosteroids therapy without much remission. A 3-month tofacitinib therapy provided remission from both systemic inflammation status and peripheral osteoarticular symptoms and no significant recurrence was observed during follow-up in this case. CONCLUSION: Mandibular involvement in SAPHO syndrome is easily misdiagnosed due to its rarity. Mandibular resection surgery should be applied carefully; after systemic treatment with tofacitinib, the patient had remission. We provide a successful experience for the treatment of mandibular-related SAPHO syndrome.

Stu-miR827-Targeted StWRKY48 Transcription Factor Negatively Regulates Drought Tolerance of Potato by Increasing Leaf Stomatal Density.

Stomata are specialized portals in plant leaves to modulate water loss from plants to the atmosphere by control of the transpiration, thereby determining the water-use efficiency and drought resistance of plants. Despite that the stomata developmental progression is well-understood at the molecular level, the experimental evidence that miRNA regulates stomata development is still lacking, and the underlying mechanism remains elusive. This study demonstrates the involvement of stu-miR827 in regulating the drought tolerance of potato due to its control over the leaf stomatal density. The expression analysis showed that stu-miR827 was obviously repressed by drought stresses and then rapidly increased after rewatering. Suppressing the expression of stu-miR827 transgenic potato lines showed an increase in stomatal density, correlating with a weaker drought resistance compared with wildtype potato lines. In addition, StWRKY48 was identified as the target gene of stu-miR827, and the expression of StWRKY48 was obviously induced by drought stresses and was greatly upregulated in stu-miR827 knockdown transgenic potato lines, suggesting its involvement in the drought stress response. Importantly, the expression of genes associated with stomata development, such as SDD (stomatal density and distribution) and TMM (too many mouths), was seriously suppressed in transgenic lines. Altogether, these observations demonstrated that suppression of stu-miR827 might lead to overexpression of StWRKY48, which may contribute to negatively regulating the drought adaptation of potato by increasing the stomatal density. The results may facilitate functional studies of miRNAs in the process of drought tolerance in plants.

StTCP15 regulates potato tuber sprouting by modulating the dynamic balance between abscisic acid and gibberellic acid.

The major stages of the potato life cycle are tuber dormancy and sprouting, however, there is still known very little of the mechanisms that control these processes. TCP (Theosinte branch I, Cycloidea, proliferationcell factors 1 and 2) transcription factors play a key role in plant growth and dormancy related developmental processes. Previous researches demonstrated that TCP transcription factor StTCP15 had a function in the promotion of dormancy. To elucidate the function of StTCP15 gene, it was cloned from potato cultivar "Desiree," which encodes a polypeptide consisting of 414 amino acids and is mainly found in the nucleus. The potato tubers of StTCP15 overexpression lines sprouted in advance, while the potato tubers of StTCP15 down-regulated expression lines showed delayed sprouting. In addition, it was also found that overexpression lines of StTCP15 extremely significantly reduced the ratio of abscisic acid (ABA)/gibberellic acid (GA3), while the superoxide dismutase activity decreased, and the activity of peroxidase and catalase increased compared with the wild type. The opposite result was found in the down-regulated expression lines of StTCP15 gene. Three interacting proteins, StSnRK1, StF-Box and StGID1, were screened by Yeast two-hybrid, and verified by Bimolecular Fluorescence Complementation and Split-luciferase, indicating that StTCP15 could affect ABA and GA3 signaling pathways to regulate potato tuber dormancy and sprouting. Together, these results demonstrated that StTCP15 regulated potato tuber dormancy and sprouting by affecting the dynamic balance between ABA and GA3. The result could provide some information on the molecular mechanism of StTCP15 regulating potato tuber dormancy and sprouting.

Tumor necrosis factor inhibitors for pediatric patients with SAPHO syndrome associated with acne conglobata.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic inflammatory disease with osteoarticular and cutaneous involvements as its main manifestations. Acne conglobata as a severe acne form may affect adolescent patients. Tumor necrosis factor inhibitors are usually used as a second-line therapy for refractory SAPHO syndrome and has been reported to treat acne conglobata successfully. We herein report three cases of adolescent patients with SAPHO syndrome associated with acne conglobata who were successfully treated with TNFi therapy.

Photonic crystal enhanced fluorescence emission and blinking suppression for single quantum dot digital resolution biosensing.

While nanoscale quantum emitters are effective tags for measuring biomolecular interactions, their utilities for applications that demand single-unit observations are limited by the requirements for large numerical aperture (NA) objectives, fluorescence intermittency, and poor photon collection efficiency resulted from omnidirectional emission. Here, we report a nearly 3000-fold signal enhancement achieved through multiplicative effects of enhanced excitation, highly directional extraction, quantum efficiency improvement, and blinking suppression through a photonic crystal (PC) surface. The approach achieves single quantum dot (QD) sensitivity with high signal-to-noise ratio, even when using a low-NA lens and an inexpensive optical setup. The blinking suppression capability of the PC improves the QDs on-time from 15% to 85% ameliorating signal intermittency. We developed an assay for cancer-associated miRNA biomarkers with single-molecule resolution, single-base mutation selectivity, and 10-attomolar detection limit. Additionally, we observed differential surface motion trajectories of QDs when their surface attachment stringency is altered by changing a single base in a cancer-specific miRNA sequence.