A novel mutation in the ABCC8 gene causing maturity-onset diabetes of the young: A case report.

A 34-year-old woman was diagnosed with type 1 diabetes mellitus and treated with insulin for 24 years. The patient has a family history of diabetes in three consecutive generations. Her Whole exon sequencing showed a heterozygous mutation in the ABCC8 gene, and it also found some of her relatives to carry this mutation. She was diagnosed with MODY12 and received glimepiride therapy with the achievement of good glycaemic control.

Synergistic Redox Modulation for High-Performance Nickel Oxide-Based Inverted Perovskite Solar Modules.

Nickel oxide (NiOx )-based inverted perovskite solar cells stand as promising candidates for advancing perovskite photovoltaics towards commercialization, leveraging their remarkable stability, scalability, and cost-effectiveness. However, the interfacial redox reaction between high-valence Ni4+ and perovskite, alongside the facile conversion of iodide in perovskite into I2 , significantly deteriorates the performance and reproducibility of NiOx -based perovskite photovoltaics. Here, potassium borohydride (KBH4 ) is introduced as a dual-action reductant, which effectively avoids the Ni4+ /perovskite interface reaction and mitigates the iodide-to-I2 oxidation within perovskite film. This synergistic redox modulation significantly suppresses nonradiative recombination and increases the carrier lifetime. As a result, an impressive power conversion efficiency of 24.17% for NiOx -based perovskite solar cells is achieved, and a record efficiency of 20.2% for NiOx -based perovskite solar modules fabricated under ambient conditions. Notably, when evaluated using the ISOS-L-2 standard protocol, the module retains 94% of its initial efficiency after 2000 h of continuous illumination under maximum power point at 65 °C in ambient air.

The effect of working memory load on selective attention to emotional faces for social anxiety individuals.

Research has confirmed that individuals with social anxiety (SA) show an attentional bias towards threat-related stimuli. However, the extent to which this attentional bias depends on top-down cognitive control processes remains controversial. The present study investigated the effect of working memory (WM) load on selective attention to emotional faces in both high social anxiety (HSA) and low social anxiety (LSA) groups by manipulating WM load through the inclusion of forward counting in multiples of two (low load) or backward counting in multiples of seven (high load) within a modified flanker task. In the flanker task, emotional faces (angry, happy, or neutral faces) were used as targets and distractors. A total of 70 participants (34 HSA participants; 36 LSA participants) completed the flanker task in the laboratory. The results showed that the HSA individuals performed worse when responding to angry targets. Relative to LSA individuals, HSA individuals showed interference from angry distractors in the flanker task, resulting in significantly lower accuracy in identifying angry targets compared to happy targets. These results were unaffected by the manipulation of WM load. The findings imply HSA individuals have impaired attentional control, and that their threat-related attentional bias relies more on the bottom-up automatic attentional process.

Soybean GmSAUL1, a Bona Fide U-Box E3 Ligase, Negatively Regulates Immunity Likely through Repressing the Activation of GmMPK3.

E3 ubiquitin ligases play important roles in plant immunity, but their role in soybean has not been investigated previously. Here, we used Bean pod mottle virus (BPMV)-mediated virus-induced gene silencing (VIGS) to investigate the function of GmSAUL1 (Senescence-Associated E3 Ubiquitin Ligase 1) homologs in soybean. When two closely related SAUL1 homologs were silenced simultaneously, the soybean plants displayed autoimmune phenotypes, which were significantly alleviated by high temperature, suggesting that GmSAUL1a/1b might be guarded by an R protein. Interestingly, silencing GmSAUL1a/1b resulted in the decreased activation of GmMPK6, but increased activation of GmMPK3 in response to flg22, suggesting that the activation of GmMPK3 is most likely responsible for the activated immunity observed in the GmSAUL1a/1b-silenced plants. Furthermore, we provided evidence that GmSAUL1a is a bona fide E3 ligase. Collectively, our results indicated that GmSAUL1 plays a negative role in regulating cell death and immunity in soybean.

A deep network embedded with rough fuzzy discretization for OCT fundus image segmentation.

The noise and redundant information are the main reasons for the performance bottleneck of medical image segmentation algorithms based on the deep learning. To this end, we propose a deep network embedded with rough fuzzy discretization (RFDDN) for OCT fundus image segmentation. Firstly, we establish the information decision table of OCT fundus image segmentation, and regard each category of segmentation region as a fuzzy set. Then, we use the fuzzy c-means clustering to get the membership degrees of pixels to each segmentation region. According to membership functions and the equivalence relation generated by the brightness attribute, we design the individual fitness function based on the rough fuzzy set, and use a genetic algorithm to search for the best breakpoints to discretize the features of OCT fundus images. Finally, we take the feature discretization based on the rough fuzzy set as the pre-module of the deep neural network, and introduce the deep supervised attention mechanism to obtain the important multi-scale information. We compare RFDDN with U-Net, ReLayNet, CE-Net, MultiResUNet, and ISCLNet on the two groups of 3D retinal OCT data. RFDDN is superior to the other five methods on all evaluation indicators. The results obtained by ISCLNet are the second only inferior to those obtained by RFDDN. DSC, sensitivity, and specificity of RFDDN are evenly 3.3%, 2.6%, and 7.1% higher than those of ISCLNet, respectively. HD95 and ASD of RFDDN are evenly 6.6% and 19.7% lower than those of ISCLNet, respectively. The experimental results show that our method can effectively eliminate the noise and redundant information in Oct fundus images, and greatly improve the accuracy of OCT fundus image segmentation while taking into account the interpretability and computational efficiency.

Vimentin and tumor-stroma ratio for neoadjuvant chemoradiotherapy response prediction in locally advanced rectal cancer.

Vimentin expression in tumor tissues and the tumor-stroma ratio (TSR) have been demonstrated as strong prognostic factors for cancer patients, but whether they are predictive markers of neoadjuvant chemoradiotherapy (nCRT) outcome in locally advanced rectal cancer (LARC) patients is poorly understood. This study aimed to explore the predictive significance of vimentin and TSR combined for nCRT response in LARC patients. Imaging mass cytometry (IMC) was performed to determine the association of vimentin and TSR with nCRT response in six LARC patients [three achieved pathological complete response (pCR), three did not]. Immunohistochemistry (IHC) for vimentin and TSR on biopsy tissues before nCRT and logistic regression analysis were performed to further evaluate their predictive value for treatment responses in a larger patient cohort. A trend of decreased vimentin expression and increased TSR in the pCR group was revealed by IMC. In the validation group, vimentin [odds ratio (OR) 0.260, 95% confidence interval (CI) 0.102-0.602, p = 0.002] and TSR (OR 4.971, 95% CI 1.933-15.431, p = 0.002) were associated with pCR by univariate analysis. Patients in the vimentin-low/TSR-low or vimentin-high/TSR-high (OR 5.211, 95% CI 1.248-35.582, p = 0.042) and vimentin-low/TSR-high groups (OR 11.846, 95% CI 3.197-77.079, p = 0.001) had significantly higher odds of pCR. By multivariate analysis, only the combination of vimentin and TSR was an independent predictor for nCRT response (OR 9.324, 95% CI 2.290-63.623, p = 0.006). Our study suggested that the combined assessment of vimentin and TSR can provide additive significance and may be a promising indicator of nCRT response in LARC patients.

Effects of Dietary Tannic Acid on Obesity and Gut Microbiota in C57BL/6J Mice Fed with High-Fat Diet.

Dietary tannic acid, as a natural polyphenolic, has many important biological activities. This study aimed to investigate the effect of dietary tannic acid on obesity and gut microbiota in mice with a high-fat diet. Male C57BL/6J mice fed a high-fat diet were treated with dietary tannic acid for eight weeks. Results showed that dietary tannic acid reduced the body weight gain, regulated glycolipid metabolism, improved the insulin resistance, and attenuated the liver oxidative stress in high-fat diet-fed mice. Moreover, both dietary tannic acid intervention groups repaired the gut barrier damage caused by a high-fat diet, especially in the 50 mg/kg/d dietary tannic acid intervention group. Interestingly, the effect of dietary tannic acid on serum endotoxin lipopolysaccharide (LPS) content was correlated with the abundance of the LPS-producing microbiota. In addition, dietary tannic acid altered the abundance of obesity-related gut microbiota (Firmicutes, Bacteroidetes, Bacteroides, Alistipes, and Odoribacter) in the 150 mg/kg/d dietary tannic acid intervention group, while it was not effective in the 50 mg/kg/d dietary tannic acid intervention group. These findings suggested the potential effect of dietary tannic acid for the prevention and control of obesity.

Progressive Feature Fusion Attention Dense Network for Speckle Noise Removal in OCT Images.

Although deep learning for Big Data analytics has achieved promising results in the field of optical coherence tomography (OCT) image denoising, the low recognition rate caused by complex noise distribution and a large number of redundant features is still a challenge faced by deep learning-based denoising methods. Moreover, the network with large depth will bring high computational complexity. To this end, we propose a progressive feature fusion attention dense network (PFFADN) for speckle noise removal in OCT images. We arrange densely connected dense blocks in the deep convolution network, and sequentially connect the shallow convolution feature map with the deep one extracted from each dense block to form a residual block. We add attention mechanism to the network to extract the key features and suppress the irrelevant ones. We fuse the output feature maps from all dense blocks and input them to the reconstruction output layer. We compare PFFADN with the state-of-the-art denoising algorithms on retinal OCT images. Experiments show that our method has better improvement in denoising performance.

Bioinformatics Analysis for Identifying Differentially Expressed MicroRNAs Derived from Plasma Exosomes Associated with Radiotherapy Resistance in Non-Small-Cell Lung Cancer.

Objective: To explore the differentially expressed microRNAs (DEmiRs) derived from plasma exosomes related to radiotherapy resistance and their corresponding pathways in non-small-cell lung cancer (NSCLC). Methods: Plasma samples from NSCLC patients were retrieved and analyzed. The patients were divided into 3 groups based on the tumor regression grade criteria, assessed by radiological imaging after radiotherapy. TRG1 referred to tumor shrinkage of ≤30% after radiotherapy, TRG2 as 30% < TRG < 50%, and TRG3 as TRG ≥ 50%. High-throughput sequencing and bioinformatics analysis were used to compare the DEmiRs between the three groups. The miRanda, PITA, and RNAhybrid software were used to identify potential target genes of the DEmiRs. GO function enrichment and KEGG pathway enrichment analyses were performed on the target gene set. Results: There were 24 DEmiRs (12 were upregulated and 12 downregulated) between the TRG1 and TRG2 groups, 11 between the TRG1 and TRG3 groups (6 upregulated and 5 downregulated), and 35 between the TRG2 and TRG3 groups. The common DEmiRs between the three groups were miR-92a-3p. GO analysis showed that the target genes of the DEmiRs were mainly enriched in unicellular organism processes, cell transformation, cell localization, and their establishment. KEGG enrichment analysis showed that target genes were significantly enriched in the Ras signaling pathway and associated with endocytosis. Among the 135 identified target genes of miR-92a-3p, 4 were involved in the PI3K-Akt signaling pathway (the downstream pathway of the Ras gene) and 3 in the cAMP signaling pathway (the upstream pathway of the Ras gene). Further, 2 other target genes were involved in the Rap1 signaling pathway (the upstream pathway of PI3K-Akt). Conclusion: By assessing the expression and functional profile of DEmiRs in the plasma exosomes of NSCLC patients after radiotherapy, miR-92a-3p was identified as a promising target affecting radiotherapy outcomes through the Ras signaling pathway.

Effects of two contrasting dietary polysaccharides and tannic acid on the digestive and physicochemical properties of wheat starch.

In this study, konjac glucomannan, κ-carrageenan, and tannic acid were selected to study the effects of different combinations on the in vitro digestibility and physicochemical properties of wheat starch. Results showed that the addition of konjac glucomannan, κ-carrageenan, and tannic acid could decrease the digestion of starch and increase the content of resistant starch. Besides, the two polysaccharides weakened the extent of tannic acid on starch digestion. Moreover, although the two polysaccharides had different effects on the in vitro digestion of starch, they had no significant increase in the content of resistant starch. DSC and XRD results demonstrated that the polysaccharides and tannic acid showed synergistic effects on the rebuilding of starch microstructure. FTIR results further manifested that κ-carrageenan and konjac glucomannan could significantly increase the strength of hydrogen bonds in starch. At the same time, the addition of tannic acid would weaken the molecular interaction between polysaccharides and starch. SEM and CLSM results showed that tannic acid added to the polysaccharide-starch mixture not only interacted with starch but also influenced the structure of polysaccharide gel.

Immune-related genes LAMA2 and IL1R1 correlate with tumor sites and predict poor survival in pancreatic adenocarcinoma.

Aims: The aim of this study was to identify the immune- and locus-associated genes in pancreatic ductal adenocarcinoma and evaluate their value in prognosis. Methods: The pancreatic ductal adenocarcinoma stromal and immune scores were calculated with the estimation of stromal and immune cells in malignant tumor tissues using expression data algorithm. The authors screened the differentially expressed genes to generate immune- and stromal-related differentially expressed genes. Next, the authors conducted weighted correlation network analysis to find the gene sets related to tumor sites. Results: IL1R1 and LAMA2 were identified as the site- and immune-related genes in pancreatic ductal adenocarcinoma, and their high expression in pancreatic head cancer exhibited high immune scores and predicted unfavorable prognosis. Conclusion: The authors identified IL1R1 and LAMA2 as immune- and locus-associated genes, and their high expression predicted a poor prognosis.

Lay abstract The prognosis of pancreatic cancer is poor, and pancreatic head carcinoma is different from pancreatic body/tail carcinoma in many respects. In recent years, the role of the immune microenvironment in tumors has been increasingly revealed. The authors wanted to find ways to improve the diagnosis and treatment of patients with pancreatic cancer by analyzing the key genes associated with different immune scores and pancreatic cancer sites. In the authors' study, IL1R1 and LAMA2 were identified as immune- and locus-associated genes, and their high expression predicted a poor prognosis, especially in pancreatic body/tail cancer. Early identification of high IL1R1 expression in pancreatic body/tail carcinoma may improve tumor prognosis.

Tuina therapy for temporomandibular joint disorder syndrome: A protocol for systematic review and meta-analysis.

BACKGROUND: Temporomandibular joint disorders (TMD) is common in clinic at present, which seriously affects the mental health and quality of life of patients. With the development of society, the incidence of TMD is gradually increasing. At present, there are many treatment methods, Tuina as a characteristic traditional Chinese medicine therapy, clinical treatment of TMD has a significant effect. In recent years, there are many clinical studies on Tuina in the treatment of TMD, but the clinical efficacy of Tuina in the treatment of TMD has not been systematically evaluated. In this study, we systematically evaluated the relevant literature of Tuina in the treatment of TMD by using the method of evidence-based medicine, in order to provide reference for clinical research in this direction in the future. METHODS: VIP Chinese database, China knowledge Network, Wanfang, China Biomedical Database, PubMed, Embase, Cochrane Library and Web of Science were searched for clinical randomized controlled trials of Tuina in the treatment of TMD from the establishment of the database to December 2020. The 2 researchers independently screened the literature and carried out quality assessment and data extraction for the included study, and used RevMan5.3 software for risk assessment and Meta analysis. RESULTS: In this study, the efficacy and safety of Tuina in the treatment of TMD were evaluated by effective rate, visual analog score (VAS) of temporomandibular joint pain, dysfunction index ((DI), palpation index (PI), craniomandibular index (CMI), maximum mouth opening (MMO), incidence of adverse reactions and so on. CONCLUSION: This protocol can provide evidence-based basis for the treatment of TMD, with Tuina to significantly improve the symptoms and function of patients with TMD. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/J75A8.

Crosstalk between Ubiquitination and Other Post-translational Protein Modifications in Plant Immunity.

Post-translational modifications (PTMs) are central to the modulation of protein activity, stability, subcellular localization, and interaction with partners. They greatly expand the diversity and functionality of the proteome and have taken the center stage as key players in regulating numerous cellular and physiological processes. Increasing evidence indicates that in addition to a single regulatory PTM, many proteins are modified by multiple different types of PTMs in an orchestrated manner to collectively modulate the biological outcome. Such PTM crosstalk creates a combinatorial explosion in the number of proteoforms in a cell and greatly improves the ability of plants to rapidly mount and fine-tune responses to different external and internal cues. While PTM crosstalk has been investigated in depth in humans, animals, and yeast, the study of interplay between different PTMs in plants is still at its infant stage. In the past decade, investigations showed that PTMs are widely involved and play critical roles in the regulation of interactions between plants and pathogens. In particular, ubiquitination has emerged as a key regulator of plant immunity. This review discusses recent studies of the crosstalk between ubiquitination and six other PTMs, i.e., phosphorylation, SUMOylation, poly(ADP-ribosyl)ation, acetylation, redox modification, and glycosylation, in the regulation of plant immunity. The two basic ways by which PTMs communicate as well as the underlying mechanisms and diverse outcomes of the PTM crosstalk in plant immunity are highlighted.

[Impact of abdominal moxibustion in a period of day from 7 am to 9 am on improvement in post-stroke lower limb spasticity and muscle architecture parameter].

OBJECTIVE: To compare the therapeutic effect on post-stroke lower limb spasticity between the combined treatment of abdominal moxibustion from 7 am to 9 am and rehabilitation training and the simple rehabilitation training. METHODS: A total of 100 patients with post-stroke lower limb spasticity were randomized into an observation group (50 cases, 3 cases dropped off) and a control group (50 cases, 4 cases dropped off ). In the control group, the basic treatment of internal medicine and rehabilitation training of the limbs were adopted. In the observation group, on the basis of the treatment in the control group, at the time zone from 7 am to 9 am, moxibustion on the abdomen with "eight-trigram" moxa box [the central moxa box accurately facing Shenque (CV 8)] was given, lasting for 2 h, once every two days. Both groups were treated for 6 weeks. Separately, before and after treatment, the score of Fugl-Meyer assessment of the lower extremity (FMA-LE) and the grade of modified Ashworth scale (MAS) of ankle joint were evaluated on the affected side in patients of the two groups. Muscle skeleton ultrasound (MSUS) was adopted to determine the first layer muscle thickness (MT) anterior to the tibia, the number of pennation angle (PA) and the length of muscle fibers in the medial head of gastrocnemius muscle on the affected side. Besides, after treatment, the therapeutic effect was evaluated in the two groups. RESULTS: After treatment, the score of FMA-LE and the grade of MAS of ankle joint on the affected side were both improved as compared with those before treatment in patients of the two groups (P<0.01, P<0.05). The improvements in the observation group were better than those in the control group (P<0.01, P<0.05). After treatment, MT anterior to the tibia, the number of PA and the length of muscle fibers in the medial head of gastrocnemius muscle on the affected side were all increased as compared with before treatment in patients of the two groups (P<0.01). The increase degree in the observation group was larger than that in the control group (P<0.01). The total effective rate was 93.6% (44/47) in the observation group, better than 80.4% (37/46) in the control group (P<0.05). CONCLUSION: The combined treatment of abdominal moxibustion from 7 am to 9 am and rehabilitation training effectively relieves post-stroke lower limb spasticity and improves the limb functions and muscle structure. The total effective rate of this combined treatment is better than that of simple rehabilitation training.

The influence of Konjac glucomannan on the functional and structural properties of wheat starch.

The aim of this study was to characterize the influence of Konjac glucomannan (KGM) on the functional and structural properties of wheat starch. Results showed that KGM significantly decreased the starch hydrolysis rate, with a lower level of rapidly digestible starch (RDS), and a higher content of slowly digestible starch (SDS). Besides, KGM decreased the content of leached amylose, while enhanced the swelling power, water-holding capacity, freeze-thaw stability, and paste clarity of wheat starch, which indicated a good improvement on the functional properties. Differential scanning calorimetry (DSC) and X-ray diffraction patterns (XRD) manifested that the addition of KGM disrupted the original crystalline structures of wheat starch, which may result in the increased hydrolysis rate of starch. Interestingly, this did not consist with the decreased starch hydrolysis rate showed in the study. Moreover, FTIR results showed the existence of the interaction between KGM and starch. The morphological characterization demonstrated that the addition of KGM contributed to a more compact structure of freeze-dried wheat starch. And KGM inhibited the expansion of starch granules and formed a barrier around the gelatinized starch. Therefore, the barrier around the starch granules and the interaction between KGM and starch were considered to be the important reasons that affected the starch digestibility.

In-situ modified the surface of Pt-doped perovskite catalyst for soot oxidation.

In-situ modification is studied in this work on LaCo1-xPtxO3 for soot oxidation. A series of perovskite catalysts LaCo1-xPtxO3 (by sol-gel method) are modified with 30% H2O2. XRD, TEM, SEM, BET, XPS, Raman, in-situ DRIFTS, H2-TPR and TGA are used to investigate physicochemical properties of catalysts. TGA results show that all doped catalysts have a lower temperature of soot conversion, especially LaCo0.94Pt0.06O3 (T50 = 437 °C). The T50 of the catalyst with modification by H2O2 solution decreases at least 20 °C compared with the doped catalysts. A highly symmetrical structure and an obvious amorphous layer about 3-5 nm are observed in the modified catalysts. According to the XPS study, the symmetrical structure benefits to the movement of oxygen vacancy thus catalyst captures more adsorbed oxygen (about 95%). And the amorphous surface could adsorb more oxygen species. In addition, all catalysts show excellent aging resistance performance. The reaction mechanism of catalyst for soot oxidation is presented in the end.