Screening candidate diagnostic biomarkers for diabetic kidney disease.

BACKGROUND: There are big differences in treatments and prognosis between diabetic kidney disease (DKD) and non-diabetic renal disease (NDRD). However, DKD patients couldn't be diagnosed early due to lack of special biomarkers. Urine is an ideal non-invasive sample for screening DKD biomarkers. This study aims to explore DKD special biomarkers by urinary proteomics. MATERIALS AND METHODS: According to the result of renal biopsy, 142 type 2 diabetes mellitus (T2DM) patients were divided into 2 groups: DKD (n = 83) and NDRD (n = 59). Ten patients were selected from each group to define urinary protein profiles by label-free quantitative proteomics. The candidate proteins were further verifyied by parallel reaction monitoring (PRM) methods (n = 40). Proteins which perform the same trend both in PRM and proteomics were verified by enzyme-linked immunosorbent assays (ELISA) with expanding the sample size (n = 82). The area under the receiver operating characteristic curve (AUC) was used to evaluate the accuracy of diagnostic biomarkers. RESULTS: We identified 417 peptides in urinary proteins showing significant difference between DKD and NDRD. PRM verification identified C7, SERPINA4, IGHG1, SEMG2, PGLS, GGT1, CDH2, CDH1 was consistent with the proteomic results and p < 0.05. Three potential biomarkers for DKD, C7, SERPINA4, and gGT1, were verified by ELISA. The combinatied SERPINA4/Ucr and gGT1/Ucr (AUC = 0.758, p = 0.001) displayed higher diagnostic efficiency than C7/Ucr (AUC = 0.632, p = 0.048), SERPINA4/Ucr (AUC = 0.661, p = 0.032), and gGT1/Ucr (AUC = 0.661, p = 0.029) respectively. CONCLUSIONS: The combined index SERPINA4/Ucr and gGT1/Ucr can be considered as candidate biomarkers for diabetic nephropathy after adjusting by urine creatinine.

Comparative transcriptome analysis reveals the key genes and pathways involved in drought stress response of two wheat (Triticum aestivum L) varieties.

Drought stress results in significant yield losses in wheat production. Although studies have reported a number of wheat drought tolerance genes, a deeper understanding of the tolerance mechanisms is required for improving wheat tolerance against drought stress. In this study, we found that "Deguo 2" exhibited higher tolerance to drought than "Truman". Transcriptomics analysis enabled identification of 6084 and 7146 differentially expressed genes (DEGs), mainly mapping flavonoid biosynthesis, plant hormone, phenolamides and antioxidant pathways and revealed altered expression levels of about 700 genes. Exogenous melatonin application enhanced wheat tolerance against drought stress. Co-expression analysis showed that bHLH and bZIP transcription factors may be involved in the regulation of various pathway genes. Take together, these results provide new insights for us on exploring the crosstalk between phytohormones and secondary metabolites, and will deepen the understanding of the complex tolerance mechanisms against drought stress in wheat.

[Electrocardiogram signal classification based on fusion method of residual network and self-attention mechanism].

In the diagnosis of cardiovascular diseases, the analysis of electrocardiogram (ECG) signals has always played a crucial role. At present, how to effectively identify abnormal heart beats by algorithms is still a difficult task in the field of ECG signal analysis. Based on this, a classification model that automatically identifies abnormal heartbeats based on deep residual network (ResNet) and self-attention mechanism was proposed. Firstly, this paper designed an 18-layer convolutional neural network (CNN) based on the residual structure, which helped model fully extract the local features. Then, the bi-directional gated recurrent unit (BiGRU) was used to explore the temporal correlation for further obtaining the temporal features. Finally, the self-attention mechanism was built to weight important information and enhance model's ability to extract important features, which helped model achieve higher classification accuracy. In addition, in order to mitigate the interference on classification performance due to data imbalance, the study utilized multiple approaches for data augmentation. The experimental data in this study came from the arrhythmia database constructed by MIT and Beth Israel Hospital (MIT-BIH), and the final results showed that the proposed model achieved an overall accuracy of 98.33% on the original dataset and 99.12% on the optimized dataset, which demonstrated that the proposed model can achieve good performance in ECG signal classification, and possessed potential value for application to portable ECG detection devices.

High-speed two-dimensional terahertz spectroscopy with echelon-based shot-to-shot balanced detection.

By using a reflective-echelon-based electro-optic sampling technique and a fast detector, we develop a two-dimensional terahertz (THz) spectrometer capable of shot-to-shot balanced readout of THz waveforms at a full 1-kHz repetition rate. To demonstrate the capabilities of this new detection scheme for high-throughput applications, we use gas-phase acetonitrile as a model system to acquire two-dimensional THz rotational spectra. The results show a two-order-of-magnitude speedup in the acquisition of multidimensional THz spectra when compared to conventional delay-scan methods while maintaining accurate retrieval of the nonlinear THz signal. Our report presents a feasible solution for bringing the technique of multidimensional THz spectroscopy into widespread practice.

Establishing a Non-Invasive Gradeing Model for Primary IgA Nephropathy Based on Multi-Center Population.

BACKGROUND: It is necessary to adopt a special therapeutic schedule for treating IgA nephropathy (IgAN) at a distinct pathological stage. It would be helpful for treatment to know the pathological changes throughout the IgAN course; therefore, we want to establish a non-invasive method for determining the pathological grade of IgAN. METHODS: A total of 240 primary IgAN patients were recruited, and their clinical data and laboratory test results were collected. The study subjects were randomly divided into the training set (181 cases) and testing set (59 cases). The ordered logistic regression model was constructed with variables which were selected by single-factor and multi-factor stepwise regression analysis in training set, then the model was verified by testing set. RESULTS: Logistic regression analysis showed that hematuria, hemoglobin, urea, complement 3, urinary microalbumin and urinary microalbumin/creatinine are related to Lee's classification of IgAN. Using the above indicators as independent variables to establish the non-invasive grading model. The model's accuracy is as high as 82.9% (p = 0.00), and the rate of precision, recall, and specificity for each group are all above 80%. This model discriminates four classes of pathological stage corresponding to Lee's grading well. CONCLUSIONS: A non-invasive grading model for primary IgAN has been established successfully by clinical and laboratory data.

Dual-beam intracavity optical tweezers with all-optical independent axial and radial self-feedback control schemes.

The feedback control to optical tweezers is an obvious approach to improve the optical confinement. However, the electronic-based feedback controlling system in optical tweezers usually consists of complex software and hardware, and its performance is limited by the inevitable noise and time-delay from detecting and controlling devices. Here, we present and demonstrate the dual-beam intracavity optical tweezers enabling all-optical independent radial and axial self-feedback control of the trapped particle's radial and axial motions. We have achieved the highest optical confinement per unit intensity to date, to the best of our knowledge. Moreover, both the axial and radial confinements are adjustable in real-time, through tuning the foci offset of the clockwise and counter-clockwise beams. As a result, we realized three-dimensional self-feedback control of the trapped particle's motions with an equivalent level in the experiment. The dual-beam intracavity optical tweezers will significantly expand the range of optical manipulation in further studies of biology, physics and precise measurement, especially for the sample that is extremely sensitive to heat.

Self-feedback induced bistability in dual-beam intracavity optical tweezers.

The intracavity optical tweezers is a new, to the best of our knowledge, cavity optomechanics system, implementing a self-feedback control of the particle's position by trapping the particle inside an active ring cavity. This self-feedback mechanism efficiently constructs a novel potential in the cavity. Here we predict and give experimental evidence for the self-feedback induced optical bistability in dual-beam intracavity optical tweezers. Then the characteristics of these bistable potential wells are investigated. The results show that we can prevent the bistable behaviors from destabilizing the trapping stability through tuning the foci offset of two propagating beams in the cavity. This contributes to the use of intracavity optical tweezers as a powerful tool for optical manipulation. Importantly, the thermally activated transition of the trapped particle in the bistable potential is observed for particular experimental parameters. Further investigation of this phenomenon could underlie the mechanism of many metastable-related processes in physics, chemistry, and biology.

Ethnic disparities in stillbirth risk in Yunnan, China: a prospective cohort study, 2010-2018.

BACKGROUND: Racial and ethnic disparities in stillbirth risk had been documented in most western countries, but it remains unknown in China. This study was to determine whether exist ethnic disparities in stillbirth risk in mainland China. METHODS: Pregnancy outcomes and ethnicity data were obtained from the National Free Preconception Health Examination Project (NEPHEP), a nationwide prospective population-based cohort study conducted in Yunnan China from 2010-2018. The Han majority and other four main minorities including Yi, Dai, Miao, Hani were investigated in the analysis. The stillbirth hazards were estimated by life-table analysis. The excess stillbirth risk (ESR) was computed for Chinese minorities using multivariable logistic regression. RESULTS: Compared with other four minorities, women in Han majority were more likely to more educated, less multiparous, and less occupied in agriculture. The pattern of stillbirth hazard of Dai women across different gestation intervals were found to be different from other ethnic groups, especially in 20-23 weeks with 3.2 times higher than Han women. The ESR of the Dai, Hani, Miao, and Yi were 45.05, 18.70, -4.17 and 12.28%, respectively. Adjusted for maternal age, education, birth order and other general risk factors, the ethnic disparity still persisted between Dai women and Han women. Adjusted for preterm birth further (gestation age <37 weeks) can reduce 16.91% ESR of Dai women and made the disparity insignificant. Maternal diseases and congenital anomalies explained little for ethnic disparities. CONCLUSIONS: We identified the ethnic disparity in stillbirth risk between Dai women and Han women. General risk factors including sociodemographic factors and maternal diseases explained little. Considerable ethnic disparities can be attributed to preterm birth.

Optical confinement efficiency in the single beam intracavity optical tweezers.

Single beam intracavity optical tweezers characterizes a novel optical trapping scheme where the laser operation is nonlinearly coupled to the motion of the trapped particle. Here, we first present and establish a physical model from a completely new perspective to describe this coupling mechanism, using transfer matrices to calculate the loss of the free-space optical path and then extracting the scattering loss that caused by the 3D motions of the particle. Based on this model, we discuss the equilibrium position in the single beam intracavity optical tweezers. The influences of the numerical aperture, pumping power, particle radius and refractive index on the optical confinement efficiency are fully investigated, compared with standard optical tweezers. Our work is highly relevant for guiding the experiments on the single beam intracavity optical tweezers to achieve higher optical confinement efficiency.

Ruthenium-Catalyzed Selectively Oxidative C-H Alkenylation of N-Acylated Aryl Sulfonamides by Using Molecular Oxygen as an Oxidant.

A ruthenium-catalyzed sulfonamide-directed ortho aryl C-H alkenylation/annulation to afford five-membered sultam by using of molecular oxygen as an oxidant is reported in this article. Compared to the previous transition-metal-catalyzed C-H alkenylation of aryl sulfonamides, no excess metal salt oxidant was required in this method. A wide sulfonamide substrates scope and good regioselectivity and site-selectivity make this Ru-catalyzed method more attractive. Importantly, this method can not only be used to effectively prepare the biologically active five-membered sultam molecules but also be efficiently applied to the late-stage modification of sulfonamide drugs.

Distinguishing Four HCV Genotypes by Loop Mediated Isothermal Amplification Assay.

BACKGROUND: Genotyping of hepatitis C virus (HCV) is of great significance for clinical diagnosis and treatment. The object of this work was to establish a loop-mediated isothermal amplification (LAMP) method for four subtypes of HCV prevalent in China. METHODS: Gene sequences of HCV-1b, 2a, 3, and 6a were downloaded from Genebank. Primer sets of the four HCV subtypes for LAMP method were designed by Primer Explorer V.4. LAMP reactions were performed at 65°C for 60 minutes. Sera of HCV-1b, 2a, 3, and 6a, HBV-A, HBV-B, HIV-1, HIV-2 and HAV, synthesized nucleic acid of HCV-4a, and 5a were used for evaluation of LAMP performance. For specificity evaluation, each primer set for HCV-1b, 2a, 3, and 6a was tested with all kinds of sera. Each serum of the above 4 HCV subtypes was diluted and aliquoted into 10 parts. RNA was subsequently extracted, which was detected by LAMP and Real-time PCR to verify limit of detection (LOD). RESULTS: The LAMP assay established in this study could detect and distinguish HCV-1b, 2a, 3, and 6a. Consistent with gene sequencing methods, specificity of HCV-1b, 2a, 3, and 6a was 100%, 85%, 90%, and 100% detected by LAMP, respectively. The LOD of HCV-1b, 3, and 6a was 1.5 x 103 IU/mL. The LOD of HCV2a was 1.0 x 103 IU/mL with the LAMP method. CONCLUSIONS: The LAMP method established in this study is feasible for distinguishing HCV-1b, 2a, 3, and 6a specifically and sensitively.

Modified calanolides incorporated with furan-2-nitro mimics against Mycobacterium tuberculosis.

(+)-Calanolide A was identified as an active agent against both HIV-1 and Mycobacterium tuberculosis (Mtb). We modified Ring D of calanolide compounds with furan-2-nitro mimics and obtained 15 compounds. After in vitro tests, two compounds were shown to be active against replicating (R) Mtb, but not against non-replicating (NR) Mtb. Further optimization for potent candidates against both R Mtb and NR Mtb will result from this research.

Construction of rod-like cobalt-pyridinedicarboxylic acid/MXene nanosheets composites for hydrogen evolution reaction and supercapacitor.

Metal-organic frameworks (MOFs) have attracted considerable attention in the field of energy storage and conversion due to their large specific surface area, regulatable pore structure and composition. However, the poor electrical conductivity and few active sites of MOFs impede their application. Herein, highly conductive MXene nanosheets are introduced to modulate the electronic conductivity and structure of rod-like Co-pyridinedicarboxylic acid (Co-PDC), and thus enhancing the electrochemical performance of MOFs. The heterostructural Co-PDC/MXene (CPM) was facily synthesized at room temperature. The as-prepared CPM-30 with 30 % MXene only requires the overpotential of 75.1 mV to achieve a current density of 10 mA cm-2 for hydrogen evolution reaction (HER), and the assembled electrolytic cell with CPM-30 and RuO2 as cathode and anode electrodes can achieve a current density of 10 mA cm-2 at a voltage of 1.65 V. In addition, CPM-10 exhibits a high specific capacitance of 583.1 F g-1 at 0.5 A g-1 and an excellent rate performance of 41.6 % at 50 A g-1. Furthermore, the assembled asymmetric supercapacitor CPM-10//AC exhibited an energy density of 15.55 Wh kg-1 at a power density of 750 W kg-1 and excellent stability with a capacitance retention rate of 95 % after 10,000 cycles. The excellent electrochemical properties of Co-PDC/MXene are attributed to the unique structure and synergistic effect of Co-PDC and MXene.

The analysis of inducible family members in the water flea Daphnia magna led to the identification of an uncharacterized lineage of heat shock protein 70.

To explore the function and evolutionary relationships of inducible heat shock protein 70 (Hsp70) in Daphnia magna, cDNAs of four Hsp70 family members (DmaHsp70, DmaHsp70-2, DmaHsp70-12, DmaHsp70-14) were cloned. While all DmaHsp70s possess three function domains, it is noteworthy that only DmaHsp70 ends with a "EEVD" motif. Phylogenetic analysis indicates that the Hsp70-12 lineage is distanced from the rest, and therefore it is an uncharacterized lineage of Hsp70. The differences in isoelectric point and 3-dimensional (3D) conformation of the N-terminal nucleotide binding domain (NBD) of DmaHsp70s further support the theory. DmaHsp70s exhibit varied motif distribution patterns and the logo sequences of motifs have diverse signature characteristics, indicating that different mechanisms are involved in the regulation of ATP binding and hydrolysis for the DmaHsp70s. Protein-protein network together with the predicted subcellular locations of DmaHsp70s suggest that they likely fulfill distinct roles in cells. The transcription of four DmaHsp70s were changed during the recovery stage after thermal stress or oxidative stress. But the expression pattern of them were dissimilar. Collectively, these results collectively elucidated the identification of a previously uncharacterizedHsp70 lineage in animal and extended our understanding of the Hsp70 family.

Blocking lncRNA HCG18 re-sensitizes Taxol resistant lung cancer cells to Taxol through modulating the miR-34a-5p/HDAC1 axis.

Lung cancer is one of the most frequently diagnosed cancers worldwide, associated with a poor survival rate. Taxol (Paclitaxel) is commonly used as a chemotherapeutic treatment for advanced lung cancers. While Taxol has improved clinical outcomes for lung cancer patients, a significant number of them develop resistance to Taxol, resulting in treatment failure. The role of the long noncoding RNA HCG18 in lung cancer and Taxol resistance has not yet been fully understood. To investigate this, we examined the expression of HCG18 and miR-34a-5p in lung tumors and normal lung tissues using qRT-PCR. We also assessed Taxol resistance through cell viability and apoptosis assays. Through the starBase online service, we analyzed the interactions between lncRNA and mRNA as well as miRNA and mRNA. We further validated the association between lncRNA and miRNA through luciferase and RNA pull-down assays. Our findings demonstrated that HCG18 was significantly upregulated in lung cancer tissues compared to normal lung tissues. Silencing HCG18 increased the sensitivity of lung cancer cells to Taxol. Additionally, our study established a Taxol-resistant cell line and observed a substantial upregulation of HCG18 in Taxol-resistant lung cancer cells. Bioinformatic analysis predicted that HCG18 could bind to miR-34a-5p, forming a competing endogenous RNA network, which was confirmed through luciferase assay. We found that miR-34a-5p was downregulated in lung cancer tissues and negatively correlated with Taxol resistance, as it directly bound to the 3'UTR region of HDAC1. Further results showed that inhibition of HCG18 significantly increased miR-34a-5p expression and sensitized lung cancer cells to Taxol. This sensitization could be reversed by inhibiting miR-34a-5p. Finally, we demonstrated in a xenograft mouse model that inhibition of HCG18 sensitized Taxol-resistant lung cancer cells to Taxol treatment by modulating the miR-34a-5p-HDAC1 axis. In conclusion, our in vitro and in vivo results uncover a novel molecular mechanism by which HCG18 promotes Taxol resistance through modulation of the miR-34a-5p/HDAC1 axis. These findings contribute to the diagnosis and treatment of chemo-resistant lung cancer.

MAUNext: a lightweight segmentation network for medical images.

Objective. The primary objective of this study is to enhance medical image segmentation techniques for clinical research by prioritizing accuracy and the number of parameters.Approach. To achieve this objective, a novel codec-based MAUNext approach is devised, focusing on lightweight backbone design and the integration of skip connections utilizing multiscale, attention mechanism, and other strategic components. The approach is composed of three core modules: a multi-scale attentional convolution module for improved accuracy and parameter reduction, a collaborative neighbourhood-attention MLP encoding module to enhance segmentation performance, and a tiny skip-connected cross-layer semantic fusion module to bridge the semantic gap between encoder and decoder.Main results. The study extensively evaluates the MAUNext approach alongside eight state-of-the-art methods on three renowned datasets: Kagglelung, ISIC, and Brain. The experimental outcomes robustly demonstrate that the proposed approach surpasses other methods in terms of both parameter numbers and accuracy. This achievement holds promise for effectively addressing medical image segmentation tasks.Significance. Automated medical image segmentation, particularly in organ and lesion identification, plays a pivotal role in clinical diagnosis and treatment. Manual segmentation is resource-intensive, thus automated methods are highly valuable. The study underscores the clinical significance of automated segmentation by providing an advanced solution through the innovative MAUNext approach. This approach offers substantial improvements in accuracy and efficiency, which can significantly aid clinical decision-making and patient treatment.

The Landscape of m6A Regulators in Multiple Brain Regions of Alzheimer's Disease.

Alzheimer's disease research has been conducted for many years, yet no effective cure methods have been found. N6-methyladenosine (m6A) RNA methylation, an essential post-transcriptional regulation mechanism, has been discovered to affect essential neurobiological processes, such as brain cell development and aging, which are closely related to neurodegenerative diseases such as Alzheimer's disease. The relationship between Alzheimer's disease and the m6A mechanism still needs further investigation. Our work evaluated the alteration profile of m6A regulators and their influences on Alzheimer's disease in 4 brain regions: the postcentral gyrus, superior frontal gyrus, hippocampus, and entorhinal cortex. We found that the expression levels of the m6A regulators FTO, ELAVL1, and YTHDF2 were altered in Alzheimer's disease and were related to pathological development and cognitive levels. We also assessed AD-related biological processes influenced by m6A regulators via GSEA and GSVA method. Biological Processes Gene Ontology terms including memory, cognition, and synapse-signaling were found to potentially be affected by m6A regulators in AD. We also found different m6A modification patterns in AD samples among different brain regions, mainly due to differences in m6A readers. Finally, we further evaluated the importance of AD-related regulators based on the WGCNA method, assessed their potential targets based on correlation relationships, and constructed diagnostic models in 3 of all 4 regions using hub regulators, including FTO, YTHDC1, YTHDC2, etc., and their potential targets. This work aims to provide a reference for the follow-up study of m6A and Alzheimer's disease.

Insertion of a totally implantable vascular access device in a patient with dextrocardia and colon cancer: a case report.

Colon cancer in patients with situs inversus totalis is rarely associated with dextrocardia, and chemotherapy is commonly used for treatment. Central venous access devices are used to administer intravenous fluids and chemotherapy in patients with colon cancer. Compared with peripherally inserted central catheters and Hickman-type tunneled catheters, totally implantable vascular access devices (TIVADs) are safer and more effective. However, positioning the catheter tip may be challenging in patients with dextrocardia and situs inversus. We herein describe a novel case involving a patient with dextrocardia and colon cancer who was treated by TIVAD insertion with intracavitary electrocardiography-aided tip localization.

Microglia-Mediated Neurovascular Unit Dysfunction in Alzheimer's Disease.

The neurovascular unit (NVU) is involved in the pathological changes in Alzheimer's disease (AD). The NVU is a structural and functional complex that maintains microenvironmental homeostasis and metabolic balance in the central nervous system. As one of the most important components of the NVU, microglia not only induce blood-brain barrier breakdown by promoting neuroinflammation, the infiltration of peripheral white blood cells and oxidative stress but also mediate neurovascular uncoupling by inducing mitochondrial dysfunction in neurons, abnormal contraction of cerebral vessels, and pericyte loss in AD. In addition, microglia-mediated dysfunction of cellular components in the NVU, such as astrocytes and pericytes, can destroy the integrity of the NVU and lead to NVU impairment. Therefore, we review the mechanisms of microglia-mediated NVU dysfunction in AD. Furthermore, existing therapeutic advancements aimed at restoring the function of microglia and the NVU in AD are discussed. Finally, we predict the role of pericytes in microglia-mediated NVU dysfunction in AD is the hotspot in the future.