Structural basis of bacterial σ28 -mediated transcription reveals roles of the RNA polymerase zinc-binding domain.

In bacteria, σ28 is the flagella-specific sigma factor that targets RNA polymerase (RNAP) to control the expression of flagella-related genes involving bacterial motility and chemotaxis. However, the structural mechanism of σ28 -dependent promoter recognition remains uncharacterized. Here, we report cryo-EM structures of E. coli σ28 -dependent transcribing complexes on a complete flagella-specific promoter. These structures reveal how σ28 -RNAP recognizes promoter DNA through strong interactions with the -10 element, but weak contacts with the -35 element, to initiate transcription. In addition, we observed a distinct architecture in which the ß' zinc-binding domain (ZBD) of RNAP stretches out from its canonical position to interact with the upstream non-template strand. Further in vitro and in vivo assays demonstrate that this interaction has the overall effect of facilitating closed-to-open isomerization of the RNAP-promoter complex by compensating for the weak interaction between σ4 and -35 element. This suggests that ZBD relocation may be a general mechanism employed by σ70 family factors to enhance transcription from promoters with weak σ4/-35 element interactions.

Cholangiocarcinoma presenting as dysphagia and misdiagnosed as gastritis: a case report.

BACKGROUND: Heterotopic tumor is a rare disease. Thus far, no cases of heterotopic cholangiocarcinoma have been reported in the world. Cholangiocarcinoma mainly metastasizes by direct invasion, and it can lead to liver metastasis in its advanced stage. There were few clinical cases of gastric metastasis in advanced tumors, mainly seen in breast cancer, lung cancer, liver cancer, malignant melanoma, choriocarcinoma, and hematological tumors. Metastases of cholangiocarcinoma to the stomach also are exceptionally rare. CASE PRESENTATION: A 58-year-old man was admitted to the hospital because of difficulty swallowing for one year. Upon gastroscopy, we found the tumor at the region of the cardia and gastric fundus. Macroscopical appearance of the tumor suggested its malignant nature. Computed tomography (CT) findings showed that the wall of the cardia, fundus, and stomach body were thickened, suggesting a tumor. Because the patient had obvious difficulty swallowing, we invited cardiothoracic surgeons for consultation. They considered that the patient had definite mechanical obstruction in the lower esophagus; hence, they performed an operation. Immunohistochemical staining revealed low-to-medium differentiated adenocarcinoma (containing mucinous adenocarcinoma components) of biliary origin. CONCLUSIONS: We highlight the importance of the endoscopic biopsy of gastric tumor. However, when its results are inconsistent with the clinician's judgment, further examination is required. Endoscopic ultrasonography and enhanced CT may be a good choice. If necessary, on the premise of patient acceptance, the diagnosis could be confirmed after surgical excision. Here we report a case of a patient with heterotopic cholangiocarcinoma in the gastric fundus. The most common tissue ectopias in the digestive tract include esophagogastric gastric mucosal ectopia, duodenal gastric mucosal ectopia, and gastric mucosal small intestinal ectopia. Thus far, there have been no reports of ectopic cholangiocarcinoma and associated cancer in the stomach. In addition, metastases of cholangiocarcinoma to the stomach are also exceptionally rare, and most of them are due to a direct invasion. The discovery of the primary lesion is an important clue for the reliable diagnosis in such cases.

Metal oxide-based macroporous ordered double affinity molecularly imprinted polymer for specific separation and enrichment of glycoprotein from food samples: a co-modification of DMSA and boronate affinity.

Metal oxide-based macroporous ordered double affinity molecularly imprinted polymers (D-MIPs) were developed as solid phase extraction (SPE) adsorbents for the specific identification of ovalbumin (OVA) under physiological pH conditions prior to ultraviolet visible (UV-vis) spectrophotometric detection. Herein, macroporous alumina (MA) was used as a matrix; dimercaptosuccinic acid (DMSA) and 3-aminophenylboric acid (APBA) were employed as dual-functional monomers; APBA is a self-polymerizing monomer. The effects of synthesis conditions, SPE conditions as well as selectivity, reproducibility, and reusability were studied. The co-modification of DMSA and boronate affinity renders the adsorbent exhibiting a high adsorption capacity (114.4 mg g-1) and short equilibrium time (30 min). The surface imprinting technology causes the adsorbent to have high selectivity towards OVA. The OVA recovery range is 91.1-99.6%. This study provides a promising method for the enrichment of OVA and other cis-diol-containing analytes in complex biological samples. A novel metal oxide-based macroporous ordered nanoparticle with a combination of DMSA and boronate affinity was successfully prepared for specific separation and enrichment of glycoprotein from complex biological samples.

Medicine-Food Herbs against Alzheimer's Disease: A Review of Their Traditional Functional Features, Substance Basis, Clinical Practices and Mechanisms of Action.

Alzheimer's disease (AD) is a progressive, neurodegenerative disorder that currently has reached epidemic proportions among elderly populations around the world. In China, available traditional Chinese medicines (TCMs) that organically combine functional foods with medicinal values are named "Medicine Food Homology (MFH)". In this review, we focused on MFH varieties for their traditional functional features, substance bases, clinical uses, and mechanisms of action (MOAs) for AD prevention and treatment. We consider the antiAD active constituents from MFH species, their effects on in vitro/in vivo AD models, and their drug targets and signal pathways by summing up the literature via a systematic electronic search (SciFinder, PubMed, and Web of Science). In this paper, several MFH plant sources are discussed in detail from in vitro/in vivo models and methods, to MOAs. We found that most of the MFH varieties exert neuroprotective effects and ameliorate cognitive impairments by inhibiting neuropathological signs (Aß-induced toxicity, amyloid precursor protein, and phosphorylated Tau immunoreactivity), including anti-inflammation, antioxidative stress, antiautophagy, and antiapoptosis, etc. Indeed, some MFH substances and their related phytochemicals have a broad spectrum of activities, so they are superior to simple single-target drugs in treating chronic diseases. This review can provide significant guidance for people's healthy lifestyles and drug development for AD prevention and treatment.

Facile PEG-based isolation and classification of cancer extracellular vesicles and particles with label-free surface-enhanced Raman scattering and pattern recognition algorithm.

Extracellular vesicles and particles (EVPs), which contain the same surface proteins as their mother cells, are promising biomarkers for cancer liquid biopsy. However, most of the isolation methods of EVPs are time-consuming and complicated, and hence, sensitive detection and classification methods are required for EVPs. Here, we report a facile polyethylene glycol (PEG)-based method for isolating and classifying EVPs with label-free surface-enhanced Raman scattering (SERS) and pattern recognition algorithm. There are only three steps in the PEG-based isolation method, and it does not require ultracentrifugation, which makes it a low-cost and easy-to-use method. Three types of common male cancer cell lines, namely leukemia (THP-1), prostate cancer (DU-145), and colorectal cancer (COLO-205), and one healthy male blood sample, were utilized to isolate EVPs. To collect the SERS spectra of EVPs, a novel planar nanomaterial, namely amino molybdenum oxide (AMO) nanoflakes, was applied, with the enhancement factor being obtained as 3.2 × 102. Based on the principal component analysis and support vector machine (PCA-SVM) algorithm, cancer and normal EVPs were classified with 97.4% accuracy. However, among the cancer EVPs, the accuracy, precision, and sensitivity were found to be 90.0%, 90.9%, and 83.3% for THP-1; 86.7%, 80.0%, and 92.3% for DU-145; 96.7%, 83.3%, and 100% for COLO-205, respectively. Thus, this work will improve the isolation, detection, and classification of EVPs and promote the development of cancer liquid biopsies.

A compact fiber-integrated optofluidic platform for highly specific microRNA Förster resonance energy transfer detection.

MicroRNAs (miRNAs) have attracted extensive interest as promising biomarkers for the profiling of diseases. However, quantitative measurement of miRNAs presents a significant challenge in biochemical studies. In this work, we developed an innovative optofluidic platform to perform a rapid, simple, quantitative and high-specificity miRNA assay using the Förster resonance energy transfer (FRET) principle. A novel three-way junction FRET probe was proposed to enable rapid and enzyme-free miRNA detection. Using this platform, we performed one-step, amplification-free miRNA detection with simple device operation and achieved miRNA identification at a low concentration. The detection system could achieve high specificity for discrimination of three-base mismatches, and the sample volume was significantly reduced, favorable for low-level miRNA detection in material-limited samples. The establishment of a compact, low-cost, highly sensitive and selective miRNA analysis platform provides a valuable tool for point-of-care diagnosis.

Exploration of SARS-CoV-2 3CLpro Inhibitors by Virtual Screening Methods, FRET Detection, and CPE Assay.

COVID-19 caused by a novel coronavirus (SARS-CoV-2) has been spreading all over the world since the end of 2019, and no specific drug has been developed yet. 3C-like protease (3CLpro) acts as an important part of the replication of novel coronavirus and is a promising target for the development of anticoronavirus drugs. In this paper, eight machine learning models were constructed using naïve Bayesian (NB) and recursive partitioning (RP) algorithms for 3CLpro on the basis of optimized two-dimensional (2D) molecular descriptors (MDs) combined with ECFP_4, ECFP_6, and MACCS molecular fingerprints. The optimal models were selected according to the results of 5-fold cross verification, test set verification, and external test set verification. A total of 5766 natural compounds from the internal natural product database were predicted, among which 369 chemical components were predicted to be active compounds by the optimal models and the EstPGood values were more than 0.6, as predicted by the NB (MD + ECFP_6) model. Through ADMET analysis, 31 compounds were selected for further biological activity determination by the fluorescence resonance energy transfer (FRET) method and cytopathic effect (CPE) detection. The results indicated that (+)-shikonin, shikonin, scutellarein, and 5,3',4'-trihydroxyflavone showed certain activity in inhibiting SARS-CoV-2 3CLpro with the half-maximal inhibitory concentration (IC50) values ranging from 4.38 to 87.76 µM. In the CPE assay, 5,3',4'-trihydroxyflavone showed a certain antiviral effect with an IC50 value of 8.22 µM. The binding mechanism of 5,3',4'-trihydroxyflavone with SARS-CoV-2 3CLpro was further revealed through CDOCKER analysis. In this study, 3CLpro prediction models were constructed based on machine learning algorithms for the prediction of active compounds, and the activity of potential inhibitors was determined by the FRET method and CPE assay, which provide important information for further discovery and development of antinovel coronavirus drugs.

DL0410 ameliorates cognitive disorder in SAMP8 mice by promoting mitochondrial dynamics and the NMDAR-CREB-BDNF pathway.

Alzheimer's disease (AD) is a worldwide problem and there are no effective drugs for AD treatment. Previous studies show that DL0410 is a multi-target, anti-AD agent. In this study, we investigated the therapeutic effect of DL0410 and its action mechanism in SAMP8 mice. DL0410 (1-10 mg·kg-1·d-1) was orally administered to 8-month-old SAMP mice (SAMP8) for 8 weeks. We showed that DL0410 administration effectively ameliorated the cognitive deficits in the Morris water maze test, novel object recognition test, and nest building test. We revealed that DL0410 dose-dependently increased the expression levels of the mitochondrial proteins (PGC-1α, Mitofusin 2, OPA1, and Drp1), and subsequently ameliorated the processes of mitochondrial biosynthesis, fusion, and fission in the cortex and hippocampus of SAMP8 mice. Furthermore, DL0410 administration promoted the expression of synaptic proteins (synaptophysin and PSD95) in the brain of SAMP8 mice, and upregulated the protein phosphorylation in NMDAR-CAMKII/CAMKIV-CREB pathway responsible for the synaptic plasticity. DL0410 administration dose-dependently increased the expression of BDNF and TrkB, and the neurotrophic effect was mediated via the ERK1/2 and PI3K-AKT-GSK-3ß pathways. DL0410 administration upregulated Bcl-2, increased the Bcl-2/Bax ratio and the level of caspase 3 and PARP-1, alleviating neuronal apoptosis. We proposed that the NMDAR-CREB-BDNF pathway might establish a positive feedback loop between synaptic plasticity and neurotrophy, with CREB at the center. In summary, DL0410 promotes synaptic function and neuronal survival, thus ameliorating cognitive deficits in SAMP8 mice via improved mitochondrial dynamics and increased activity of the NMDAR-CREB-BDNF pathway. DL0410 is a promising candidate to treat aging-related AD, and deserves more research and development in future.

Multiplex immunohistochemistry indicates biomarkers in colorectal cancer.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females, whose survival ratio and indicating biomarkers are limited. The rapid development of multiple immunofluorescences gives rise to widespread applications of this new advanced technology called multiplex immunohistochemistry (mIHC), which makes it possible to detect several fluorescent proteins on the same tumor tissue microarray (TMA) within the same time and spatial organization. By taking advantage of this mIHC technology, we detected three tumor-associated antigens (TAA) including the human epidermal growth factor receptor 2 (HER2), the cluster of differentiation 133 (CD133), the programmed death ligand-1 (PD-L1), and one immune-associated macrophage marker, the cluster of differentiation 68 (CD68) in cancer tissues versus para-carcinomatous normal tissues derived from a cohort of 84 CRC patients. All four markers were upregulated in cancer tissue compared with normal tissues. And the expressions of CD133, HER2, PD-L1, and CD68 were correlated with pathological grade, T stage, tumor size, metastasis, respectively. Accordingly, CD133 and PD-L1 could be applied as potential diagnostic biomarkers for CRC at an early stage, while the enrichment of HER2 might act as an advanced indicator in aggressive cancer status of CRC; whereas, CD68 could be potentially considered as an advanced diagnostic indicator in CRC patients, as well as a metastatic promoter in CRC-related TME. The differential expression of these four proteins, as well as their clinicopathological correlation, indicates that these four proteins could be utilized as specific diagnostic and prognostic biomarkers in CRC patients.

ZIF-based boronic acid functionalized metal-organic frameworks for the enrichment of cis-diol-containing luteolin from food samples prior to HPLC.

Zeolite imidazole framework-based boronic acid-functionalized metal-organic frameworks (ZIF-67@PDA@BA-Zr-MOFs) were developed as an adsorbent for solid phase extraction (SPE) of luteolin (LTL) from peanut shell samples. Herein, ZIF-67 as a support matrix, polydopamine (PDA) as a coating to introduce amino and hydroxyl groups on the matrix surface to fix metal-organic frameworks (MOFs), zirconium tetrachloride (ZrCl4) as a precursor, terephthalic acid (TPA), and 3-carboxyphenylboronic acid (3-CPBA) as the mutual organic building blocks, and 3-CPBA was also a boronate affinity functional monomer. The effects of synthesis conditions, SPE conditions, selectivity, competitivity, reproducibility, and reusability were evaluated in detail. Under the optimal conditions, the maximum adsorption capacity is 71.4 mg g-1. The utility of ZIF-67@PDA@BA-Zr-MOFs as an adsorbent for SPE of LTL is supported by the presence of the abundant pore structure, as well as the boronate affinity sites facilitated the rapid binding of the adsorbent to the template. The concentration of the extracted LTL was determined by the high-performance liquid chromatography-ultraviolet (HPLC-UV), with calibration plots being linear in the concentration range 0.05-100 mg L-1 and a limit of detection (LOD) of 0.035 mg L-1. The method was applied to determine the LTL in peanut shell samples and recovered the target analyte in the range 85.6% to 99.2% (the standard deviations are less than 3.3%, n = 3). In addition, we incorporated boronate affinity and MOFs material into an SPE system to provide a promising strategy to detect other cis-diol-containing analytes in the complex matrix.

Factors affecting in-hospital cost and mortality of patients with stroke: Evidence from a case study in a tertiary hospital in China.

OBJECTIVE: The study aims to investigate the factors causing the difference of stroke patients' in-hospital cost and study these factors on health outcome in terms of mortality. METHODS: Eight hundred and sixty-two in-patients with stroke in a tertiary hospital in China from 2017 to 2019 were included in the database. Descriptive statistics indexes were used to describe patients' in-hospital cost and mortality. Based on Elixhauser coding algorithms, multiple linear regression and logistic regressions (LRs) were used to evaluate the impact of factors identified from univariate analysis on in-hospital cost and mortality, respectively. In addition to LRs, a comparison study was then carried out with random forest, gradient boosting decision tree and artificial neural network. RESULTS: Factors affecting both cost and mortality are age, discharged day-of-week, length of stay, stroke subtype, other neurological disorders, renal failure, fluid and electrolyte disorders and total number of comorbidities. CONCLUSION: With the increase of age, the mortality rate of in-patients (except for the juvenile) with stroke increases and the cost of hospitalization decreases. Intracerebral haemorrhage is the most devastating stroke for its highest mortality in short length of stay. Medical services should focus on these specific comorbidities.

Improving single-cell transcriptome sequencing efficiency with a microfluidic phase-switch device.

In this paper, we present a novel method to improve the efficiency of single-cell transcriptome sequencing for analyzing valuable cell samples. The microfluidic device we designed integrates multiple single-cell isolation chambers with hydrodynamic traps and achieves a nearly 100% single-cell capture rate and minimal cell loss, making it particularly suitable for samples with limited numbers of cells. Single cells were encapsulated using a novel phase-switch method into picoliter-sized hydrogel droplets and easily recovered for subsequent reactions. Minimizing the reaction volume resulted in a high reverse transcription (RT) efficiency for RNA sequencing (RNA-Seq). With this novel microfluidic platform, we captured dozens of hESCs (H9) simultaneously and obtained live cells in individual picoliter volumes, thus allowing for the convenient construction of a high-quality library for deep single-cell RNA-Seq. Our single-cell RNA-Seq results confirmed that a spectrum of pluripotency existed within an H9 colony. This integrated microfluidic platform can be applied to various cell types for the investigation of rare cellular events, and the phase-switch single-cell processing strategy will improve the efficiency and accessibility of single-cell transcriptome sequencing analysis.

Synergistic effects of Pb and repeated heat pulse on developmental neurotoxicity in zebrafish.

Pollutant discharges to the aquatic environment often contain multiple environmental stressors, affecting aquatic organisms. To mimic the discharges from nuclear and industry facilities, the combined effects of two independent types of stressors, heavy metal Pb and repeated heat pulse were addressed in this study. We investigated the developmental toxicity of combined treatment, especially its toxic effects on zebrafish neurodevelopment. The normal embryos at 4 hpf were exposed to 0.2 mM of Pb dissolved in the bathing medium with different temperatures (30, 32, and 34 °C) and then maintained in an incubator at 28 °C. After performing above treatment once every 24 h for 6 days, we found that combined treatment significantly affected neural development, including loss of dopaminergic (DA) neurons and brain vasculature, disruption of locomotor activity and neurodevelopmental genes expression in a temperature-dependent manner as compared to the Pb alone exposure group, indicating that repeated heat pulse enhances these negative impacts induced by Pb. In contrast, no apparent toxicity was observed in repeated heat pulse alone groups, suggesting that Pb treatment reduces thermal tolerance in zebrafish, which emphasized the importance to evaluate synergistic effects of Pb and repeated heat pulse. Moreover, repeated heat pulse aggravated Pb-induced apoptosis in the zebrafish brain. Further study of the underlying mechanism suggested that Caspase 3 regulated apoptosis was involved in this process. Taken together, our findings shed light on the full understanding of toxic effects of discharges from industrial applications on living organisms and its environmental impact.

Remarkable water-mediated proton conductivity of two porous zirconium(IV)/hafnium(IV) metal-organic frameworks bearing porphyrinlcarboxylate ligands.

Obtaining crystalline materials with high structural stability as well as super proton conductivity is a challenging task in the field of energy and material chemistry. Therefore, two highly stable metal-organic frameworks (MOFs) with macro-ring structures and carboxylate groups, Zr-TCPP (1) and Hf-TCPP (2) assembled from low-toxicity as well as highly coordination-capable Zr(IV)/Hf(IV) cations and the multifunctional linkage, meso-tetra(4-carboxyphenyl)porphine (TCPP) have attracted our strong interest. Note that TCPP as a large-size rigid ligand with high symmetry and multiple coordination sites contributes to the formation of the two stable MOFs. Moreover, the pores with large sizes in the two MOFs favor the entry of more guest water molecules and thus result in high H2O-assisted proton conductivity. First, their distinguished structural stabilities covering water, thermal and chemical stabilities were verified by various determination approaches. Second, the dependence of the proton conductivity of the two MOFs on temperature and relative humidity (RH) is explored in depth. Impressively, MOFs 1 and 2 demonstrated the optimal proton conductivities of 4.5 × 10-4 and 0.78 × 10-3 S·cm-1 at 100 °C/98 % RH, respectively. Logically, based on the structural information, gas adsorption/desorption features, and activation energy values, their proton conduction mechanism was deduced and highlighted.

Flubendazole suppresses VEGF-induced angiogenesis in HUVECs and exerts antitumor effects in PC-3 cells.

Flubendazole, an FDA-approved anthelmintic, has been predicted to show strong VEGFR2 inhibitory activity in silico screening combined with in vitro experimental validation, and it has shown anti-cancer effects on some human cancer cell lines, but little is known about the anti-angiogenesis effects and anti-prostate cancer effects. In this study, we analyzed the binding modes and kinetic analysis of flubendazole with VEGFR2 and first demonstrated that flubendazole suppressed VEGF-stimulated cell proliferation, wound-healing migration, cell invasion and tube formation of HUVEC cells, and decreased the phosphorylation of extracellular signal-regulated kinase and serine/threonine kinase Akt, which are the downstream proteins of VEGFR2 that are important for cell growth. What's more, our results showed that flubendazole decreased PC-3 cell viability and proliferation ability, and suppressed PC-3 cell wound healing migration and invasion across a Matrigel-coated Transwell membrane in a concentration-dependent manner. The antiproliferative effects of flubendazole were due to induction of G2-M phase cell cycle arrest in PC-3 cells with decreasing expression of the Cyclin D1 and induction of cell apoptosis with the number of apoptotic cells increased after flubendazole treatment. These results indicated that flubendazole could exert anti-angiogenic and anticancer effects by inhibiting cell cycle and inducing cell apoptosis.

Combination of RNA-seq and proteomics reveals the mechanism of DL0410 treatment in APP/PS1 transgenic mouse model of Alzheimer's disease.

There is a lack of a systematic understanding of the specific mechanism of action of DL0410 in AD treatment. In this study, the combination of RNA-seq and proteomics was firstly employed to uncover the mechanism of action of DL0410 in APP/PS1 transgenic mice. The results of behavioral tests showed that oral administration of DL0410 for 8 weeks improved memory and cognition of APP/PS1 mice. DL0410 significantly reduced ß-amyloid deposition and resulted in significant upregulation of synaptophysin, PSD95 and NMDAR/ CaMKⅡ signaling pathway in the hippocampus and cortex, indicating that DL0410 improved synaptic plasticity in APP/PS1 mice, which agrees with the results of RNA-seq and proteomics. Furthermore, the enrichment results of differentially expressed genes identified by RNA-seq and proteomics demonstrate the potential protective effects of DL0410 against oxidative stress and mitochondrial dysfunction. As expected, DL0410 dose-dependently ameliorated oxidative damage and markedly increased the expression of PGC-1α, TFAM, SOD1 and SOD2. Mitochondrial high-resolution respirometry results revealed that mitochondrial respiratory function was significantly improved in APP/PS1 mice administered with DL0410. In addition, DL0410 treatment reduced oxidative damage, strengthened antioxidant system and improved mitochondrial function in Aß-induced HT22 cells. Altogether, our findings suggest the potential of DL0410 as a novel candidate for AD treatment.

The Association of Allergy-Related and Non-Allergy-Related Olfactory Impairment with Cognitive Function in Older Adults: Two Cross-Sectional Studies.

BACKGROUND: Evidence on the association of Olfactory Impairment (OI) with age-related cognitive decline is inconclusive, and the potential influence of allergy remains unclear. OBJECTIVE: We aimed to evaluate the cross-sectional associations of allergy-related and non-allergy- related OI to cognitive function. METHODS: We included 2,499 participants from the Health and Retirement Study (HRS)-Harmonized Cognitive Assessment Protocol (HCAP) sub-study and 1,086 participants from the English Longitudinal Study of Ageing (ELSA)-HCAP. The Olfactory Function Field Exam (OFFE) using Sniffin' Stick odor pens was used to objectively assess olfactory function and an olfactory score <6/11 indicated OI. Mini-Mental Status Examination (MMSE) was used to assess global cognitive function and define cognitive impairment (<24/30). A neuropsychologic battery was used to assess five cognitive domains. RESULTS: Compared to non-OI participants, individuals with OI had lower MMSE z-score [ßHRS = -0.33, 95% Confidence Interval (CI): -0.41 to -0.24; ßELSA = -0.31, -0.43 to -0.18] and higher prevalence of cognitive impairment [Prevalence Ratio (PR)HRS = 1.46, 1.06 to 2.01; PRELSA = 1.63, 1.26 to 2.11]. The associations were stronger for non-allergy-related OI (ßHRS = -0.36; ßELSA = -0.34) than for allergy-related OI (ßHRS = -0.26; ßELSA = 0.13). Similar associations were observed with domain- specific cognitive function measures. CONCLUSION: OI, particularly non-allergy-related OI, was related to poorer cognitive function in older adults. Although the current cross-sectional study is subject to several limitations, such as reverse causality and residual confounding, the findings will provide insights into the OI-cognition association and enlighten future attention to non-allergy-related OI for the prevention of potential cognitive impairment.

Observation of the curative effect of scleral suture fixation technique with four-loop foldable intraocular lens.

The objective of the study was to evaluate the curative effect of a modified technique of scleral suture fixation with a four-loop foldable intraocular lens (IOL) for eye with inadequate capsule support. This was a retrospective study of 22 eyes with inadequate capsule support of 20 patients who underwent the scleral suture fixation technique with 9-0 polypropylene suture and foldable four-loop IOL implant. Preoperative and follow-up data were collected for all patients. The mean follow-up was 5.08 ± 0.48 months (range: 3-12 months). The mean pre- and postoperative log of minimum angle of resolution (logMAR) uncorrected distance visual acuity was 1.11 ± 0.32 versus 0.09 ± 0.09 (P < 0.001). The mean pre- and postoperative logMAR best corrected visual acuity was 0.37 ± 0.19 versus 0.08 ± 0.07 (P < 0.001). The intraocular pressure (IOP) increased briefly (range: 21-30 mmHg) in eight eyes on the first day postoperatively and returned to normal within 1 week. No IOP drops were used postoperatively. The IOP was 12-19.3 (13.72 ± 1.28) in this follow-up, which had no significant difference compared to the preoperative IOP (t = 0.34, P = 0.74). At this follow-up, there was no hyperemia, local hyperplasia, obvious scar, suture knots, or segment ends observed under the conjunctiva, as well as no pupil deformation or vitreous hemorrhage. The mean postoperative IOL decentration degree was 0.22 ± 0.08 mm. At the 7-day follow-up postoperatively, one side of the IOL was dislocated to the vitreous cavity in one case, which was resolved by reimplantation of a new IOL in time with the same technique. Scleral suture fixation technique of a four-loop foldable IOL was a feasible operation method for an eye with inadequate capsular support.

Identification of potential biomarkers and candidate therapeutic drugs for clear cell renal cell carcinoma by bioinformatic analysis and reverse network pharmacology.

This study aims to analyze the potential biomarkers using bioinformatics technology, explore the pathogenesis, and investigate potential Chinese herbal ingredients for the Clear cell renal cell carcinoma (ccRCC), which could provide theoretical basis for early diagnosis and effective treatment of ccRCC. The gene expression datasets GSE6344 and GSE53757 were obtained from the Gene Expression Omnibus database to screen differentially expressed genes (DEGs) involved in ccRCC carcinogenesis and disease progression. Enrichment analyses, protein-protein interaction networks construction, survival analysis and herbal medicines screening were performed with related software and online analysis platforms. Moreover, network pharmacology analysis has also been performed to screen potential target drugs of ccRCC and molecular docking analysis has been used to validate their effects. Total 274 common DEGs were extracted through above process, including 194 up-regulated genes and 80 down-regulated genes. The enrichment analysis revealed that DEGs were significantly focused on multiple amino acid metabolism and HIF signaling pathway. Ten hub genes, including FLT1, BDNF, LCP2, AGXT2, PLG, SLC13A3, SLC47A2, SLC22A8, SLC22A7, and SLC13A3, were screened. Survival analysis showed that FLT1, BDNF, AGXT2, PLG, SLC47A2, SLC22A8, and SLC12A3 were closely correlated with the overall survival of ccRCC, and AGXT2, SLC47A2, SLC22A8, and SLC22A7 were closely associated with DFS. The potential therapeutic herbs that have been screened were Danshen, Baiguo, Yinxing, Huangqin and Chuanshanlong. The active compounds which may be effective in ccRCC treatment were kaempferol, Scillaren A and (-)-epigallocatechin-3-gallate.