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Abstract Background Age-related eye diseases (AREDs) have become increasingly prevalent with the aging population, serving as the leading causes of visual impairment worldwide. Epigenetic clocks are generated based on DNA methylation (DNAm) levels and are considered one of the most promising predictors of biological age. This study aimed to investigate the bidirectional causal association between epigenetic clocks and common AREDs or glaucoma endophenotypes. Methods Instrumental variables for epigenetic clocks, AREDs, and glaucoma endophenotypes were obtained from corresponding genome-wide association study data of European descent. Bidirectional two-sample Mendelian randomization (MR) was employed to explore the causal relationship between epigenetic clocks and AREDs or glaucoma endophenotypes. Multivariable MR (MVMR) was used to determine whether glaucoma endophenotypes mediated the association of epigenetic clocks with glaucoma. Multiple sensitivity analyses were conducted to confirm the robustness of MR estimates. Results The results showed that an increased intrinsic epigenetic age acceleration (HorvathAge) was significantly associated with an increased risk of primary open-angle glaucoma (OR = 1.04, 95% CI 1.02 to 1.06, P = 6.1E−04). The epigenetic age acceleration (EEA) of HannumAge was related to a decreased risk of primary angle-closure glaucoma (OR = 0.92, 95% CI 0.86 to 0.99, P = 0.035). Reverse MR analysis showed that age-related cataract was linked to decreased HannumAge (β = −0.190 year, 95% CI −0.374 to −0.008, P = 0.041). The EEA of HannumAge (β = −0.85 μm, 95% CI −1.57 to −0.14, P = 0.019) and HorvathAge (β = −0.63 μm, 95% CI −1.18 to −0.08, P = 0.024) were associated with decreased central corneal thickness (CCT). PhenoAge was related to an increased retinal nerve fiber layer thickness (β = 0.06 μm, 95% CI 0.01 to 0.11, P = 0.027). MVMR analysis found no mediation effect of CCT in the association of HannumAge and HorvathAge with glaucoma. DNAm-based granulocyte proportions were significantly associated with presbyopia, rhegmatogenous retinal detachment, and intraocular pressure (P

Abstract Background As global aging intensifies, the prevalence of ocular fundus diseases continues to rise. In China, the tense doctor-patient ratio poses numerous challenges for the early diagnosis and treatment of ocular fundus diseases. To reduce the high risk of missed or misdiagnosed cases, avoid irreversible visual impairment for patients, and ensure good visual prognosis for patients with ocular fundus diseases, it is particularly important to enhance the growth and diagnostic capabilities of junior doctors. This study aims to leverage the value of electronic medical record data to developing a diagnostic intelligent decision support platform. This platform aims to assist junior doctors in diagnosing ocular fundus diseases quickly and accurately, expedite their professional growth, and prevent delays in patient treatment. An empirical evaluation will assess the platform’s effectiveness in enhancing doctors’ diagnostic efficiency and accuracy. Methods In this study, eight Chinese Named Entity Recognition (NER) models were compared, and the SoftLexicon-Glove-Word2vec model, achieving a high F1 score of 93.02%, was selected as the optimal recognition tool. This model was then used to extract key information from electronic medical records (EMRs) and generate feature variables based on diagnostic rule templates. Subsequently, an XGBoost algorithm was employed to construct an intelligent decision support platform for diagnosing ocular fundus diseases. The effectiveness of the platform in improving diagnostic efficiency and accuracy was evaluated through a controlled experiment comparing experienced and junior doctors. Results The use of the diagnostic intelligent decision support platform resulted in significant improvements in both diagnostic efficiency and accuracy for both experienced and junior doctors (P

Abstract Background Patients with primary hyperparathyroidism (PHPT) are at risk for severe hypocalcemia (SH) following parathyroidectomy (PTX), but limited data exist on the predictors of SH. We aimed to identify risk factors for early postoperative SH after PTX in patients with PHPT and to evaluate the predictive value of clinical parameters. Methods A retrospective review of patients with PHPT who underwent PTX between January 2010 and December 2022 was performed. A total of 46 patients were included in the study, with 15 (32.6%) experiencing postoperative SH, 19 (41.3%) having calculi in the ureter or kidney, and 37 (80.4%) having osteoporosis. Patients were divided into SH and non-SH groups based on postoperative serum calcium levels. Preoperative biochemical indicators, bone turnover markers, and renal function parameters were analyzed and correlated with postoperative SH. Results Statistically significant (P

As a key component of lithium-ion batteries, a separator with excellent electrolyte wettability and good thermal stability has an important impact on the overall performance of lithium-ion batteries. Herein, a PVDF/sepiolite electrospun layer was coated on one side of the PP separator via electrospinning technology to prepare the composite separator (xMS-PVDF@PP) with sepiolite nanofibers modified with vinyltriethoxysilane (VTES) to ameliorate their dispersibility and compatibility with PVDF polymer matrix. The effect of modified sepiolite addition amounts on the physical and electrochemical properties of composite separator was intensively studied. It is found that the as-prepared xMS-PVDF@PP composite separator displays enhanced porosity, electrolyte uptake, thermal stability and Li+ ion transport kinetics than pristine PP separator. Specifically, Li|LiFePO4 battery with 20MS-PVDF@PP as separator shows the best rate and cycling performance, with a specific discharge capacity of 115.3 mAh·g–1 at 10C rate and a capacity retention rate of 97.06% after 200 cycles at 1C rate. The sepiolite in the electrospun layer can immobilize PF6– anion to facilitate the uniform distribution of Li+ ions and then inhibit the lithium dendrite growth, as well as absorb HF to alleviate Fe2+ dissolution from LiFePO4 cathode, thereby further improving the electrochemical performance of LiFePO4 battery.

BackgroundThe association of cognitive function, its changes, and all-cause mortality has not reached a consensus, and the independence of the association between changes in cognitive function and mortality remains unclear. The purpose of this study was to evaluate the longitudinal association between baseline cognitive function and cognitive changes over 1 year with subsequent all-cause mortality among the older adults aged 60 and above.MethodsA prospective cohort study utilizing the Community Older Adults Health Survey data. Initiated in 2018, the study annually assessed all individuals aged 60+ in Dalang Town, Dongguan City. Cognitive function was assessed using the Chinese version of the Mini-Mental State Examination (MMSE). A total of 6,042 older adults individuals were included, and multivariate Cox proportional hazard models were used to examine cognitive function’s impact on mortality.ResultsParticipants’ median age was 70 years, with 39% men. Over a median 3.08-year follow-up, 525 died. Mortality risk increased by 6% per MMSE score decrease (adjusted HR = 1.06, 95%CI: 1.05–1.08). Compared to those with normal cognitive function at baseline, participants with mild cognitive impairment and moderate to severe cognitive impairment had significantly higher mortality risks (adjusted HR = 1.40, 95%CI: 1.07–1.82; HR = 2.49, 95%CI: 1.91–3.24, respectively). The risk of death was 5% higher for each one-point per year decrease in cognitive function change rate (HR = 1.05, 95%CI: 1.02–1.08). Compared with participants with stable cognitive function, those with rapid cognitive decline had a 79% increased risk of death (adjusted HR = 1.79, 95% CI: 1.11–2.87), with baseline cognitive function influencing this relationship significantly (P for interaction = 0.002).ConclusionBaseline cognitive impairment and rapid cognitive decline are associated with higher all-cause mortality risks in Chinese older adults. Baseline function influences the mortality impact of cognitive changes.

This paper addresses the problem of containment control for second-order multi-agent systems with position constraints, time delays, and switching graphs. The approach involves treating position constraints with a scaling factor and transforming the system into a new one through model transformations. Based on the analysis of Lyapunov function, it is demonstrated that all followers will eventually enter the convex hull formed by the leaders, as long as there exists at least a directed path to one of the leaders for all followers in the union of the communication graphs. Finally, numerical results are presented to validate the effectiveness of the algorithm.

Background: Renal fibrosis is the main cause of the development of diabetic kidney disease (DKD). ACSL1 plays an important role in colon cancer and liver fibrosis. Methods: We screened ACSL1 by proteomics analysis and then verified the expression of ACSL1 in the urine of diabetic nephropathy patients by WB and ELISA. Then, a total of 12 db/m and db/db mice were used to verify the association between renal fibrosis and ACSL1. Periodic acid-Schiff (PAS) staining, Masson staining, and immunostaining were performed for histological studies. The relationship between ACSL1 and renal fibrosis was studied by knocking down ACSL1 in cell experiments. Results: The expression of ACSL1 was significantly increased in the exfoliated urine cells and urine supernatant of diabetic nephropathy patients and was closely related to renal function. In addition, the expression of ACSL1 was significantly increased in the renal tissues of db/db mice with fibrosis. Knocking down ACSL1 in HK-2 cells was shown to reverse renal fibrosis induced by high glucose. Conclusions: We found a potential therapeutic target for preventing or ameliorating the progression of DKD fibrosis. Reducing ACSL1 expression may be a new strategy for the treatment of renal fibrosis caused by DKD, which provides an experimental theoretical basis for new drug research. Resumen: Antecedentes: La fibrosis renal es la causa principal de desarrollo de nefropatía diabética (ND). ACSL1 juega un papel importante en el cáncer de colon y la fibrosis hepática. Métodos: Cribamos ACSL1 mediante análisis proteómico, verificando seguidamente la expresión de ACSL1 en la orina de los pacientes con nefropatía diabética mediante WB y ELISA. A continuación, utilizamos un total de 12 ratones db/m y db/db para verificar la asociación entre fibrosis renal y ACSL1. Se realizaron tinciones PAS (Periodic acid-Schiff), de Masson e inmunotinción para los estudios histológicos. Estudiamos la relación entre ACSL1 y fibrosis renal aplicando la técnica de knockdown a ACSL1 en los experimentos celulares. Resultados: La expresión de ACSL1 se incrementó significativamente en las células de orina exfoliada y el sobrenadante de orina de los pacientes con nefropatía diabética y estuvo estrechamente relacionada con la función renal. Además, la expresión de ACSL1 se incrementó significativamente en los tejidos renales de los ratones db/db con fibrosis. La realización de knockdown a ACSL1 en las células HK-2 reflejó una reversión de la fibrosis renal inducida por la alta tasa de glucosa. Conclusiones: Encontramos un objetivo terapéutico potencial para prevenir o mejorar la progresión de la fibrosis en la ND. Reducir la expresión de ACSL1 puede suponer una nueva estrategia para el tratamiento de la fibrosis renal causada por la ND, lo cual aporta una base teórica experimental para la investigación de un nuevo fármaco.

BackgroundLinear associations between circulating insulin-like growth factor-1 (IGF-1) levels and Parkinson’s disease (PD) have been evidenced in observational studies. Yet, the causal relationship between IGF-1 levels and PD remains obscure. We conducted Mendelian randomization to examine the correlation between genetically predicted IGF-1 levels and PD.MethodsBy reviewing genome-wide association studies (GWAS) that are publicly accessible, we uncovered SNPs linked to both serum concentrations of IGF-1 and PD. A two-sample Mendelian randomization (MR) analysis was carried out to evaluate the individual effect of IGF-1 on PD.ResultsIn a primary causal effects model in MR analysis, employing the inverse-variance weighted (IVW) method, IGF-1 levels exhibited a notable association with the risk of PD (OR, 1.020, 95% CI, 1.003–1.038, p = 0.0215). Multiple evaluations revealed that horizontal pleiotropy was improbable to distort the main results (MR-Egger: P PD intercept =0.719), and no bias was detected by leave-one-out analysis.ConclusionThis study unearthed evidence indicating that heightened IGF-1 levels might be causally correlated with an increased risk of PD.

“The article investigates the macro-cell corrosion behavior and corrosion resistance when the alloyed steel and the carbon steel are used together because the traditional carbon steel is difficult to meet the corrosion resistance and durability of the steel structure of the transmission line in the marine environment.” In this paper, a new type of Cr-alloyed corrosion-resistant steel (00Cr10MoV) is used to partially replace carbon structural steel in order to meet the actual needs of corrosion resistance and service life improvement of steel structures for offshore transmission lines. It is important to systematically study the macro-cell corrosion behavior of combinations of the same type of steel and dissimilar steel, induced by the chloride concentration difference in simulated concrete solutions, and employ electrochemical testing methods to scientifically evaluate the corrosion resistance of steel after macro-cell corrosion. The aim is to study and evaluate the macro-cell corrosion behavior of alloyed corrosion-resistant steel and to lay a foundation for its combined use with carbon steel in a chloride corrosion environment to improve the overall corrosion resistance and service life. Under the same concentration difference, the macro-cell corrosion of the alloyed steel combination is milder compared with the carbon steel combination. The corrosion current of the alloyed steel combination at 29 times the concentration difference is only 1/10 of the carbon steel combination. Moreover, at 29 times the concentration difference, the macro-cell corrosion potential of dissimilar steel is only 1/6 of the combined potential of carbon steel combination under the same concentration difference, and the corrosion current is only 1/10 of that of the carbon steel combination.

(1) Background: A rise in intraocular pressure (IOP) and decreased retinal ganglion cells are frequent indicators of effective modeling of chronic ocular hypertension in mice. In this study, the sensitivity of the mouse model to pharmaceutical therapy to reduce intraocular tension was assessed, the model’s safety was confirmed using a cytotoxicity test, and the success rate of the mouse model of ocular hypertension was assessed by assessing alterations in IOP and neurons in the ganglion cell layer. (2) Methods: A mouse model of chronic ocular hypertension was produced in this study by employing photocrosslinkable sericin hydrogel injection and LED lamp irradiation. The eyes of 25 C57BL/6 male mice were subjected to 405 nm UV light from the front for 2 min after being injected with 5 μL of sericin hydrogel in the anterior chamber of the left eye. IOP in the mice was measured daily, and IOP rises greater than 5 mmHg were considered intraocular hypertension. When the IOP was lowered, the intervention was repeated once, but the interval between treatments was at least 2 weeks. The right eyes were not treated with anything as a normal control group. Mice eyeballs were stained with HE, Ni-type, and immunofluorescence to assess the model’s efficacy. Two common drugs (tafluprost eye drops and timolol eye drops) were provided for one week after four weeks of stable IOP, and IOP changes were assessed to determine the drug sensitivity of the mouse model of chronic ocular hypertension. Furthermore, CellTiter 96® AQueous One Solution Cell Proliferation Assay (MTS) was utilized to investigate the safety of the ocular hypertension model by evaluating the deleterious effects of photocrosslinkable sericin hydrogel on cells. (3) Results: Before injection, the basal IOP was (9.42 ± 1.28) mmHg (1 kPa = 7.5 mmHg) in the experimental group and (9.08 ± 1.21) in the control group. After injection, cataract occurred in one eye, corneal edema in one eye, endophthalmitis in one eye, iris incarceration in one eye, and eyeball atrophy in one eye. Five mice with complications were excluded from the experiment, and twenty mice were left. Four weeks after injection, the IOP of the experimental group was maintained at (19.7 ± 4.52) mmHg, and that of the control group was maintained at (9.92 ± 1.55) mmHg, and the difference between the two groups was statistically significant (p < 0.05). Before the intervention, the IOP in the experimental group was (21.7 ± 3.31) mmHg in the high IOP control group, (20.33 ± 2.00) mmHg in the tafluprost eye drops group, and (20.67 ± 3.12) mmHg in the timolol maleate eye drops group. The IOP after the intervention was (23.2 ± 1.03) mmHg, (12.7 ± 2.11) mmHg, and (10.4 ± 1.43) mmHg, respectively. Before and after the intervention, there were no significant differences in the high-IOP control group (p > 0.05), there were statistically significant differences in the timolol eye drops group (p < 0.05), and there were statistically significant differences in the tafluprost eye drops group (p < 0.05). One week after drug withdrawal, there was no significant difference in IOP among the three groups (p > 0.05). In the high-IOP group, the protein (sericin hydrogel) showed a short strips or fragmented structure in the anterior chamber, accompanied by a large number of macrophages and a small number of plasma cells. The shape of the chamber angle was normal in the blank control group. The number of retinal ganglion cells decreased significantly 8 weeks after injection of sericin hydrogel into the anterior chamber, and the difference was statistically significant compared with the blank control group (p < 0.05). After the cells were treated with photocrosslinkable sericin hydrogel, there was no significant difference in the data of the CellTiter 96® assay kit of MTS compared with the blank control group (p > 0.05). (4) Conclusions: A mouse model of chronic intraocular hypertension can be established successfully by injecting sericin in the anterior chamber and irradiating with ultraviolet light. The model can simulate the structural and functional changes of glaucoma and can effectively reduce IOP after the action of most antihypertensive drugs, and it is highly sensitive to drugs. Sericin has no obvious toxic effect on cells and has high safety.

BackgroundGlaucoma, characterized by a high incidence and significant ocular harm, has been elucidated through various mechanisms. Excessive autophagy leading to the loss of retinal ganglion cells (RGCs) is suggested as one potential cause for visual impairment in glaucoma.MethodsA glaucoma model was established through anterior chamber injection of silicone oil in mice. RTA408 and the positive control tafluprost were administered for intervention. The efficacy was preliminarily assessed by intraocular pressure measurement. HE staining and fluorescent staining were used to assess RGC loss, while fluorescent staining and western blot were employed to evaluate the expression of Nrf2. The role of autophagy in the pathogenesis of glaucoma was investigated by artificially modulating autophagy levels.ResultsIn glaucomatous mice, RTA408 significantly reduces the apoptosis levels of RGCs and decreases RGC loss. Further investigations reveal a notable upregulation of autophagy levels in glaucomatous mice, with RGC loss being associated with autophagy. RTA408 promotes the expression of Nrf2 and downstream antioxidant molecules, enhancing the antioxidant system while downregulating mitochondrial autophagy levels. This reduces RGC apoptosis and loss, demonstrating a protective effect against glaucoma.ConclusionAutophagy mediates the occurrence of glaucoma in mice, promoting RGC apoptosis. RTA408 alleviates RGCs damage by inhibiting excessive autophagy in the context of glaucoma.

Abstract Background and Aims Distinguishing pancreatic cancer from nonneoplastic masses is critical and remains a clinical challenge. The study aims to construct a deep learning‐based artificial intelligence system to facilitate pancreatic mass diagnosis, and to guide EUS‐guided fine‐needle aspiration (EUS‐FNA) in real time. Methods This is a prospective study. The CH‐EUS MASTER system is composed of Model 1 (real‐time capture and segmentation) and Model 2 (benign and malignant identification). It was developed using deep convolutional neural networks and Random Forest algorithm. Patients with pancreatic masses undergoing CH‐EUS examinations followed by EUS‐FNA were recruited. All patients underwent CH‐EUS and were diagnosed both by endoscopists and CH‐EUS MASTER. After diagnosis, they were randomly assigned to undergo EUS‐FNA with or without CH‐EUS MASTER guidance. Results Compared with manual labeling by experts, the average overlap rate of Model 1 was 0.708. In the independent CH‐EUS video testing set, Model 2 generated an accuracy of 88.9% in identifying malignant tumors. In clinical trial, the accuracy, sensitivity, and specificity for diagnosing pancreatic masses by CH‐EUS MASTER were significantly better than that of endoscopists. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were respectively 93.8%, 90.9%, 100%, 100%, and 83.3% by CH‐EUS MASTER guided EUS‐FNA, and were not significantly different compared to the control group. CH‐EUS MASTER‐guided EUS‐FNA significantly improved the first‐pass diagnostic yield. Conclusion CH‐EUS MASTER is a promising artificial intelligence system diagnosing malignant and benign pancreatic masses and may guide FNA in real time. Trial registration number: NCT04607720.

Abstract Background Cancer cachexia is prevalent in digestive tract cancer patients and has significant impacts on prognosis; it is vital to identify individuals who are at risk of cancer cachexia to allow for appropriate evaluation and treatment. This study evaluated whether digestive tract cancer patients with a risk of cancer cachexia and who had a risk of adverse survival could be identified before abdominal surgery. Methods This large‐scale cohort study involved patients who underwent abdominal surgery between January 2015 and December 2020 to treat digestive tract cancer. Participants were allocated to the development cohort, the validation cohort, or the application cohort. Univariate and multivariate analyses of the development cohort were performed to detect distinct risk variables for cancer cachexia to create a cancer cachexia risk score. The performance of the risk score across all the three cohorts was assessed through calculating the area under the receiver operating characteristic curve (AUC), as well as calibration and decision curves. We tested how well the score predicted survival outcomes in the application cohort. Results A total of 16 264 patients (median 64 years of age; 65.9% male) were included, with 8743 in the development cohort, 5828 in the validation cohort, and 1693 in the application cohort. Seven variables were identified as independent predictive factors and were included in the cancer cachexia risk score: cancer site, cancer stage, time from symptom onset to hospitalization, appetite loss, body mass index, skeletal muscle index, and neutrophil‐lymphocyte ratio. The risk score predicting cancer cachexia owns a good discrimination, with the mean AUC of 0.760 (P 0.05). The decision curve analysis revealed net benefits of the risk score across a range of risk thresholds in the three cohorts. In the application cohort, compared with the high‐risk group, the low‐risk group experienced significantly longer overall survival [hazard ratio (HR) 2.887, P

BackgroundPatients with inflammatory bowel disease (IBD) have a higher prevalence of depression. Gut microbiota dysbiosis plays an important role in IBD and depression. However, few studies have explored the characteristic microbiota of patients with IBD and depression (IBDD), or their role in IBDD.MethodsWe performed deep metagenomic sequencing and 16S rDNA quantitative PCR to characterise the gut microbial communities of patients with IBDD and patients with IBD without depression (IBDND). We then assessed the effect of the microbiota on colitis and depression in mouse models of dextran sulfate sodium salt (DSS)-induced colitis and lipopolysaccharide (LPS)-induced depression. Furthermore, liquid chromatography–tandem mass spectrometry was used to analyse the microbiota-derived metabolites involved in gut–brain communication. Evans Blue tracer dye was used to assess blood–brain barrier (BBB) permeability.ResultsOur results showed that the faecal abundance of Bacteroides vulgatus (B. vulgatus) was lower in patients with IBDD than in those with IBDND. In the DSS-induced colitis mouse model, the B. vulgatus group showed a significantly lower disease activity index score, lesser weight loss, and longer colon length than the DSS group. Moreover, B. vulgatus relieved depression-like behaviour in the DSS-induced colitis mouse model and in the LPS-induced depression mouse model. Furthermore, the key metabolite of B. vulgatus was p-hydroxyphenylacetic acid (4-HPAA), which was found to relieve intestinal inflammation and alleviate depression-like behaviours in mouse models. By increasing the expression of the tight junction protein claudin-5 in the vascular endothelium of the BBB, B. vulgatus and 4-HPAA play critical roles in gut–brain communication.ConclusionB. vulgatus and B. vulgatus-derived 4-HPAA ameliorated intestinal inflammation and relieved depressive symptoms through the gut–brain axis. Thus, administration of B. vulgatus or 4-HPAA supplementation is a promising therapeutic strategy for treating IBD, particularly IBDD.

Abstract Background Exercise is an affordable and practical strategy to alleviate several detrimental outcomes from the aging process, including sarcopenia. The elucidation of molecular mechanisms to alleviate sarcopenia is one of the most important steps towards understanding human aging. Although microRNAs (miRNAs) regulate muscle growth, regeneration and aging, the potential role of exercise‐mediated miRNAs during the prevention and rehabilitation of skeletal muscle atrophy upon exercise interventions remains unclear. Methods A miRNA profile by miRNA sequencing for gastrocnemius muscle of a 24‐month‐old aged male rat model mimicking the naturally aging process was established through screening the differentially expressed miRNAs (DEMs) for alleviating aging‐induced skeletal muscle atrophy upon optimal exercise intervention. The screened miRNAs and hub genes, as well as biomarkers with the most significantly enriched pathways, were validated by quantitative real‐time polymerase chain reaction and western blotting. Results The sarcopenia index (SI) value and cross‐sectional area (CSA) of rats from the old control (OC) group significantly decreased when compared with the youth control (YC) group (P 1) between the YC group and the OC group. Compared with the OC group, 7, 2 and 11 miRNAs were differentially expressed in the OE, OR and OM groups after exercise interventions, respectively. Meanwhile, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the identified DEMs were primarily related to apoptosis, autophagy and the NF‐κB/MuRF1 signalling pathways (P

Background: Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignant tumor with an unfavorable prognosis. Increasing evidence indicated circRNAs were associated with the pathogenesis and progression of tumors, but data on the expression of serum exosomal circRNAs in PDAC are scarce. This study attempted to explore the prognostic value and function of serum exosomes in PDAC patients. Methods: Microarray-based circRNA expression was determined in PDAC and paired with normal serum samples, and the intersection of differentially expressed circRNAs (DECs) in serum exosomal samples and GSE79634 tissue samples was conducted. A specific CircRNA database was applied to investigate DECs binding miRNAs. Target genes were predicted using the R package multiMiR. Cox regression analyses were applied for constructing a prognostic model. The immunological characteristics analysis was carried out through the TIMER, QUANTISEQ, XCELL, EPIC, and ssGSEA algorithms. Results: 15 DECs were finally identified, and a circRNA-miRNA-mRNA network was established. A prognostic risk model was developed to categorize patients according to the risk scores. Furthermore, the association between risk score and immune checkpoint genes including CD80, TNFSF9, CD276, CD274, LGALS9, and CD44 were significantly elevated in the high-risk group, while ICOSLG and ADORA2A were upregulated in the low-risk group. Conclusions: Our results may provide new clues for the prognosis and treatment of PDAC.

To discover novel antioxidants and anticoagulants for the prevention and treatment of cardiovascular diseases remains ongoing concern. Sagittaria trifolia is a commonly consumed aquatic vegetable with highly nutritious value and wide planting area in China. Polysaccharides are the major bioactive constituents, but little information is available on anticoagulant potential. In this work, a polysaccharide from S. trifolia (PST) was modified by sulfation to produce four sulfated derivatives (SPST-1 ∼ 4), and their antioxidant and anticoagulant potentials were evaluated. Various means of analysis confirmed the success of sulfation on PST. The unmodified PST possessed notable antioxidant and pro-coagulant activities. To some extent, sulfated modification reduced the antioxidant capacity of PST with the increase of degree of substitution (DS), but for the derivative SPST-4 with moderate DS and smallest molecular weight (MW) exerted better antioxidant activity, in particular of scavenging nitrogen-containing radicals. Interestingly, sulfation reversed the innate activity of PST from pro-coagulation to anticoagulation, which highly depended on DS. The derivative SPST-3 with highest DS and moderate MW elicited promising anticoagulant potential, particularly at concentration of 5.00 mg/mL, which was superior to that of heparin (positive control) in the aspect of prolonging thrombin time and prothrombin time. Herein, the present contribution would give evidence that PST and sulfated derivatives SPST-3 and SPST-4 own potentials to be developed as hemostatic, anticoagulant, and antioxidant candidates, respectively.

COVID-19 is caused by severe acute respiratory SARS-CoV-2. Regardless of the availability of treatment strategies for COVID-19, effective therapy will remain essential. A promising approach to tackle the SARS-CoV-2 could be small interfering (si) RNAs. Here we designed the small hairpin RNA (named as shRNA688) for targeting the prepared 813 bp Est of the S protein genes (Delta). The conserved and mutated regions of the S protein genes from the genomes of the SARS-CoV-2 variants in the public database were analyzed. A 813 bp fragment encoding the most part of the RBD and partial downstream RBD of the S protein was cloned into the upstream red florescent protein gene (RFP) as a fusing gene in the pCMV-S-Protein RBD-Est-RFP plasmid for expressing a potential target for RNAi. The double stranded of the DNA encoding for shRNA688 was constructed in the downstream human H1 promoter of the plasmid in which CMV promoter drives enhanced green fluorescent protein (EGFP) marker gene expression. These two kinds of the constructed plasmids were co-transfected into HEK293T via Lipofectamine 2000. The degradation of the transcripts of the SARS-CoV-2 S protein fusing gene expressed in the transfected HEK293T treated by RNAi was analyzed by RT-qPCR with a specific probe of the targeted SARS-CoV-2 S protein gene transcripts. Our results showed that shRNA688 targeting the conserved region of the S protein genes could effectively reduce the transcripts of the S protein genes. This study provides a cell model and technical support for the research and development of the broad-spectrum small nucleic acid RNAi drugs against SARS-CoV-2 or the RNAi drugs for the other hazard viruses which cause human diseases.

Selenium (Se)-based cathode materials have garnered considerable interest for lithium-ion batteries due to their numerous advantages, including low cost, high volumetric capacity (3268 mAh cm−3), high density (4.82 g cm−3), ability to be cycled to high voltage (4.2 V) without failure, and environmental friendliness. However, they have low electrical conductivity, low coulombic efficiency, and polyselenide solubility in electrolytes (shuttle effect). These factors have an adverse effect on the electrochemical performance of Li-Se batteries, rendering them unsuitable for real-world use. In this study, we briefly examined numerous approaches to overcoming these obstacles, including selecting an adequate electrolyte, the composition of Se with carbonaceous materials, and the usage of metal selenide base electrodes. Furthermore, we examined the effect of introducing interlayers between the cathode and the separator. Finally, the remaining hurdles and potential study prospects in this expanding field are proposed to inspire further insightful work.

Abstract Background Tamoxifen treatment may induce dysregulation of estrogen homeostasis, leading to the occurrence of related adverse reactions. However, the potential mechanisms are still unclear. The purpose of the present study was to uncover whether tamoxifen treatment would act on estrogen metabolism-related biological enzymes and the regulatory effect on estrogen homeostasis to clarify the key factors and potential mechanisms of adverse reactions caused by long-term use of tamoxifen. Method Female SD rats were administrated with tamoxifen CMC-Na solution (p.o.) once daily for four weeks and then housed at room temperature. Serum, breast, liver, uterus, and ovarian tissues were obtained, and the effects of tamoxifen administration on estrogen homeostasis, the expression, and activity of estrogen metabolic enzyme were evaluated. Results Compared with the control group, the estrogen homeostasis was disturbed and the expression and activity of UGT2B1 (homology with human UGT2B7) were significantly reduced in the rats administrated with tamoxifen. The inhibitory effect of tamoxifen on UGT2B7 was dominated by hydrophobic and π-π stacking interactions, resulting in a concentration-dependent inhibition of UGT2B7 activity by tamoxifen and the imbalance of ligand-activated transcription factors, leading to abnormal regulation of UGT2B and disturbance of estrogen homeostasis, which in turn led to adverse reactions of tamoxifen. Conclusion We established links between estrogen metabolism and tamoxifen administration and we proposed that the UGT2B inhibition was involved in the disturbance of estrogen homeostasis and the occurrence of tamoxifen-related adverse reactions.

BackgroundThe mechanism of copper-induced cellular death was newly discovered and termed cuproptosis. Inducing cuproptosis in cancer cells is well anticipated for its curative potential in treating tumor diseases. However, ferredoxin 1 (FDX1), the core regulatory gene in cuproptosis, is rarely studied, and the regulation of FDX1 in tumor biology remains obscure. A comprehensive pan-cancer analysis of FDX1 is needed.MethodsThirty-three types of tumors were included with paired normal tissues in The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) datasets. The interaction between transcription, protein, phosphorylation, and promoter methylation levels was analyzed. Survival, immune infiltration, single-cell FDX1 expression, FDX1-related tumor mutational burden (TMB), microsatellite instability (MSI), stemness, tumor immune dysfunction and exclusion (TIDE), and immunotherapy-related analyses were performed. FDX1 protein expression was assessed by kidney renal clear cell carcinoma (KIRC) tissue microarray immunohistochemistry. The function of FDX1 in KIRC was further explored by experiments in 786-O cell lines in vitro.ResultsFDX1 is highly expressed in 15 tumor types and lowly expressed in 11 tumor types. The corresponding changes in protein expression, phosphorylation, and promoter methylation level of FDX1 have been described in several tumors. Survival analysis showed that FDX1 was related to favorable or poor overall survival in eight tumors and progression-free survival in nine tumors. Immune infiltration and single-cell analysis indicated the indispensable role of FDX1 expression in macrophages and monocytes. Multiple established immunotherapy cohorts suggested that FDX1 may be a potential predictor of treatment effects for tumor patients. Tissue microarray analysis showed decreased FDX1 expression in KIRC patients’ tumor tissues. Knockdown of FDX1 resulted in the downregulation of cuproptosis in kidney renal clear tumor cells. Mechanistically, the FDX1-associated gene expression signature in KIRC is related to the enrichment of genes involved in the tricarboxylic acid (TCA) cycle, NOTCH pathway, etc. Several NOTCH pathway genes were differentially expressed in the high- and low-FDX1 groups in KIRC.ConclusionOur analysis showed that the central regulatory gene of cuproptosis, FDX1, has differential expression and modification levels in various tumors, which is associated with cellular function, immune modulation, and disease prognosis. Thus, FDX1-dependent cuproptosis may serve as a brand-new target in future therapeutic approaches against tumors.

Study region: The North and South Sources in the upper stream of Qiantang River Basin, China. Study focus: Identifying the relative contribution of climate change and human activities to runoff variation is essential for an enhanced understanding on efficient management of regional water resources. We used multiplied abrupt change testing methods to determine the baseline period (BP) and two variation periods (VP1 and VP2) and used six Budyko-based methods to detect the quantitative hydrological response to climate change and human activities. New hydrological insights for the region: The annual mean runoff of North Source witnessed a decrease in VP1 before it increased during VP2, while it continued to increase in South Source. The climate change dominated the runoff variation in the North Source, while it was human activities that was the main driver for South Source.The human-induced effect contributed to runoff decline in North Source, while it led to the continuous runoff increasing in South Source. It shows that the runoff change due to climate was more sensitive to precipitation than potential evapotranspiration. The land use analysis illustrates that human-induced runoff changes were composed of two aspects: 1) the increased proportion of woodland and decreased ratio of farmland reduced runoff; 2) the increased percentage of town-and-country-land increased runoff. The former influence was relatively limited compared to the latter, as well as the climate change.

Abstract Background The pathogenesis of myopia has been found to be associated with the blood supply of the choroid. This study aimed to determine the relationship between the distribution pattern of choroidal remodeling and the degree of myopia in young patients. Methods Young patients (age -0.5D, − 0.5 ~ − 3.0D, − 3.01 ~ − 6.0D, and

Summary: Background: Crohn's disease (CD) is a chronic inflammatory disorder characterized by intestinal immune dysfunction. Multiple factors, including gut dysbiosis, are involved in the pathogenesis of CD. However, the effect of commensal bacteria on controlling the inflammatory response in individuals with CD remains unclear. Methods: We detected Toll-like receptor 2 (TLR2), TLR4, and TLR5 expression in Roseburia intestinalis (R. intestinalis)-treated mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. Then, we quantified the signs of colonic inflammation, the proportion of regulatory T cells (Tregs) and the expression of thymic stromal lymphopoietin (TSLP) and transforming growth factor (TGF)-β in TLR-5-deficient (Tlr5−/−) mice, bone marrow chimera mice (generated using wild-type (WT) and Tlr5−/− mice), and anti-TSLP/anti-TGFβ-treated C57BL/6 mice with colitis induced by TNBS. In vitro, we used the lipopolysaccharide (LPS)-stimulated human intestinal epithelial cell line Caco-2 as an inflammatory colon cell model treated with or without the TLR5-siRNA intervention in the presence of R. intestinalis and incubated human monocyte-derived dendritic cells (DCs) with the supernatant of Caco-2 cells. Then, we cocultured human CD4+ T cells with the aforementioned DCs to determine the differentiation of Tregs. Additionally, samples from patients with CD were collected to analyse the correlation between TLR5/TSLP/TGFβ expression and the percentage of R. intestinalis. Findings: Here, we show that R. intestinalis inhibits the development of CD by increasing the differentiation of anti-inflammatory Tregs. Mechanistically, R. intestinalis stimulates TSLP production in intestinal epithelial cells (IECs) through TLR5 but not TLR2 or TLR4. TSLP produced by IECs specifically induces the secretion of interleukin-10 (IL-10) and TGFβ from DCs, which is necessary for subsequent Treg differentiation. Consequently, the depletion of TLR5 (using Tlr5−/− mice) or inhibition of TSLP (using anti-TSLP neutralizing antibodies) attenuates the protective effect of R. intestinalis on experimental colitis in mice. Importantly, the expression of TSLP in patients with CD is positively correlated with the level of R. intestinalis. Interpretation: These findings reveal the previously unknown mechanism of R. intestinalis-mediated intestinal immune regulation, which may provide the basis for new therapeutic strategies for CD. Funding: This work was funded by the National Natural Science Foundation of China (81670504 and 81970494), the Key Project of Research and Development Plan of Hunan Province (2019SK2041) and the Changsha Municipal Natural Science Foundation (kq2014258).

ObjectiveThis meta-analysis comprehensively evaluated the association between hypertensive disorders in pregnancy (HDP) and the risk of developing chronic hypertension and the associations between specific types of HDP, including preeclampsia (PE) and gestational hypertension (GH), and the risk of developing chronic hypertension.DesignSystematic review and meta-analysis.Data SourcesThe PubMed, Embase and Cochrane Library databases were searched from inception to August 20, 2021.MethodsDepending on heterogeneity, the combined odds ratio (OR) of the 95% confidence interval (CI) was obtained with a random-effects or fixed-effects model. We used meta-regression analysis to explore the sources of heterogeneity. We analyzed the OR value after adjusting for age and BMI at recruitment, prepregnancy BMI, age at first delivery, and other factors. Additionally, we evaluated the results of the subgroup analysis by the year of publication (< 2016, ≥ 2016), study design, sample size (< 500, ≥ 500), region (North and South America, Europe, and other regions) and NOS score (< 7, ≥ 7).ResultsOur systematic review and meta-analysis comprehensively explored the relationships between HDP, GH, and PE and chronic hypertension. Twenty-one articles that included 634,293 patients were included. The results of this systematic review and meta-analysis suggested that women with a history of HDP are almost 3.6 times more likely to develop chronic hypertension than those without a history of HDP, women with a history of GH are almost 6.2 times more likely to develop chronic hypertension than those without a history of GH, and women with a history of PE are almost 3.2 times more likely to develop chronic hypertension than those without a history of PE. In addition, we further calculated the probability of developing chronic hypertension among patients with HDP or PE after adjusting for age and BMI at recruitment, prepregnancy BMI, age at first delivery, and other factors. The results suggested that women with a history of HDP are almost 2.47 times more likely to develop chronic hypertension than those without a history of HDP and that women with a history of PE are almost 3.78 times more likely to develop chronic hypertension than those without a history of PE. People in Asian countries are more likely to develop chronic hypertension after HDP or PE, while American people are not at high relative risk.ConclusionThese findings suggest that HDP, GH, and PE increase the likelihood of developing chronic hypertension. After adjustment for age and BMI at recruitment, prepregnancy BMI, age at first delivery, and other factors, patients with HDP or PE were still more likely to develop chronic hypertension. HDP may be a risk factor for chronic hypertension, independent of other risk factors. GH and PE, as types of HDP, may also be risk factors for chronic hypertension.Systematic Review Registration[www.ClinicalTrials.gov], identifier [CRD42021238599].

Abstract To dispose the fragility and poor conductivity problems of SiO‐based anode materials, a “phase change mediation combined with cord reinforcing” concept is proposed, in which graphene cord is in situ fabricated combined with Si and SiO2 nanodomains generated in the SiO matrix via chemical vapor deposition. Being the fabricated composite, graphene cord not only bridges but also wraps the SiO particles, improving the electrical conductivity and flexibility of the fabricated SiO@Gra anode. Moreover, the increased SiO2 regions in the Si/SiO matrix alleviate volume change and release the strain for Li+ insertion, enhancing the tenacity of the SiO electrode according to the phase transformation flexibility mechanism. Besides, the grain boundaries and interfaces among the Si/SiO2/SiO regions contribute to additional Li+ storage and pledge more channels for Li+ transfer and electrolyte wetting. The merit of Si/SiO2/SiO synergistically contributes to the ascendant electrochemical performance of the SiO anodes. The as‐fabricated SiO@Gra anodes deliver a high reversible capacity of 1127 mAh g−1 at 0.2 A g−1 with 87% capacity retention after 200 cycles. The proposed phase change and cord reinforcing not only deepen the understanding of the electrochemical reaction mechanism of Li+ in SiO, but also inspire a rational design tactic for advanced lithium‐ions batteries.

Background: Patients with Crohn’s disease (CD) experience severely reduced quality of life, particularly those who do not respond to conventional therapies. Antitumor necrosis factor (TNF)α is commonly used as first-line therapy; however, many patients remain unresponsive to this treatment, and the identification of response predictors could facilitate the improvement of therapeutic strategies.Methods: We screened Gene Expression Omnibus (GEO) microarray cohorts with different anti-TNFα responses in patients with CD (discovery cohort) and explored the hub genes. The finding was confirmed in independent validation cohorts, and multiple algorithms and in vitro cellular models were performed to further validate the core predictor.Results: We screened four discovery datasets. Differentially expressed genes between anti-TNFα responders and nonresponders were confirmed in each cohort. Gene ontology enrichment revealed that innate immunity was involved in the anti-TNFα response in patients with CD. Prediction analysis of microarrays provided the minimum misclassification of genes, and the constructed network containing the hub genes supported the core status of TLR2. Furthermore, GSEA also supports TLR2 as the core predictor. The top hub genes were then validated in the validation cohort (GSE159034; p < 0.05). Furthermore, ROC analyses demonstrated the significant predictive value of TLR2 (AUC: 0.829), TREM1 (AUC: 0.844), and CXCR1 (AUC: 0.841). Moreover, TLR2 expression in monocytes affected the immune–epithelial inflammatory response and epithelial barrier during lipopolysaccharide-induced inflammation (p < 0.05).Conclusion: Bioinformatics and experimental research identified TLR2, TREM1, CXCR1, FPR1, and FPR2 as promising candidates for predicting the anti-TNFα response in patients with Crohn’s disease and especially TLR2 as a core predictor.

BackgroundSkeletal muscle mass deterioration is common in gastric cancer (GC) patients and is linked to poor prognosis. However, information regarding the effect of skeletal muscle mass changes in the postoperative period is scarce. This study was to investigate the link between postoperative loss of skeletal muscle mass and survival following GC surgery.MethodsPatients who underwent GC surgery between January 2015 and December 2016 were recruited into the study. Computed tomography at L3 vertebral level was used to examine skeletal muscle index prior to surgery and about 6 months after surgery. Skeletal muscle index changes were categorized as presence or absence of ≥5% loss. Overall survival (OS) and disease-free survival (DFS) were analyzed, and Cox proportional hazard models used to identify their predictors.ResultsThe study comprised of 318 gastric cancer patients of which 63.5% were male. The group's mean age was 58.14 ± 10.77 years. Sixty-five patients experienced postoperative skeletal muscle index loss ≥5% and had poorer OS (P = 0.004) and DFS (P = 0.020). We find that postoperative skeletal muscle index loss ≥ 5% predicts OS [hazard ratio (HR): 2.769, 95% confidence interval (CI): 1.865–4.111; P < 0.001] and DFS (HR: 2.533, 95% CI: 1.753–3.659; P < 0.001).ConclusionsLoss of skeletal muscle mass postoperatively is linked to poor survival following GC surgery. Further studies are needed to determine whether stabilizing or enhancing skeletal muscle mass after surgery improves survival.

To research the deterioration of the mechanical properties of stirrup-corroded concrete columns under the effect of load and chloride, accelerated corrosion and load carrying capacity tests were carried out on concrete columns subjected to long-term axial loading by means of dry and wet cycles with extra electric currents. The test results showed that under the effect of axial load and chloride, the corrosion-induced cracks of stirrup-corroded concrete columns mainly developed along the direction of the longitudinal reinforcing steel bars (cracks along longitudinal reinforcing steel bars caused by corrosion) and there were almost no corrosion-induced cracks along the direction of the corroded stirrups. The length and maximum width of the corrosion-induced cracks increased with the stirrup corrosion rate, but the average width of the corrosion-induced cracks did not change significantly. After the stirrup-corroded column reached the ultimate load, the concrete cover spalled off in pieces along the corrosion-induced cracks and loading cracks, the core concrete was crushed, and the test column produced obvious brittle failure. With the increase in the corrosion rate of stirrups, the stiffness and ultimate bearing capacity of the column decreased. Considering factors such as damage to the column section caused by stirrup corrosion, the decrease in the lateral restraint effect of the corroded stirrup on the longitudinal reinforcing steel bars, and buckling of the longitudinal reinforcing steel bars, the ultimate bearing capacity prediction model of the short column subjected to axial compression due to stirrup corrosion was established. The calculated values of the model were in good agreement with the measured values, indicating the model has good applicability.

According to previous studies, the Lixiahe area in the east of the Jianghuai River was an alternate environment of land and sea in the middle Holocene, and it was not until the late Holocene that the eastern Jianghuai completely became a terrestrial environment. However, recent archaeological studies have found that the extensive Neolithic sites in the Lixiahe area have recorded the rich human activities and cultural connotations of the prehistoric civilization in the Middle Holocene. In this paper, the Gangxi section of Jianhu Lake, Jiangsu Province (GX2) was selected and pollen analysis was fulfilled, then the geomorphic evolution process of the study area from sea to land was investigated according to the palynological assemblages and algae fossils of brackish water, semi-saline water, fresh water and terrestrial in the section strata. During the period of 8500–3800 cal. BP, GX2 was affected by multiple factors such as sea surface fluctuation, ocean flow and sediment deposition carried by seagoing rivers. Since 5800 cal. BP, the area east of the Grand Canal between the Yangtze River and the Huaihe River, and the west of the Yangzhai town, Funing–Longgang town, Yancheng–Dagang town and Yancheng–west of the Dongtai–Hai’an line, have become a terrestrial environment. After the eastern Jianghuai became a land, the Liangzhu culture (5300–4300 cal. BP) in the Taihu Lake basin in the south wing of the Yangtze River delta expanded to the eastern Jianghuai area, and the Longshan culture and Yueshi culture in the Haidai area in the north also migrated south to the eastern Jianghuai area. Admittedly, the main reason in the process of Neolithic cultural development is the internal motivation that the ancient ancestors struggled with nature and pushed forward the continuous development of civilizations. However, our study explains the palaeogeographical origin of Neolithic culture in the eastern and coastal areas of Jianghuai in the middle Holocene, and meanwhile, provides an example for the man–land relationship research on Neolithic culture.

DNA methylation patterns are essential in understanding carcinogenesis. However, the relationship between DNA methylation and the immune process has not been clearly established—this study aimed at elucidating the interaction between glioma and DNA methylation, consolidating glioma classification and prognosis. A total of 2,483 immune-related genes and 24,556 corresponding immune-related methylation probes were identified. From the Cancer Genome Atlas (TCGA) glioma cohort, a total of 683 methylation samples were stratified into two different clusters using unsupervised clustering, and eight types of other cancer samples from the TCGA database were shown to exhibit excellent distributions. A total of 3,562 differentially methylated probes (DMPs) were selected and used for machine learning. A five-probe signature was established to evaluate the prognosis of glioma as well as the potential benefits of radiotherapy and Procarbazine, CCNU, Vincristine (PCV) treatment. Other prognostic clinical models, such as nomogram and decision tree, were also evaluated. Our findings confirmed the interactions between immune-related methylation patterns and glioma. This novel approach for cancer molecular characterization and prognosis should be validated in further studies.

Hantaan virus (HTNV), the causative pathogen of hemorrhagic fever with renal syndrome (HFRS), is a negative RNA virus belonging to the Orthohantaviridae family. HTNV envelope glycoprotein (GP), encoded by the genomic medium segment, is immunogenic and is therefore a promising vaccine candidate. Major histocompatibility complex class I (MHC-I) epitopes derived from HTNV has been extensively studied, but little is known of MHC-II epitopes. In silico predictions based on four databases indicated that the full-length HTNV GP has 1121 15-mer epitopes, of which 289 had a high score for binding to the human and murine MHC-II superfamily. It found that epitope ILTVLKFIANIFHTS could potentially bind most MHC-II molecules covering human and murine haplotypes. Dominant epitopes were validated by enzyme-linked immunospot assay of splenocytes from immunized mice; 6 of 10 epitopes supported the predictions including TATYSIVGPANAKVP, TKTLVIGQCIYTITS, FSLLPGVAHSIAVEL, CETYKELKAHGVSCP, CGLYLDRLKPVGSAY, and NLGENPCKIGLQTSS. Conservation analysis of dominant epitopes revealed host–virus interactions without geographic stratification, thus meeting the requirements of candidate vaccines for large-population prophylaxis. These findings provide insight into hantavirus antigenicity and suggest that vaccines targeting MHC-II could provide immune protection in large population to complement symptomatic therapies for the treatment of HFRS.

In this paper, a containment problem is investigated for sampled-data agent networks subject to switching topologies and information delays. A nonlinear algorithm is introduced to ensure that the agents move into a convex area formed by some static leaders. The analytical approaches include the model transformation, the convexity analysis, and the Lyapunov approach. It proves that the containment problem can be achieved for sampled-data agent networks with bounded information delays and switching topologies if the union of the communication graphs has spanning trees. A numerical example is employed to demonstrate the validity of the theoretical results.

The intestinal microbiota is thought to be an important biological barrier against enteric pathogens. Its depletion, however, also has curative effects against some viral infections, suggesting that different components of the intestinal microbiota can play both promoting and inhibitory roles depending on the type of viral infection. The two primary mechanisms by which the microbiota facilitates or inhibits viral invasion involve participation in the innate and adaptive immune responses and direct or indirect interaction with the virus, during which the abundance and composition of the intestinal microbiota might be changed by the virus. Oral administration of probiotics, faecal microbiota transplantation (FMT), and antibiotics are major therapeutic strategies for regulating intestinal microbiota balance. However, these three methods have shown limited curative effects in clinical trials. Therefore, the intestinal microbiota might represent a new and promising supplementary antiviral therapeutic target, and more efficient and safer methods for regulating the microbiota require deeper investigation. This review summarizes the latest research on the relationship among the intestinal microbiota, anti-viral immunity and viruses and the most commonly used methods for regulating the intestinal microbiota with the goal of providing new insight into the antiviral effects of the gut microbiota.

Polyurethane-acrylate/SiO2 composite (SPUA) emulsions were synthesized by in situ polymerization accompanying the sol-gel process, in which the hydrolysis reaction and polymerization of monomers could be accomplished at the same time. The particle morphology of the SPUA emulsions was observed by scanning electron microscopy and transmission electron microscopy. The particle diameter was measured on a laser particle size analyzer. The molecular structure of the copolymers was characterized by Fourier transform infrared spectrometer (FTIR). Furthermore, tensile testing machine, Shore durometer, and thermogravimetric analyzer were used to investigate the mechanical properties, hardness, and thermal properties. The results indicated that, by increasing the mass fraction of tetraethyl orthosilicate (TEOS), the mechanical properties of the films were improved remarkably. When the weight % of TEOS was 8% in the SPUA emulsion, the water absorption of obtained film was 2.1%, the tensile strength was 16.8 MPa, the shore hardness was 94, and the temperature for the maximal thermal mass-loss rate was 416°C.

A microwave photonic mixer based on a frequency-doubled local oscillator (LO) is proposed. The carrier-suppressed single-sideband (CS-SSB) modulation of the -first-order radio frequency (RF) and ±second-order LO sidebands can be generated by using a dual-polarization dual-parallel Mach-Zehnder modulator (DP-DPMZM), an electrical 90° hybrid coupler, and an optical bandpass filter. The upconverted intermediate frequency (IF) signal with the frequency of ωRF + 2ωLO is output by frequency beat at a photodetector. Meanwhile, the -first-order RF sideband can be easily changed to +first-order RF sideband by adjusting one dc bias voltage of the DP-DPMZM. The downconverted IF signal with the frequency of ωRF 2ωLO is obtained correspondingly. The experimental results show that the spur suppression ratios of upconverted and downconverted IF signal are 19.0 dB and 25.5 dB, respectively. The spurious-free dynamic range of the proposed mixer is 96.5 dB·Hz2/3. The output electrical spectrums are pure owing to the optimal design of the CS-SSB modulation. The proposed mixer reduces the frequency requirement of LO signal since the second-order LO single sideband is used, and the upconversion and downconversion can be switched to each other by a simple electrical operation.

An all-optical microwave photonic frequency downconverter with tunable full range continuous phase shift is presented. In the proposed system, the radio frequency (RF) and local oscillator (LO) signals modulate two sub Mach-Zehnder modulators (MZMs) in an integrated dual-parallel MZM (DPMZM), respectively. The two sub-MZMs are both biased at the minimum transmission point to implement the carrier-suppressed double-sideband modulation. An optical bandpass filter is then used to retain the +1st order RF and LO sidebands. When the two sidebands are send to a photodetector, an intermediate frequency (IF) signal is produced, and the phase of the converted IF signal is linearly changed by adjusting the bias voltage of the parent MZM in the DPMZM. An experiment is carried out. An RF signal can be downconverted to a phase-tunable IF signal, and the measured spurious-free dynamic range reaches 100.2 dB·Hz2/3. The phase deviation and power ripple of the IF signal are less than 2° and 0.26 dB, respectively. The all-optical design makes the system bandwidth unlimited by electrical components. Meanwhile, since the proposed microwave photonic link can simultaneously implement frequency downconversion and full range phase shift of the converted IF signal, it provides a compact alternative for the applications including radio-over-fiber system and phased-array beamforming.

A high speed vehicle passing through the atmosphere may encounter radio communication blackout, a phenomenon which is caused by the high plasma density in the plasma layer surrounding the vehicle. To alleviate blackout, a method known as time-varying electromagnetic mitigation of the plasma (TEMP) is proposed. The principle of TEMP is based on a one-dimensional axisymmetric model consisting mainly of the ion mass conservation equation, the ion momentum conservation equation, the generalized Ohm's law and the electromagnetic induction law. Numerical simulations were performed to examine the plasma mitigation effects under various conditions by assuming a linearly decreasing magnetic field. Simulation results suggested that the plasma density at the center was reduced to less than 0.2 times the original plasma density but was of sufficient size (about 3 cm) and time duration (about 50 μs) to permit data transmission at pressures as high as 50 Pa. Furthermore, it is suggested that a lower pressure, stronger magnetic field and shorter duration are helpful for plasma mitigation, achieving nearly the same effect as that obtained at different plasma densities. Given that a dc magnet or a dc electric field is not required, and the power requirement and weight are modest, the TEMP approach based on applying a periodic magnetic pulse may be a promising way to alleviate radio communication blackout.