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Background: The burden of nonalcoholic fatty liver disease (NAFLD) is growing in patients with chronic hepatitis B (CHB). NAFLD is typically associated with obesity, however, it is increasingly being identified in non-obese patients. This study aimed to investigate disease severity and antiviral response in non-obese patients with CHB with NAFLD (CHB + NAFLD). Methods: A total of 809 patients with CHB + NAFLD were prospectively recruited and followed up for 3 years. NAFLD was diagnosed by transient elastography and defined as controlled attenuation parameter ≥248 dB/m, in the absence of excessive alcohol intake. Obesity status was defined by the Asian body mass index (BMI) cutoff of 25 kg/m2. Metabolic abnormality was defined by the presence of dyslipidemia, hypertension or diabetes. Fibrosis staging was defined according to the EASL-ALEH guidelines, with fibrosis progression defined as ≥1-stage increment. Results: In the total cohort (median age 40 years, 59.0% antiviral-treated), 33.3% were non-obese. Non-obese patients were less metabolically abnormal than obese patients (60.2% vs 72.0%, P = 0.003). After 3-year follow up, the rate of fibrosis progression was comparable between non-obese and obese patients (17.5% vs 21.9% in the total cohort, P = 0.145; 15.7% vs 14.6% in antiviral-treated cohort with persistent viral suppression, P = 0.795). No significant differences in virological and biochemical responses were observed between non-obese and obese patients (P >0.05 for all). Conclusion: Approximately one third of CHB + NAFLD patients were non-obese. Non-obese patients, while less metabolically abnormal, had a similar risk for fibrosis progression as obese patients. Obesity status did not impact the efficiency of antiviral therapy.

Abstract Background Diabetic retinopathy (DR) is the foremost cause of vision loss among the global working-age population, and statins are among the most frequently prescribed drugs for lipid management in patients with DR. The exact relationship between statins and DR has not been determined. This study sought to validate the causal association between statins usage and diabetic retinopathy. Methods The summary-data-based Mendelian randomization (SMR) method and inverse-variance-weighted Mendelian randomization (IVW-MR) were used to identify the causal relationship between statins and DR via the use of expression quantitative trait loci (eQTL) data for 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) (31,684 blood samples), low density lipoprotein cholesterol-related GWAS data (sample size: 440,546), and DR-related GWAS data (14,584 cases and 176,010 controls). Additionally, a cross-sectional observational study based on the data from the National Health and Nutrition Examination Survey (NHANES) was conducted to supplement the association between DR and statins (sample size: 106,911). The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) was employed to evaluate the results. Results Based on the results of the MR analysis, HMGCR inhibitors were causally connected with a noticeably greater incidence of DR (IVW: OR = 0.54, 95% CI [0.42, 0.69], p = 0.000002; SMR: OR = 0.66, 95% CI [0.52, 0.84], p = 0.00073). Subgroup analysis revealed that the results were not affected by the severity of DR. The sensitivity analysis revealed the stability and reliability of the MR analysis results. The results from the cross-sectional study based on NHANES also support the association between not taking statins and a decreased risk of DR (OR = 0.54, 95% CI [0.37, 0.79], p = 0.001). Conclusions This study revealed that a significant increase in DR risk was causally related to statins use, providing novel insights into the role of statins in DR. However, further investigations are needed to verify these findings.

Abstract To investigate the sensitivity and potential application of steady-state flash visual evoked potentials (SSFVEP) in assessing the visual function of fundus diseases with vitreous hemorrhage. 18 patients diagnosed with monocular vitreous hemorrhages in the fundus were examined the flash visual evoked potentials (FVEP) and SSFVEP in both eyes. The difference in the P2-wave amplitude of FVEP and the average amplitude of SSFVEP waveform between the diseased eyes and those without vitreous hemorrhage were statistically compared. There was no significant difference in the waveform of FVEP between both eyes. The amplitude of P2-wave from FVEP of the diseased eye was slightly lower than that without vitreous hemorrhage. However, the difference was not statistically significant (P = 0.111). The waveform of SSFVEP in the eye without vitreous hemorrhage showed a towering shape, while that of the diseased eye was flat. The average amplitude of SSFVEP in the diseased eye was statistically lower than that without vitreous hemorrhage (P = 0.036). The difference ratio of SSFVEP amplitude between both eyes was significantly greater than that of FVEP amplitude (P = 0.028). In some fundus diseases with vitreous hemorrhage, SSFVEP had a higher sensitivity than FVEP, providing a novel potential application for visual function assessment.

BackgroundThe Chikungunya virus is an Alphavirus that belongs to the Togaviridae family and is primarily transmitted by mosquitoes. It causes acute infection characterized by fever, headache, and arthralgia. Some patients also experience persistent chronic osteoarthritis-like symptoms. Dedicated antiviral treatments are currently unavailable for CHIKV. This study aims to explore the potential anti-CHIKV effect of rosmarinic acid using network pharmacology.MethodsThis study employed network pharmacology to predict and verify the molecular targets and pathways associated with ROSA in the context of CHIKV. The analysis outcomes were further validated using molecular docking and in vitro experiments.ResultsThe analysis of CHIKV targets using the Kyoto Encyclopedia of Genes and Genomes and MCODE identified IL-17 as an important pathogenic pathway in CHIKV infection. Among the 30 targets of ROSA against CHIKV, nearly half were found to be involved in the IL-17 signaling pathway. This suggests that ROSA may help the host in resisting CHIKV invasion by modulating this pathway. Molecular docking validation results showed that ROSA can stably bind to 10 core targets out of the 30 identified targets. In an in vitro CHIKV infection model developed using 293T cells, treatment with 60 μM ROSA significantly improved the survival rate of infected cells, inhibited 50% CHIKV proliferation after CHIKV infection, and reduced the expression of TNF-α in the IL-17 signaling pathway.ConclusionThis study provides the first confirmation of the efficacy of ROSA in suppressing CHIKV infection through the IL-17 signaling pathway. The findings warrant further investigation to facilitate the development of ROSA as a potential treatment for CHIKV infection.

Objective Our research was performed in order to explore the effects of molecular hydrogen (H2), a novelly-established antioxidant, on the retinal degeneration in rd1 mice, an animal model of inherited retinitis pigmentosa (RP).Methods The rd1 mice were divided randomly into control and H2 intervention groups. Mice from other groups received H2 intervention in three modes, two modes of the hydrogen gas (HG) and one model of hydrogen-rich saline (HRS). At 14 days post born (P14) and P21, various indicators were detected in all mice, including eletroretinogram (ERG), fundus phography, optical coherence tomography (OCT), and retinal immunotaining of microglia cells’ marker, Iba1.Results The ERG amplitude in mice from the control and H2 intervention groups showed no statistical differences (p > 0.05). At P14 and P21, no significant difference in the distance from the retinal pigment epithelium to the outer plexiform layer on OCT from mice of the above two groups was found (p > 0.05). The thickness of the outer nuclear layer (ONL) in mice at P14 and P21 showed no statistical differences between the control group and the H2 intervention group (p > 0.05). In the aspect of the number of Iba1-positive cells, we did not found any significant differences between the two groups (p > 0.05).Conclusion Different forms of H2 intervention (hydrogen-rich saline and hydrogen gas) had no obvious effects on the course of retinal degeneration in rd1 mice. The specific mechanism of photoreceptor degeneration in the hereditary RP mouse model may be different, requiring different medical interventions.

Background & aims: With a drastic increase in the number of chronic hepatitis B (CHB) patients with coexisting nonalcoholic fatty liver disease (NAFLD), there is an urgent need to evaluate antiviral treatment effects in this special population. Methods: CHB patients with hepatic steatosis (CHB + HS) were prospectively recruited with followed-up of 3 years. HS and liver fibrosis were assessed by transient elastography. HS was defined as controlled attenuation parameter (CAP) ≥248 dB/m, and fibrosis progression was defined with ≥1-stage fibrosis increment. Multivariate and propensity score matching (PSM) analysis were used to evaluate antiviral therapy effects on fibrosis progression. Results: In total 212 recruited CHB + HS patients (median age 36 years, median ALT 59 U/L), 49.1% (104/212) received antiviral therapy and 50.9% (108/212) did not. Among patients with antiviral therapy, rates of serum HBV DNA undetectable, HBeAg and HBsAg loss, and ALT normalization at year 3 were 88.5%, 31.0%, 8.7% and 70.2%, respectively. Patients with mild-moderate HS didn't differ patients with severe HS regarding biochemical and virological responses. Antiviral therapy was independently associated with a lower risk of fibrosis progression among the entire cohort (odds ratio 0.473, 95% CI 0.245–0.911, P = 0.025). This finding was further verified by PSM analysis. When stratified by the severity of HS, the antiviral therapy benefits in reducing fibrosis progression were mainly seen in patients with mild-moderate HS. Conclusions: Among CHB + HS patients, long-term antiviral treatment effectively inhibits HBV replication and reduces fibrosis progression. Our findings have implications for the optimal management of this population.

ABSTRACTUpregulation of Sirtuin Type 1 (SIRT1), a nicotinamide adeninedinucleotide (NAD+)-dependent deacetylase, has been proved to protect against ample ocular diseases, while its effect on retinitis pigmentosa (RP) has not been illustrated. The study was aimed to explore the impacts of resveratrol (RSV), a SIRT1 activator, on the photoreceptor degeneration in a rat model of RP induced by N-methyl-N-nitrosourea (MNU), an alkylation. The rats were induced RP phenotypes via the intraperitoneal injection of MNU. The electroretinogram was conducted and revealed that RSV could not prevent the decline of retinal function in the RP rats. The optical coherence tomography (OCT) and the retinal histological examination were performed and showed that the reduced thickness of the outer nuclear layer (ONL) was not preserved by RSV intervention. The immunostaining technique was applied. Afther the MNU administration, the number of the apoptotic photoreceptors in the ONL throughout the retinasand the number of microglia cells present among the outer part throughout the retinas were not significantly reduced by RSV. Western blotting was also performed. The data showed that the level of SIRT1 protein was decreased after MNU administration, while RSV was not able to obviously alleviate the downregulation. Our data together indicated that RSV was not able to rescue the photoreceptor degeneration in the MNU-induced RP rats, which might be due to the MNU-induced consumption of the NAD+.

The Chinese Loess Plateau has undergone extensive revegetation to restore degraded land and enhance carbon sequestration. However, soil organic carbon (SOC) sequestrated in the soil profiles of deep-rooted plants has not been fully studied. Here, we investigated the SOC within a 0–23 m profile in farmlands and apple orchards converted from farmlands with different ages (A5, 20 years) and the controlling factors on three loess tablelands (Changwu, Qingyang, and Luochuan). The results show that SOC stocks among farmlands and orchards showed no significant difference (p = 0.88); however, SOC stocks showed a trend with tree ages, i.e., a decrease for A5 and A10 but an increase for A15 and A20. For the vertical variability, the SOC stock was the highest within 0–1 m, regardless of the standing age; however, the SOC stock in this layer only accounted for 8.8% of the total SOC stock (97.93 ± 9.18 kg m−2). Climate accounted for 82% of the variations and controlled the changes in SOC in the 0–1 m range, while soil texture dominated the SOC in the soil below 1 m, accounting for 57% of the SOC variations. The variations in SOC in the thick, unsaturated zones provide implications for future land use management and the sustainability of apple orchards in arid regions.

Objective: To investigate the feasibility and effectiveness of hydrogen in the treatment of retinitis pigmentosa (RP) patients through the drinking of hydrogen-rich water (HRW). Methods: RP patients clinically diagnosed in our hospital were selected and given HRW for drinking at 400–500 ml twice a day for four consecutive weeks. Changes in best corrected visual acuity (BCVA), intraocular pressure, the retinal thickness, and choroidal thickness, as well as the amplitude and peak time of visual electrophysiological examinations before and after HRW drinking were observed. Data were statistically analyzed. Results: In total, 24 eyes of 13 patients with RP (3 males and 10 females aged–27-65 years old, were enrolled in the study. The BCVA after HRW drinking was 0.34 ± 0.25, which was statistically improved compared with that before (P 0.05). The amplitudes of the b-wave in Dark-adaptation 0.01 response, a and b waves in Dark-adaptation 3.0 response, the Dark-adaptation Ops total wave, a and b waves in Light-adaptation 3.0 response, and the Light-adaptation Flicker response of electroretinogram (ERG) were significantly higher than those before HRW drinking (all P 0.05), while the data from the 15′ PVEP were statistically different (P 0.05). Conclusion: Short-term HRW drinking slightly improved visual function in patients with primary RP, whereas no significant improvement was found in the thickness of the retina and choroid.

Purpose: To assess the effectiveness and safety of combining intravitreal endothelial growth factor inhibitor (anti-VEGF) and ocular corticosteroids for diabetic macular edema (DME). Methods: Articles concentrating on the efficacy and safety of combining anti-VEGF and ocular corticosteroids therapy for DME versus anti-VEGF monotherapy was screened systematically. Meta-analysis was conducted on the basis of a protocol registered in the PROSPERO (CRD42023408338) and performed on the extracted continuous variables and dichotomous variables. The outcome was expressed as weighted mean difference (MD) and risk ratio (RR). Results: Add up to 21 studies including 1468 eyes were enrolled in this study. The MD for best-corrected visual acuity (BCVA) improvement at 1/3/6/12-month between the combination therapy group and monotherapy group were 2.56 (95% CI [0.43, 4.70]), 2.46 (95% CI [−0.40, 5.32]), − 1.76 (95% CI [−3.18, −0.34]), − 1.94 (95% CI [−3.87, 0.00]), respectively. The MD for central retinal thickness (CMT) reduction at 1/3/6/12-month between two groups were − 66.27 (95% CI [−101.08, −31.47]), − 33.62 (95% CI [−57.55, −9.70]), − 4.54 (95% CI [−16.84, 7.76]), − 26.67 (95% CI [−41.52, −11.82]), respectively. Additionally, the combination group had higher relative risk of high intraocular pressure and cataract progression events. Conclusions: Anti-VEGF combined with ocular corticosteroids had a significant advantage over anti-VEGF monotherapy within 3 months of DME treatment, which reached the maximum with increasing anti-VEGF injection times to 3. However, with the prolongation of the treatment cycle, the effect of combined therapy after 6 months was no better than monotherapy, and the side effects of combined therapy were more severe.

Abstract To investigate the prevalence and influencing factors of Demodex folliculorum (DF) in the eyelashes of healthy young males. An epidemiological cross-sectional prevalence study was conducted. We conducted visual acuity, eye-related examination, eyelash microscopic examination and DF count of recruits in Fujian Province in 2019. The presence of DF was analyzed according to age, keratorefractive surgery, annual household income, educational level, long-term residence, sleep time, time of using electronic products, smoking and drinking habit. A total of 2253 healthy young males (aged 17–24 years) were studied for the presence of DF within eyelash follicles. The total prevalence of DF was 20.73% in our study. Subjects with history of keratorefractive surgery had a statistically significant increase in the prevalence of DF (P 0.05). According to the multivariate logistic regression analysis, the history of keratorefractive surgery was the risk factors of DF infection (P 0.05). The prevalence of DF in eyelash follicles in healthy young males was relatively high. The history of keratorefractive surgery was an important risk factor for the infection.

Background: Ferroptosis is a form of iron-dependent regulated cell death, and prior work has highlighted the potential utility of ferroptosis-inducing agents as tools to treat heart failure (HF). To date, however, no detailed examinations of the prognostic utility of ferroptosis-related genes (FRGs) in HF have been conducted. Methods: We used established genomic identification of FRGs for total samples in the gene expression omnibus (GEO) database, screened for differentially expressed FRGs, performed protein-protein interaction analysis and functional analysis of HF immune microenvironment subtypes. Subsequently, we applied tools to calculate immune cell infiltration, compare immune cell, immune response genomic and HLA gene differences between subtypes, and perform candidate drug identification. Finally, preliminary in vivo validation of the screened central genes was performed in animal models. Results: FRGs were compared between samples from HF and healthy control donors, revealing 62 of these genes to be differentially expressed as a function of HF status. HF patient-derived tissues exhibited significant changes in the expression of HLA genes, increase immune cell infiltration, and higher levels of other immune-related genes within the associated immune microenvironment. These FRGs were then leveraged to establish two different immune-related subtypes of HF based on clustering analysis results, after which these subtypes were characterized in further detail. Functional enrichment analyses revealed the identified differentially expressed genes to be enriched in key immune-related pathways including the primary immunodeficiency, natural killer cell-mediated cytotoxicity, FcϵRI signaling, and antigen processing and presentation pathways. The impact of the immune microenvironment was also explored through functional analyses, core gene analyses, and efforts to identify potential drug candidates for HF patients. Moreover, four key hub genes were identified as promising targets for therapeutic intervention in HF, including HDAC1, LNPEP, PSMA1, and PSMA6. Subsequent preclinical work in a mouse model system supported a potential role for HDAC1 as an important biomarker associated with the incidence of HF. Conclusions: To sum up, these results emphasize the importance of ferroptosis as a regulator of the HF-related immune microenvironment, highlighting viable avenues for the further study of molecular targets amenable to pharmacological intervention with the aim of treating this debilitating disease.

Applying biochar to soil has been advocated as an effective measure to improve soil fertility and increase carbon (C) sequestration. Biochar is often co-applied with nitrogen (N) fertilizers in agricultural ecosystems, however, the interactive effects of biochar and N addition (BN) on soil greenhouse gases (GHGs) fluxes, soil C and N fractions, and yield has not been investigated. Here, we manipulated a global meta-analysis to explore the effects of biochar and N addition and their interaction on the GHGs, soil C and N fractions, and yield by assembling 75 articles. Results indicate that across all studies, biochar, N, and BN additions all increased soil CO2 emissions (8.5%–29.6%), yield (4.2%–58.2%), soil organic C (SOC, 1.8%–50.4%), dissolved organic C (DOC, 2.7%–30.0%), and total N (TN, 6.8%–15.6%), but had no significant effect on CH4 fluxes. Biochar addition reduced N2O emissions (−21.3%), global warming potential (GWP, −19.8%), greenhouse gas intensity (GHGI, −28.2%), NH4+ (−17.8%) and NO3− (−10.7%), whereas N addition increased these indexes. The interaction effects of BN on CO2 and N2O emissions, GWP, TN, and NH4+ contents were antagonistic, while CH4 emissions, DOC, MBC, NO3−, and yield exhibited synergistic responses. Notably, soil GHGs responses varied depending on geo-climatic factors, edaphic properties, biochar and N treatment parameters, and experimental scenarios. These findings indicate that the co-addition of biochar and N has the potential to mitigate climate change and improve yield, providing a valuable reference for the improvement of climate-smart agriculture.

Abstract Microorganisms of the soil‐root continuum play key roles in ecosystem function. The Loess Plateau is well known for its severe soil erosion and thick loess worldwide, where mean annual precipitation (MAP) and soil nutrients decrease from the southeast to the northwest. However, the relative influence of environmental factors on the microbial community in four microhabitats (bulk soil, rhizosphere, rhizoplane, and endosphere) in the soil‐root continuum along the environmental gradient in the Loess Plateau remains unclear. In this study, we investigated 82 field sites from warm‐temperate to desert grasslands across the Loess Plateau, China, to assess the bacterial diversity, composition, community assembly, and co‐occurrence networks in the soil‐root continuum along an environmental gradient using bacterial 16S recombinant DNA amplicon sequencing. We discovered that the microhabitats explained the largest source of variations in the bacterial diversity and community composition in this region. Environmental factors (e.g., MAP, soil organic carbon, and pH) impacted the soil, rhizosphere, and rhizoplane bacterial communities, but their effects on the bacterial community decreased with increased proximity to roots from the soil to the rhizoplane, and the MAP enlarged the dissimilarity of microbial communities from the rhizosphere and rhizoplane to bulk soil. Additionally, stochastic assembly processes drove the endosphere communities, whereas the soil, rhizosphere, and rhizoplane communities were governed primarily by the variable selection of deterministic processes, which showed increased importance from warm‐temperate to desert grasslands. Moreover, the properties of the microbial networks in the rhizoplane community indicate more stable networks in desert grasslands, likely conferring the resistance of microbial communities in higher stress environments. Collectively, our results showed that the bacterial communities in the soil‐root continuum had different sensitivities and assembly mechanisms along an environmental gradient. These patterns are shaped simultaneously by the intertwined dimensions of proximity to roots and environmental stress change in the Loess Plateau.

This case report describes the detailed electrophysiological features and the corresponding relationship with the structural changes in a case of X-linked juvenile retinoschisis (XLRS). A 25-year-old male presented with a history of several years of decreased visual acuity in both eyes. The best corrected visual acuity was 20/200 in oculus dexter (OD) and 20/80 in oculus sinister. Retinoschisis was found in the macula by optical coherence tomography, which was more severe in OD. Electroretinogram revealed a similar electronegative waveform in both eyes. Visual evoked potential detected a reduced amplitude and delayed phase in P100-wave, which was worse in OD. The patient was diagnosed as XLRS and advised to undergo continuous medical observation. He was followed up for the next year, with no significant change in retinal function and structure being observed. These current findings suggest that electrophysiology permits the detailed analysis of the clinical picture of XLRS and helps to gain a deeper understanding of the pathogenesis.

The complicated driving force at the stress corrosion cracking (SCC) tip of the safe-end dissimilar metal-welded joints (DMWJs) in the pressurized water reactor (PWR) is mainly caused by the heterogeneous material mechanical properties. In this research, to accurately evaluate the crack driving force at the SCC in DMWJs, the stress-strain condition, stress triaxiality, and J-integral of the crack tip at different positions are analyzed based on the heterogeneous material properties model. The results indicate that the larger driving force will be provided for the I-type crack when the crack is in the SA508 zone and the interface between the 316L region and base metal. In addition, the heterogeneous material properties inhibit the J-integral of the crack in the 316L region, which has a promoting effect when the crack is in the SA508 zone and weld metal. It provides a new idea for analyzing driving force at the crack tip and safety evaluation of DMWJs in PWRs.

Abstract Background Coronavirus disease 2019 (COVID-19) is a newly emerging infectious disease and rapidly escalating epidemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The pathogenesis of COVID-19 remains to be elucidated. We aimed to clarify correlation of systemic inflammation with disease severity and outcomes in COVID-19 patients. Methods In this retrospective study, baseline characteristics, laboratory findings, and treatments were compared among 317 laboratory-confirmed COVID-19 patients with moderate, severe, or critically ill form of the disease. Moreover, the longitudinal changes of serum cytokines, lactate dehydrogenase (LDH), high-sensitivity C-reactive protein (hsCRP), and hsCRP to lymphocyte count ratio (hsCRP/L) as well as their associations with disease severity and outcomes were investigated in 68 COVID-19 patients. Results Within 24 h of admission, the critically ill patients showed higher concentrations of inflammatory markers including serum soluble interleukin (IL)-2 receptor, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), ferritin, procalcitonin, LDH, hsCRP, and hsCRP/L than patients with severe or moderate disease. The severe cases displayed the similar response patterns when compared with moderate cases. The longitudinal assays showed the levels of pro-inflammatory cytokines, LDH, hsCRP, and hsCRP/L gradually declined within 10 days post admission in moderate, severe cases or those who survived. However, there was no significant reduction in cytokines, LDH, hsCRP, and hsCRP/L levels in critically ill or deceased patients throughout the course of illness. Compared with female patients, male cases showed higher serum concentrations of soluble IL-2R, IL-6, ferritin, procalcitonin, LDH, and hsCRP. Multivariate logistic regression analysis revealed that IL-6 > 50 pg/mL and LDH > 400 U/L on admission were independently associated with disease severity in patients with COVID-19. Conclusion Exuberant inflammatory responses within 24 h of admission in patients with COVID-19 may correlate with disease severity. SARS-CoV-2 infection appears to elicit a sex-based differential immune response. IL-6 and LDH were independent predictive parameters for assessing the severity of COVID-19. An early decline of these inflammation markers may be associated with better outcomes.

Abstract Background Retinitis pigmentosa (RP) is a kind of inherited retinal degenerative diseases characterized by the progressive loss of photoreceptors. RP has been a conundrum without satisfactory countermeasures in clinic until now. Acetaldehyde dehydrogenase 2 (ALDH2), a major enzyme involved in aldehyde detoxification, has been demonstrated to be beneficial for a growing number of human diseases, such as cardiovascular dysfunction, diabetes mellitus and neurodegeneration. However, its protective effect against RP remains unknown. Our study explored the impact of ALDH2 on retinal function and structure in N-methyl-N-nitrosourea (MNU)-induced RP rats. Methods Rats were gavaged with 5 mg/kg Alda-1, an ALDH2 agonist, 5 days before and 3 days after MNU administration. Assessments of retinal function and morphology as well as measurement of specific proteins expression level were conducted. Results Electroretinogram recordings showed that Alda-1 administration alleviated the decrease in amplitude caused by MNU, rendering protection of retinal function. Mitigation of photoreceptor degeneration in MNU-treated retinas was observed by optical coherence tomography and retinal histological examination. In addition, Western blotting results revealed that ALDH2 protein expression level was upregulatedwith increased expression of SIRT1 protein after the Alda-1 intervention. Besides, endoplasmic reticulum stress (ERS) was reduced according to the significant downregulation of GRP78 protein, while apoptosis was ameliorated as shown by the decreased expression of PARP1 protein. Conclusions Together, our data demonstrated that ALDH2 could provide preservation of retinal function and morphology against MNU-induced RP, with the underlying mechanism at least partly related to the modulation of SIRT1, ERS and apoptosis.

The etiology of diarrhea-predominant irritable bowel syndrome (IBS-D) is complicated and closely related to neurotransmission in the gastrointestinal (GI) tract. Developing new strategies for treating this disease is a major challenge for IBS-D research. Berberine hydrochloride (BBH), the derivative of berberine, is a herbal constituent used to treat IBS. Previous studies have shown that BBH has potential anti-inflammatory, antibacterial, analgesic, and antidiarrheal effects and a wide range of biological activities, especially in regulating the release of some neurotransmitters. A modified IBS-D rat model induced by chronic restraint stress was used in all experiments to study the effects of BBH on the GI tract. This study measured the abdominal withdrawal reflex (AWR) response to graded colorectal distention (CRD; 20, 40, 60, and 80 mmHg) and observed the fecal areas of stress-induced IBS-D model. Experiments were conducted using organ bath techniques, which were performed in vitro using strips of colonic longitudinal smooth muscle. Inhibitory and excitatory neurotransmitter agents were added to each organ bath to observe contractile responses on the strips and the treatment effect exerted by BBH. The IBS-D rat model was successfully induced by chronic restraint stress, which resulted in an increased defecation frequency and visceral hypersensitivity similar to that of humans. BBH could reduce 4-h fecal areas and AWR response to CRD in IBS-D. The stress-induced IBS-D model showed upregulated colonic mRNA expression levels of 5-hydroxytryptamine-3A receptor and downregulated expression levels of neuronal nitric oxide synthase. Meanwhile, BBH could reverse this outcome. The responses of substances that regulate the contraction induced by related neurotransmission in the longitudinal smooth muscle of IBS-D colon (including the agonist of acetylcholine, carbachol; NOS inhibitor, L-NAME; and P2Y1 receptor antagonist, MRS2500) can be inhibited by BBH. In summary, BBH promotes defecation frequency and visceral hypersensitivity in IBS-D and exerts inhibitory effects on contractile responses in colonic longitudinal smooth muscle. Thus, BBH may represent a new therapeutic approach for treating IBS-D.

Abstract Background Oxidative stress (OS) is an essential factor in the pathogenesis of branch retinal vein occlusion (BRVO). Studies have demonstrated the role of hydrogen gas in the regulation of OS. This study was designed to evaluate the efficacy of hydrogen gas on the BRVO rat model. Methods Twenty-four BRVO rats were randomly divided into two groups: the hydrogen gas (H) group (42% H2, 21% O2, 37% N2) and the model (M) group (21% O2, 79% N2). Rats in the H group inhaled hydrogen gas for 8 h every day up to 30 d post-occlusion. Twelve age-matched healthy rats served as the control (C) group. Retinal function and morphology were detected at 1, 7, 14 and 30 d post-occlusion. Furthermore, the expression of vascular endothelial growth factor (VEGF-α) was detected by immunofluorescent staining. Results Full-field electroretinography (ffERG) revealed that the amplitude of the b-wave (dark-adaptation 3.0 response), the amplitude of the OPs2 wave and the light-adapted flicker response in the H group were all higher than those in the M group at 7 d post-occlusion (all p 0.05). Conclusions Our findings demonstrate that inhalation of hydrogen gas could alleviate retinal oedema, shorten reopen time and improve retinal function, and the potential mechanism might be related to a decrease in VEGF-α expression.

Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: NCT04365634.ContextDiabetes mellitus was associated with increased severity and mortality of disease in COVID-19 pneumonia. So far the effect of type 2 diabetes (T2DM) or hyperglycemia on the immune system among COVID-19 disease has remained unclear.ObjectiveWe aim to explore the clinical and immunological features of type 2 diabetes mellitus (T2DM) among COVID-19 patients.Design and MethodsIn this retrospective study, the clinical and immunological characteristics of 306 hospitalized confirmed COVID-19 patients (including 129 diabetic and 177 non-diabetic patients) were analyzed. The serum concentrations of laboratory parameters including cytokines and numbers of immune cells were measured and compared between diabetic and non-diabetic groups.ResultsCompared with non-diabetic group, diabetic cases more frequently had lymphopenia and hyperglycemia, with higher levels of urea nitrogen, myoglobin, D-dimer and ferritin. Diabetic cases indicated the obviously elevated mortality and the higher levels of cytokines IL‐2R, IL‐6, IL‐8, IL‐10, and TNF‐α, as well as the distinctly reduced Th1/Th2 cytokines ratios compared with non-diabetic cases. The longitudinal assays showed that compared to that at week 1, the levels of IL-6 and IL-8 were significantly elevated at week 2 after admission in non-survivors of diabetic cases, whereas there were greatly reductions from week 1 to week 2 in survivors of diabetic cases. Compared with survival diabetic patients, non-survival diabetic cases displayed distinct higher serum concentrations of IL-2R, IL-6, IL-8, IL-10, TNF‐α, and lower Th1/Th2 cytokines ratios at week 2. Samples from a subset of participants were evaluated by flow cytometry for the immune cells. The counts of peripheral total T lymphocytes, CD4+ T cells, CD8+ T cells and NK cells were markedly lower in diabetic cases than in non-diabetic cases. The non-survivors showed the markedly declined counts of CD8+ T cells and NK cells than survivors.ConclusionThe elevated cytokines, imbalance of Th1/Th2 cytokines ratios and reduced of peripheral numbers of CD8+ T cells and NK cells might contribute to the pathogenic mechanisms of high mortality of COVID-19 patients with T2DM.

This report describes a patient who had acute lymphocytic leukemia with exudative retinal detachment (RD), which mimicked Vogt–Koyanagi–Harada disease (VKH). A 61-year-old woman presented with painless loss of vision in the left eye. Fundus examination revealed RD in her left eye. B-scan ultrasonography confirmed localized RD and choroidal thickening. Fundus fluorescein angiography revealed stippled pinpoint hyperfluorescence in the upper macula. One week later, reduced visual acuity was noted in the right eye. B-scan ultrasonography and optical coherence tomography revealed serous RD in both eyes. A provisional diagnosis of VKH was made. However, subsequent hematologic analysis detected an extremely high leukocyte count. Elevated numbers of leukocytes and tumor cells were found in cerebrospinal fluid. Bone marrow biopsy revealed 77% primary atypical blood cells, 89% of which were immature lymphocytes. The patient was subsequently diagnosed with acute lymphocytic leukemia and transferred to the Department of Hematology. However, the patient and her family refused chemotherapy; she eventually died. Our findings suggest that exudative RD, similar to VKH, could be a sign of leukemia. Pinpoint hyperfluorescence leakage is important for differential diagnosis, particularly with respect to VKH.

A double-layer tuned mass damper (DTMD) has advantages of wide damping frequency band and strong robustness. At present, there is a lack of seismic design methods for high-rise structures based on DTMDs. In this study, a DTMD parameter optimisation method was proposed, with the objective of minimising the peak displacement response of a first N-order vibration modal with a vibration mass participation factor of 85%. Then, a scale model of a high-rise structure was fabricated, along with a corresponding DTMD. Different types of excitations were chosen to clarify the dynamic responses of the model with and without the DTMD, including Site-II ground motions, long-period (LP) ground motions without pulses, and near-fault pulse-type (NFPT) ground motions. The results indicate that the dynamic responses of high-rise structures under LP and NFPT ground motions are much greater than those under Site-II ground motions. The DTMD can effectively reduce the absolute displacement response, acceleration response, and strain response at the top floor of the test model. However, the DTMD has a time delay in providing the damping effect. A smaller damping ratio between the upper TMD and the controlled structure will lead to a more significant damping effect for the DTMD.

Background/Aims: Our laboratory discovered a Kunming mouse with enormous electroretinogram (ERG) defects. Its auditory brainstem response (ABR) threshold was significantly elevated and closely resembled the features of Usher syndrome (USH). This study sought to cross these USH-like mice (named KMush/ush mice) with CBA/CaJ mice to establish recombinant inbred strains and identify their phenotypes and genotypes. Methods: KMush/ush mice were crossed with CBA/CaJ mice to establish inbred strains by sibling mating. ERG, ABR, ocular fundus morphology, histological examinations of the retina and inner ear, quantitative real-time polymerase chain reaction, western blotting, and exon sequencing were performed to assess the phenotypes and genotypes of the offspring strains. Results: The F1 hybrids from crossing KMush/ush and CBA/CaJ mice had normal ERG and ABR responses. The F2 offspring from intercrossing the F1 mice showed a segregation of the retinitis pigmentosa (RP) and hearing loss phenotypes. The CBA-1ush/ush mice had an RP phenotype that was characterized by a vanished ERG waveform and loss of the outer nuclear layer. Their Pde6b gene had a nonsense mutation that resulted in the failure of protein production in western blotting. However, the ABR threshold of this strain of mice was normal. The CBA-2ush/ush mice had normal retinal function and architecture. Their ABR threshold was increased, with a dramatic degeneration of the stereocilia bundles in the outer hair cells of the inner ear. Whole exome sequencing and exon sequencing revealed a deletion of one base pair in exon 31 of the Adgrv1 gene, which would result in the premature termination of protein encoding. The level of Adgrv1 mRNA was reduced in the CBA-2ush/ush mice. The CBA-3ush/ush mice had phenotypes of RP, elevated ABR threshold, and degeneration of the stereocilia bundles in the outer hair cells. They were closely associated with the nonsense mutations of Pde6b and Adgrv1, respectively. Conclusion: We isolated a mouse strain with hearing loss from inbred mice with retinal degeneration and established it as a recombinant inbred strain with a spontaneous mutation in Adgrv1, the human Usher syndrome 2C gene. The retinal degeneration was cause by a mutation in Pde6b, while the hearing loss was caused by a mutation in Adgrv1.

Macrophage differentiation and inflammatory function are controlled by cell metabolism. Here, the authors use a viral hepatitis model and a high-fat diet model of insulin resistance to show how VSIG4 inhibits inflammatory macrophage activation by modulating mitochondrial pyruvate metabolism.

Abstract Leaf gas exchange is closely associated with water relations; however, less attention has been given to this relationship over successive drought events. Dynamic changes in gas exchange and water potential in the seedlings of two woody species, Amorpha fruticosa and Robinia pseudoacacia, were monitored during recurrent drought. The pre-dawn leaf water potential declined in parallel with gas exchange in both species, and sharp declines in gas exchange occurred with decreasing water potential. A significant correlation between pre-dawn water potential and gas exchange was observed in both species and showed a right shift in R. pseudoacacia in the second drought. The results suggested that stomatal closure in early drought was mediated mainly by elevated foliar abscisic acid (ABA) in R. pseudoacacia, while a shift from ABA-regulated to leaf-water-potential-driven stomatal closure was observed in A. fruticosa. After re-watering, the pre-dawn water potential recovered quickly, whereas stomatal conductance did not fully recover from drought in R. pseudoacacia, which affected the ability to tightly control transpiration post-drought. The dynamics of recovery from drought suggest that stomatal behavior post-drought may be restricted mainly by hydraulic factors, but non-hydraulic factors may also be involved in R. pseudoacacia.

We previously showed that potassium channel tetramerization domain containing 9 (KCTD9) is aberrantly expressed in natural killer (NK) cells in patients with hepatitis B virus-associated acute-on-chronic liver failure and mice with experimental fulminant hepatitis. However, the mechanism underlying the regulation of NK cell function and fulminant hepatitis progression by KCTD9 is unknown. Here, we investigated the role of Kctd9 in regulation of early development, maturation, and function of NK cells using Kctd9-knockout mice. Compared to wild-type mice, Kctd9-deficient mice exhibited impaired NK cell lineage commitment, as evidenced by selective reduction in the refined NK progenitors, and incomplete NK cell maturation, as manifested by a higher proportion of CD11b− NK cells and a lower percentage of CD11b+ NK cells with high proliferative potential. Moreover, Kctd9-depleted NK cells displayed insufficient IFN-γ production, degranulation, and granzyme B production in response to cytokine stimulation, and attenuated cytotoxicity to tumor cells in vitro. The defect in NK cells was further supported by ameliorated liver damage and improved survival in Kctd9-deficient mice following murine hepatitis virus strain-3 (MHV-3) infection, which otherwise leads to immune-mediated fulminant hepatitis, a phenotype homologous to that caused by NK cell depletion in wild-type mice. Further investigation to identify the underlying mechanism revealed that Kctd9 deficiency hindered the expression of transcription factors, including Ets1, Nfil3, Eomes, and Id2 in NK cells. Collectively, our data reveal that Kctd9 acts as a novel regulator for NK cell commitment, maturation, and effector function.

Branch retinal vein occlusion (BRVO) is a common retinal vascular disorder leading to visual impairment. Currently, the general strategies for BRVO are symptomatic therapies. Cardiovascular aspects are essential risk factors for BRVO. The traditional Chinese medicine hexuemingmu (HXMM), consisting of tanshinol and baicalin, dilates the vasculature and accelerates microcirculation. Therefore, the aim of this study was to determine the efficacy and possible mechanism of HXMM in a BRVO rat model established by laser photocoagulation. Successful BRVO rat models were treated with different doses of HXMM. Fundus photography and fluorescein fundus angiography (FFA) of the animals were applied. The retinal layers were measured by optical coherence tomography (OCT). Full-field electroretinography (ffERG) was applied to evaluate the retinal function. The ear vein flow velocity was measured via a microcirculation detector. The expression of the vascular endothelial growth factor (VEGF-α) was measured via western blotting and immunofluorescent staining. Our study found that retinal edema predominantly occurred in the inner nuclear layer (INL) and outer nuclear layer (ONL). The retinal edema of the treated groups was significantly relieved in the early stage of BRVO as visualized via OCT detection and HE staining. The amplitudes of the b wave and oscillatory potentials (OPs) waves of ffERG in the treated groups were increased compared with those of the control group at several detection points (3, 5, 7, 10, 14, and 21 d postocclusion). The expression of VEGF-α was reduced in the treated groups at an early stage of BRVO. Furthermore, the ear vein flow velocity of the HXMM treatment groups was faster than that of the control group. Thus, our study indicates that the traditional Chinese medicine HXMM could ameliorate retinal edema and rescue the retinal structure and function in BRVO models through promoting occluded vein recanalization, improving microcirculation, and regulating the expression of VEGF-α.

Background: Fulminant hepatitis (FH) is a serious threat to human life, accompanied by massive and rapid necroinflammation. Kupffer cells, the major immune cell population involved in innate immune responses, are considered to be central for FH. Fibrinogen-like protein 2 (Fgl2) is a pro-coagulant protein that is substantially induced in macrophages upon viral infection, and Fgl2 depletion represses murine hepatitis virus strain 3 (MHV-3) infection. Clara cell 10 kDa (CC10) protein is a secretory protein with anti-inflammatory properties in allergic rhinitis and asthma. However, its mechanisms of action and pathogenic roles in other disease are still unclear. In this study, we aimed to determine the role of CC10 in FH and the regulation of Fgl2 by CC10.Methods: A mouse FH model was established by peritoneal injection of MHV-3. The mice received CC10 protein through tail vein injection before viral infection. Survival rate, liver function, liver histology, fibrin deposition, and necrosis were examined. The regulatory effect of CC10 on Fgl2 expression was investigated using THP-1 cells and mouse peritoneal macrophages in vitro.Results: In the mouse FH model induced by MHV-3, the survival rate increased from 0 to 12.5% in the CC10 group compared to that in the saline-only control group. Meanwhile, the levels of ALT and AST in serum were significantly decreased and liver damage was reduced. Furthermore, hepatic Fgl2, TNF-α, and IL-1β expression was obviously downregulated together with fibrin deposition, and hepatocyte apoptosis was reduced after administration of CC10 protein. In vitro, CC10 was found to significantly inhibit the expression of Fgl2 in IFN-γ-treated THP-1 cells and MHV-3-infected mouse peritoneal macrophages by western blot and real-time PCR. However, there was no direct interaction between CC10 and Fgl2 as shown by co-immunoprecipitation. Microarray investigations suggested that HMG-box transcription factor 1 (HBP1) was significantly low in CC10-treated and IFN-γ-primed THP-1 cells. HBP1-siRNA treatment abrogated the inhibitory effect of CC10 on Fgl2 expression in Human Umbilical Vein Endothelial cells (HUVECs).Conclusion:CC10 protects against MHV-3-induced FH via suppression of Fgl2 expression in macrophages. Such effects may be mediated by the transcription factor HBP1.

Soil water has become a major limiting factor in agriculture and forestry development on the Loess Plateau of China. In the past 20–30 years, large areas of apple orchards have been built in this region, which have resulted in excessive consumption of deep soil water and soil desiccation. To evaluate the effects of orchard development on deep soil water content (SWC), a meta-analysis of 162 sampling sites on the loess tableland from 44 peer-reviewed publications was conducted in this study. The results showed that the deep SWC in orchards depended on stand age, planting density and annual precipitation. In regions with 550–600 mm precipitation, the orchard with lower planting density showed no soil desiccation in young and early fruiting stages, while deep soil (>2 m) desiccation occurred in full fruiting and old orchards. The effect of planting density on deep SWC varied with stand age. There were significant differences in SWC among different planting densities in early fruiting orchards (p < 0.05), in which soil desiccation occurred in orchards with higher planting density. However, with the continuous consumption of soil water by apple trees, deep soil desiccation occurred in old orchards regardless of planting density. Further, affected by the spatial variation of annual precipitation, deep SWC in orchards significantly decreased with annual precipitation from 650 to 500 mm among the 44 study sites (p < 0.05). Our results suggest that the planting density should be reasonably regulated on the level of annual precipitation, and apple trees need to be pruned appropriately with a goal of moderate productivity, so as to achieve the sustainable use of regional water resources, food security and economic development.

To obtain an accurate uniform hazard spectrum (UHS), this paper proposes combining a stochastic simulation with probabilistic seismic hazard analysis. The stochastic method fully accounts for the effect of the source mechanism, path, and site effect. Historical ground motions in the site specific to the nuclear power plant (NPP) are simulated, and a UHS with an equal exceeding probability is proposed. To compare the seismic performance of the NPP under different ground motions generated by the existing site spectrum (SL-2), the UHS generated by the safety evaluation report, and the US RG1.60 spectrum, respectively, a three-dimensional finite element model is established, and dynamic analysis is performed. Results show that the structural responses to different spectra varied; the UHS response was slightly larger than that of RG1.60. This finding is relatively more reasonable than prior research results. The UHS generated using the stochastic simulation method can provide a reference for the seismic design of NPPs.

The paper presents experimental study on an improved plate lead shear damper with long stroke (ILSD-LS) which is developed to meet the engineering requirements for high-rise structures with long periods subjected to the long-period earthquakes. Finite element analysis is also carried out to investigate the proposed damper. Based on the ideal rigid-plastic constitutive law of lead, a mechanical model of the ILSD-LS is established. Compared with ordinary dampers, ILSD-LS has better damping force, energy dissipation capacity, and stability according to the results of simulation and experiments. The method of calculating damping force is reasonable and accurate. In order to verify the damping effect of ILSD-LS for the structures with long periods under long-period ground motions, the nonlinear time history analysis of a typical high-rise structure with ILSD-LS is carried out. The numerical results indicate that the seismic responses of the high-rise structure with ILSD-LS are significantly reduced when subjected to long-period ground motion.

In order to establish accurate compressive constitutive model of Hybrid Fiber-Reinforced Concrete (HFRC), 10 groups of HFRC specimens containing polyvinyl alcohol (PVA), polypropylene (PP), and steel fibers are designed and compressive testing is conducted. On the basis of summarizing and comparing the existing research, accuracy of various stress-strain constitutive model is compared and the method of calculating fitting parameters is put forward, peak stress, peak strain, and elastic modulus of specimens with different fiber proportion are analyzed, the calculation expressions of each fitting parameter are given. The results show that, under the condition that the volume of the hybrid fiber is 2% with the proportion of the steel fiber increase, the strength of the specimen increases, the peak strain decreases slightly, and the elastic modulus increases significantly. In specimens mixed with PVA-PP hybrid fiber, with the increase of PVA fiber proportion, the peak stress and elastic modulus of the material are improved, and the peak strain are decreased. The existing stress-strain expressions agree well with the tests. Accuracy of exponential model proposed in this paper is the highest, which can be applied in engineering and nonlinear finite element analysis of components.

A curved bridge test model with a scale ratio of 1:10 was constructed to investigate the influence of site conditions on curved bridges with longitudinal slopes based on a similar theory. The natural ground motions of five different groups, namely, Sites A⁻E, were selected from the Pacific Earthquake Engineering Center (PEER) seismic database, and the shaking table model test was conducted under horizontal unidirectional and bidirectional excitations. Results showed that the structural response of the curved bridge is sensitive to the ground motion of different site conditions. Spatial characteristics are observed in the main girder structural response of the curved bridge. When the curved bridge is parallel to the direction of the principal ground motion, the rotation effect of the main girder is greater than that perpendicular to the direction of the principal ground motion. The rotation effect of the main girder leads to evident beam end and bearing displacements at the low pier. The seismic excitation direction and pier height notably affect the displacement response of the pier, and the tangential displacement response of the fixed pier is sensitive to seismic excitation.

The tableland-gully region is one of the main topographic-ecological units in the Chinese Loess Plateau (CLP), and the soil in this region suffers from serious water erosion. In recent years, much work has been conducted to control soil erosion in this area. This paper summarized the development of soil and water conservation researches in the CLP from the bibliometric perspective based on the Science Citation Index (SCI) and Chinese National Knowledge Infrastructure (CNKI) databases. The quantity of SCI literatures has increased rapidly since 2007, with an average annual growth rate of 21.4%, and the quantity of CNKI literatures in the last decade accounted for 62% of the past 30 years. The development trends showed that early SCI research was related to loess geology in the context of ecological remediation, while the CNKI literature focused on agricultural production under comprehensive management. Over time, the research themes of the two databases gradually became unified, i.e., the management of sloping farmland and the improvement of agricultural productivity. Subsequently, the themes gradually extended to the disposition of comprehensive control measures for soil erosion and the environmental effect of agro-fruit ecosystems. The highly cited papers mainly focused on soil reservoir reconstruction, soil erosion factors, and environmental effects of vegetation restoration. Two aspects need further study, including (i) the effect of soil erosion control under different ecological remediation patterns; and, (ii) the ecosystem maintenance mechanism and regulation approaches that are based on the sustainable utilization of soil and water resources in the tableland-gully region of the Loess Plateau.

Moving load identification is an important part of bridge structure health monitoring; accurate and reliable load data can be used to check the load of bridge design, and the load spectrum can provide a more practical basis for structural fatigue analysis. The method of the BP neural network is used in bridge moving loads identification. The numerical examples of identification of the axle loads of a two-axle vehicle moving on a simply supported bridge under various speeds and weights are carried out. The sensitivity of the bridge deflection and strain to moving loads is analyzed, and the influences of different activation function combinations and algorithm on network are discussed. The identification results of different load conditions are analyzed and the effect of noise is considered. Finally the rationality of the method is verified by experiments. It is shown that the indirect estimation of vehicle weight by BP neural network from dynamic responses is feasible.

Oxidative stress (OS) and endoplasmic reticulum stress (ERS) are the major factors underlying photoreceptor degeneration. Lutein, RR-zeaxanthin (3R,3’R-zeaxanthin) and RS (meso)-zeaxanthin (3R,3’S-RS- zeaxanthin) (L/Zi) could protect against cell damage by ameliorating OS in retina. In this study, we examined the effect of L/Zi supplementation in a mouse model of photoreceptor degeneration and investigated whether the treatment of L/Zi ameliorated OS and ERS. BALB/cJ mice after light exposure were used as the animal model. The protective effects of L/Zi were observed by electroretinography (ERG) and terminal deoxyuridine triphosphate nick-end labeling (TUNEL) analysis. The underlying mechanisms related to OS and ERS were explored by Western blotting. After L/Zi treatment, the ERG amplitudes were significantly higher, and the number of TUNEL-positive cells was significantly reduced compared to that of the vehicle group. Western blotting results revealed that OS was ameliorated according to the significant downregulation of phosphorylated c-Jun N-terminal kinase (p-JNK), and significant upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2). In addition, ERS was reduced according to the significant downregulation of 78 kDa glucose-regulated protein (GRP78), phosphorylated protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), activating transcription factor 4 (ATF4) and activating transcription factor (ATF6). Our data shows that L/Zi provided functional and morphological preservation of photoreceptors against light damage, which is probably related to its mitigation of oxidative and endoplasmic reticulum stress.

Viral fulminant hepatitis (FH) is a severe disease with high mortality resulting from excessive inflammation in the infected liver. Clinical interventions have been inefficient due to the lack of knowledge for inflammatory pathogenesis in the virus-infected liver. We show that wild-type mice infected with murine hepatitis virus strain-3 (MHV-3), a model for viral FH, manifest with severe disease and high mortality in association with a significant elevation in IL-1β expression in the serum and liver. Whereas, the viral infection in IL-1β receptor-I deficient (IL-1R1-/-) or IL-1R antagonist (IL-1Ra) treated mice, show reductions in virus replication, disease progress and mortality. IL-1R1 deficiency appears to debilitate the virus-induced fibrinogen-like protein-2 (FGL2) production in macrophages and CD45+Gr-1high neutrophil infiltration in the liver. The quick release of reactive oxygen species (ROS) by the infected macrophages suggests a plausible viral initiation of NLRP3 inflammasome activation. Further experiments show that mice deficient of p47phox, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit that controls acute ROS production, present with reductions in NLRP3 inflammasome activation and subsequent IL-1β secretion during viral infection, which appears to be responsible for acquiring resilience to viral FH. Moreover, viral infected animals in deficiencies of NLRP3 and Caspase-1, two essential components of the inflammasome complex, also have reduced IL-1β induction along with ameliorated hepatitis. Our results demonstrate that the ROS/NLRP3/IL-1β axis institutes an essential signaling pathway, which is over activated and directly causes the severe liver disease during viral infection, which sheds light on development of efficient treatments for human viral FH and other severe inflammatory diseases.

A dry soil layer (DSL) is a common soil desiccation phenomenon that generally forms at a particular depth in the soil profile because of climatic factors and poor land management, and this phenomenon can influence the water cycle and has been observed on the Loess Plateau of China and other similar regions around the world. Therefore, an investigation of the DSL formation depth (DSLFD), thickness (DSLT) and mean water content (MWDSL) on the Loess Plateau can provide valuable information. This paper synthesized 69 recent publications (1,149 observations of DSLs from 73 sites) that focused on DSLs in this region, and the results indicated that DSLs are significantly affected by climatic and vegetation factors. The mean annual precipitation had a significant positive relationship with DSLFD (p = 0.0003) and MWDSL (p

The significance of information fusion for structural health monitoring and damage detection is introduced. The three levels of information fusion for multisensors are described. For the complex in the structural health monitoring, the distributed multisensor information fusion is more suitable and the structure is discussed. In the damage information fusion for character level, the concept for structural integral support vector machine damage detection matrix, damage self-information, and damage information entropy are presented. For a complex structure, it can be divided into multiple substructures in order to simplify the difficult for health monitoring, the data acquisition and support vector machine are established for each substructure in order to form integral damage detection matrix. In the damage information fusion for decision level, the methods based on fuzzy set theory, material element theory, and fuzzy neural network are proposed. The results given by a numerical example about space structure show that all the methods are valid and effective.