Self-heating mitochondrion-induced free radical blast for immunogenic cell death stimulation and HCC immunotherapy.

Hepatocellular carcinoma (HCC) is an immunosuppressive tumor associated with high mortality. Photothermal and photodynamic therapies have been applied to induce immunogenic cell death (ICD) in HCC, successfully eliciting immune responses but facing limitations in penetration depth in clinical trials. Here, intrinsic mitochondrial hyperthermia was used to trigger thermosensitive drug release. The mitochondria were further self-heated through 2,4-dinitrophenol uncoupling, dramatically promoting free radical initiation and inducing tumor ICD. The synthesized mitochondrial-targeting TPP-HA-TDV nanoparticles specifically generated free radicals in the mitochondria without external stimulation, and obviously enhanced the release of ICD markers, subsequently evoking immune responses. The results showed that mitochondrial hyperthermia could be an endogenous target for thermosensitive drug release. Furthermore, self-heating mitochondria-induced free radical blast could be an efficient therapeutic for deep-seated tumor therapy.

Crop effect and mechanism of amino acid-modified biomass ash in remediation of cadmium-contaminated soil.

Lignocellulosic biomass ash (BA) has certain adsorption and passivation effects on heavy metals, but its function is generally weak. Amino acid salt can facilitate the leaching of heavy metals in soil. Therefore, modification of BA with amino acid salt may realize a higher leaching rate and better passivation of heavy metals in soil. In this study, BA was modified by amino acid hydrolysate obtained from the hydrolysis of chicken feathers by sulfuric acid. The physicochemical properties of BA and modified BA (MBA), their effects on Chinese cabbage (CC) yield and nutritional quality, and passivation effects on soil cadmium (Cd) were compared, and the related mechanisms were investigated. SEM-EDS, XRD, and FTIR demonstrated that BA was a CaCO3-type soil amendment, while MBA was a CaSO4-type soil amendment with the loading of amino acid. Compared with BA, MBA significantly increased the fresh weight, soluble sugar, vitamin C (Vc), and protein contents of CC in both non-Cd contaminated soil and Cd contaminated soil, and obviously decreased the nitrate content and Cd uptake of CC in Cd-contaminated soil. After the application of MBA, cadmium species in potted soil were transformed from higher plant availability, representing by exchangeable and carbonate-bound, into lower plant availability, representing by iron-manganese oxide bound, which was identified as the key reason for the significant reduction of Cd content in CC under MBA application.

Effects of grazing intensity on diversity and composition of rhizosphere and non-rhizosphere microbial communities in a desert grassland.

Overgrazing-induced grassland degradation has become a serious ecological problem worldwide. The diversity and composition of soil microbial communities are sensitive to grazing disturbances. However, our understanding is limited with respect to the effects of grazing intensity on bacterial and fungal communities, especially in plant rhizosphere. Using a long-term grazing experiment, we evaluated the diversity and composition of microbial communities in both rhizosphere and non-rhizosphere soils under three grazing intensities (light, moderate, and heavy grazing) in a desert grassland and examined the relative roles of grazing-induced changes in some abiotic and biotic factors in affecting the diversity and composition of microbial communities. Our results showed that soil bacteria differed greatly in diversity and composition between rhizosphere and non-rhizosphere zones, and so did soil fungi. Moderate and heavy grazing significantly reduced the rhizosphere bacterial diversity. Grazing intensity substantially altered the bacterial composition and the fungal composition in both zones but with different mechanisms. While root nitrogen and soil nitrogen played an important role in shaping the rhizosphere bacterial composition, soil-available phosphorus greatly affected the non-rhizosphere bacterial composition and the fungal composition in both soils. This study provides direct experimental evidence that the diversity and composition of microbial communities were severely altered by heavy grazing on a desert grassland. Thus, to restore the grazing-induced, degraded grasslands, we should pay more attention to the conservation of soil microbes in addition to vegetation recovery.

Mechanism for the restoration of degraded typical steppe by nitrogen and phosphorus co-addition.

The reduction of soil nutrient content is one of the major reasons caused grassland degradation in China. Nutrient addition is thus considered as an effective measure for the restoration of degraded grasslands. However, over-fertilization can lead to decrease in plant diversity. To clarify the appropriate amount of nutrient addition and the underlying mechanism that promotes grassland restoration, we set up a nitrogen and phosphorus co-addition experiment in a degraded typical steppe of Inner Mongolia, and examined the responses at community, functional group and species levels to nutrient addition. The results showed that nutrient addition enhanced biomass while did not reduce species richness at the community level. The biomass showed a saturation response with the increases of nutrient addition, which approached saturation under the 12.0 g N·m-2, 3.8 g P·m-2 treatment. Species richness increased significantly under the lower nutrient treatments (N <9.6 g·m-2, P < 3.0 g·m-2) compared with the control, while the two high nutrient treatments did not alter species richness. At the functional group level, biomass and abundance of perennial rhizome grasses increased significantly with the increases of nutrient addition levels. Biomass and density of annuals increased significantly under high nutrient addition levels. However, the abundance and biomass of perennial bunchgrasses and perennial forbs were rarely affected. At the species level, six target species responded differently to nutrient addition. Biomass of Leymus chinensis was significantly increased due to the increase of population density and individual biomass. Biomass of Stipa grandis, Agropyron cristatum and Cleistogenes squarrosa change little. Biomass of Potentilla acaulis and Carex korshinskyi were reduced due to the decreases in individual biomass and population density, respectively. As a measure of restoring degraded grassland, nutrient addition could significantly increase biomass and species diversity, decrease biomass of the degradation indicator species, and increase biomass of perennial rhizomes grasses.

Updated insight into the role of Th2-associated immunity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease with multiple organs involvement, abundant autoantibodies, complement activation, and immune complexes depositions. By regulating inflammation and immune homeostasis, cytokines have been well documented to participate in the pathogenesis of SLE. A number of studies have shown that T helper 2 (Th2)-associated immunity plays an important role in autoimmune diseases, including SLE. Key molecules underlying Th2-related immunity are expected to serve as promising targets for the diagnosis and targeted treatment of SLE. Current progress in SLE pathogenesis and biological treatment strategies has been reviewed, focusing on the latest development in Th2-associated immunity.

Positive legacies of severe droughts in the Inner Mongolia grassland.

Global change-induced extreme droughts are increasing in grasslands worldwide, and drought legacies may greatly affect the responses of grassland ecosystems to these changes. However, it remains poorly understood whether and how severe droughts have a positive legacy effect on grassland productivity. By combining a 4-year precipitation manipulation experiment with a 40-year observational study in a semiarid grassland, we showed that extreme droughts could create strong positive legacies on community productivity and that such legacies could last for multiple years. The mechanism behind this was the coupled effect of the drought-induced increase in annuals and the favorable precipitation pattern that facilitated the flourishing of annuals in subsequent years. This study provides experimental and observational evidence for positive drought legacies and reveals their underlying mechanisms. Our findings suggest that positive drought legacies should be incorporated into Earth system models to better predict the impact of extreme droughts on grassland ecosystems.

An outbreak of pulmonary tuberculosis and a follow-up investigation of latent tuberculosis in a high school in an eastern city in China, 2016-2019.

BACKGROUND: In October 2016, a senior high school student was diagnosed with sputum-smear positive [SS(+)] pulmonary tuberculosis (TB). We conducted an investigation of an outbreak in the school, including among students and teachers diagnosed with latent TB, who we followed until July 2019. METHODS: We defined latent TB infection (LTBI) as a tuberculin skin test (TST) induration of 15mm or larger; probable TB as a chest radiograph indicative of TB plus productive cough/hemoptysis for at least 2 weeks, or TST induration of 15mm or larger; and confirmed TB as two or more positive sputum smears or one positive sputum smear plus a chest radiograph indicative of TB or culture positive with M. tuberculosis. We conducted mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing based on 24 loci in the isolates. RESULTS: Between October 2016 and July 2019, we identified 52 cases, including nine probable, six confirmed, and 37 LTBI cases. The index case-student had attended school continuously despite having TB symptoms for almost three months before being diagnosed with TB. We obtained three isolates from classmates of the index case in 2016; all had identical MIRU-VNTR alleles with the index case. The LTBI rate was lower among students (7.41%, 30/405) than among teachers (26.92%, 7/26) (rate ratio [RR] = 0.28, 95% confidential interval [CI]: 0.13-0.57). Among the 17 students who had latent TB and refused prophylaxis in October 2016, 23.53% (4/17) became probable/confirmed cases by July 2019. None of the six teachers who also refused prophylaxis became probable or confirmed cases. Of the 176 students who were TST(-) in October 2016, 1.70% (3/176) became probable/confirmed cases, and among the 20 teachers who were TST(-), 1 became a probable case. CONCLUSIONS: Delayed diagnosis of TB in the index patient may have contributed to the start of this outbreak; lack of post-exposure chemoprophylaxis facilitated spread of the outbreak. Post-exposure prophylaxis is strongly recommended for all TST-positive students; TST-negative students exposed to an SS(+) case should be followed up regularly so that prophylaxis can be started if LTBI is detected.

Deposition- and transport-dominated erosion regime effects on the loss of dissolved and sediment-bound organic carbon: Evaluation in a cultivated soil with laboratory rainfall simulations.

Erosion-induced soil carbon loss has been identified as a critical process in the global carbon (C) cycle. Surface coverage substantially alters the soil erosion process and the effects of net loss or deposition on soil organic C (SOC). However, information on SOC loss induced by soil erosion at the process level is limited. The aim of this study was to investigate how runoff and erosion regimes affect dissolved and sediment-bound organic C (DOC and SBOC) loss. Thus, six simulated rainfall events were conducted on two laboratory plots (9.75 m × 1.83 m) with different surface coverages (17-83%) and coverage distributions (upslope vs. downslope) using polypropylene geotextiles. The results showed that the variability in the process of runoff and sediment yield existed as a result of altered surface coverage over the erosion zone (SSerosion zone) and covered zone (SScovered zone) on the slope. Thus, the erosion regimes can be identified as deposition- and transport-dominated processes, which were the main soil erosion subprocesses. The surface coverage located downslope (SCtop-bottom slope) can more efficiently reduce runoff (21.9-85.7%) and sediment (67.6-98.3%) than the SCbottom-top slope (runoff: 20.1-83.0%; sediment: 35.0-93.3%), which has the surface coverage located upslope. DOC (8.0-11.3 mg L-1) and SBOC (0.3-0.5 mg g-1) in the deposition-dominated process on the SCtop-bottom slope were higher than in the transport-dominated process on the SCbottom-top slope (DOC: 6.8-10.2 mg L-1; SBOC: 0.2-0.3 mg g-1). The loading of DOC and SBOC was largely dependent on runoff and sediment yield, and DOC load contributed 83.9-89.7% of the SOC loss. Overall, laboratory results highlighted the soil C loss at different hydrological and erosion regimes (deposition- vs. transport-dominated process). This study provides important information that can be used to facilitate further implementations such as watershed modeling of soil C dynamics and the corresponding decision-making processes.

Effects of Simulated Gravel on Hydraulic Characteristics of Overland Flow Under Varying Flow Discharges, Slope Gradients and Gravel Coverage Degrees.

To quantify the hydraulic characteristics of overland flow on gravel-covered slopes, eight flow discharges (Q) (8.44-122 L/min), five slope gradients (J) (2°-10°) and four gravel coverage degrees (Cr) (0-30%) were examined via a laboratory flume. The results showed that (1) gravel changed flow regime. Gravel increased the Reynolds number (Re) by 2.94-33.03%. Re were less affected by J and positively correlated with Cr and Q. Gravel decreased the Froude number (Fr) by 6.83-77.31%. Fr was positively correlated with Q and J and negatively correlated with Cr. (2) Gravel delayed the flow velocity (u) and increased the flow depth (h) and flow resistance (f). Gravel reduced u by 1.20-58.95%. u was positively correlated with Q and J and negatively correlated with Cr. Gravel increased h by 0.12-2.41 times. h was positively correlated with Q and Cr and negatively correlated with J. Gravel increased f by 0.15-18.42 times. f were less affected by J, positively correlated with Cr and negatively correlated with Q. (3) The relationships between hydraulic parameters and Q, J and Cr identified good power functions. Hydraulic parameters were mainly affected by Cr. These results can guide the ecological construction of soil and water conservation.

Enlarged responsivity-ZnO honeycomb nanomaterials UV photodetectors with light trapping effect.

The ability of ZnO photodetectors to absorb UV light plays a key role in enhancing responsivity and performance in electronic, optical, and photonic devices. Herein, the light trapping effect of ZnO is used to design and fabricate a novel honeycomb-like ZnO nanomaterial-based UV photodetector with an excellent photoelectric performance. Compared with the traditional ZnO film UV photodetector, the photoresponsivity of the film with honeycomb nanomaterials can reach up to 4.79 A W-1, which is an improvement of about 300 times. In addition, the honeycomb ZnO nanomaterials UV photodetectors exhibit an improved light absorption, a very photo-to-dark current ratio (2.46 × 103), and an excellent detectivity (4.61 × 1012 Jones). The ZnO honeycomb nanostructure synthesized in this work exhibits a strong trapping effect, providing new insights into the research of nanomaterials used for UV photodetectors.

Long-term Low-Dose Sucrose May Prevent Migraine: Two Double-Blinded Randomized Controlled Pilot Trials.

AIMS: To evaluate the efficacy of sucrose in the prevention of migraine attacks. METHODS: Two randomized double-blinded pilot trials were conducted, one in college students and one in adults. Migraineurs were randomized into two groups that each received an oral liquid: for students, sucrose 5 g/day (s-group; n = 12) or glucose 2.5 g/day (g-group; n = 10) for 3 months; and for adults, sucrose 5 g/day (s-group; n = 10) or fructose 2.5 g/day (f-group; n = 9) for 6 months. The primary endpoint was the frequency of migraine attacks per month, and the secondary endpoints were mean duration and severity of migraine per attack. Continuous measurements were described as mean ± standard deviation (SD). The overall significance of the effects between different groups was tested using repeated measures analysis of variance (RANOVA), and the efficacy was evaluated using an intent-to-treat analysis. RESULTS: Migraine frequency in the students declined significantly in the g-group (mean reduction ± SD: 0.65 ± 0.71; P < .01), but not in the s-group (0.33 ± 2.02; P = .58). RANOVA results suggested that the secondary endpoints significantly declined over time (all P < .01) with no differences between the groups. In the adult trial, mixed-effects model analysis showed that both the primary and secondary endpoints significantly declined over time with no significant differences between the groups. CONCLUSION: Long-term consumption of a 5-g dose of sucrose for adult migraineurs or a 2.5-g dose of glucose for college student migraineurs may be as effective as preventive treatments.

Are Glucose and Insulin Metabolism and Diabetes Associated with Migraine? A Community-Based, Case-Control Study.

AIMS: To investigate the association between glucose and insulin metabolism and migraine, as well as between diabetes mellitus (DM) and migraine, at a Chinese community level. METHODS: A community-based, case-control study was performed in Heihe City, China. A survey was conducted door to door by eight trained investigators. Migraine was diagnosed using the International Classification of Headache Disorders (ICHD-III) beta criteria. A total of 2,023 participants completed a questionnaire, underwent a physical examination, and donated fasting blood. After excluding 191 with reported DM, 1,832 participants were included in the study. Of these, 86 participants with migraine and 95 without migraine participated in a 75-g oral glucose tolerance test. Glycosylated hemoglobin (HbA1c) was assessed at 0 minutes and serum glucose and insulin levels were measured at 0, 30, 60, and 120 minutes after glucose loading. Data with skewed distributions were compared using rank sum test, and the associations between DM and migraine were analyzed with logistic regression. RESULTS: There were no significant differences in HbA1c, homeostatic model assessment-insulin resistance (HOMA-IR), ß-cell function index of HOMA, or quantitative insulin sensitivity check index (QUICKI) between the participants with migraine and without migraine. When participants without migraine were classified into DM, prediabetes, and normal glucose subgroups and compared with the corresponding migraine subgroups, participants in the migraine subgroup with prediabetes presented higher levels of fasting insulin and HOMA-IR and a lower QUICKI than the nonmigraine subgroup with prediabetes. Moreover, DM was negatively associated with migraine in the 181 subjects who participated in the OGTT; however, no association was found when all 1,832 participants were considered. CONCLUSION: Insulin resistance seems to exist in individuals with both migraine and prediabetes, and there is a possible negative association between DM and migraine.

Identification of interacting proteins of the TaFVE protein involved in spike development in bread wheat.

WD-40 repeat-containing protein MSI4 (FVE)/MSI4 plays important roles in determining flowering time in Arabidopsis. However, its function is unexplored in wheat. In the present study, coimmunoprecipitation and nanoscale liquid chromatography coupled to MS/MS were used to identify FVE in wheat (TaFVE)-interacting or associated proteins. Altogether 89 differentially expressed proteins showed the same downregulated expression trends as TaFVE in wheat line 5660M. Among them, 62 proteins were further predicted to be involved in the interaction network of TaFVE and 11 proteins have been shown to be potential TaFVE interactors based on curated databases and experimentally determined in other species by the STRING. Both yeast two-hybrid assay and bimolecular fluorescence complementation assay showed that histone deacetylase 6 and histone deacetylase 15 directly interacted with TaFVE. Multiple chromatin-remodelling proteins and polycomb group proteins were also identified and predicted to interact with TaFVE. These results showed that TaFVE directly interacted with multiple proteins to form multiple complexes to regulate spike developmental process, e.g. histone deacetylate, chromatin-remodelling and polycomb repressive complex 2 complexes. In addition, multiple flower development regulation factors (e.g. flowering locus K homology domain, flowering time control protein FPA, FY, flowering time control protein FCA, APETALA 1) involved in floral transition were also identified in the present study. Taken together, these results further elucidate the regulatory functions of TaFVE and help reveal the genetic mechanisms underlying wheat spike differentiation.

Methylation of a panel of genes in peripheral blood leukocytes is associated with colorectal cancer.

The relationship between the DNA methylation status of the CpG islands of multiple genes in blood leukocytes in CRC susceptibility and prognosis, as well as possible interactions with dietary factors on CRC risk are unclear. We carried out a case-control study including 421 CRC patients and 506 controls to examine the associations between six genes (AOX-1, RARB2, RERG, ADAMTS9, IRF4, and FOXE-1), multiple CpG site methylation (MCSM) and susceptibility to CRC. High-level MCSM (MCSM-H) was defined as methylation of greater than or equal to 2 of 5 candidate genes (except for RARB2); low-level MCSM (MCSM-L) was when 1 candidate gene was methylated; non-MCSM was when none of the candidate genes were methylated. Blood cell-derived DNA methylation status was detected using methylation-sensitive high-resolution melting analysis. The hypermethylation status of each individual gene was statistically significantly associated with CRC. MCSM status was also associated with CRC (OR = 1.54, 95% CI: 1.15-2.05, P = 0.004). We observed interactions between a high level of dietary intake of cereals, pungent food, and stewed fish with brown sauce, age (older than 60 yrs), smoking and hypermethylation on risk of CRC. MCSM in peripheral blood DNA may be an important biomarker for susceptibility to CRC.

Prevalence, Associated Factors, and Impact on Quality of Life of Migraine in a Community in Northeast China.

AIMS: To validate the Chinese version of the Identification of Migraine screener (ID-Migraine), assess migraine prevalence, identify potential associated factors, and assess the impact of migraine on quality of life in a community in Harbin, PR China. METHODS: A community-based, cross-sectional study was conducted in the Songbei district of Harbin. After excluding the people who did not usually reside in the community, 2,588 adults were invited to participate in the study. Eligible participants underwent a physical examination before completing a questionnaire addressing demographics, medical history, and other features. Additionally, the ID-Migraine was validated by using International Classification of Headache Disorders-3 criteria, with 94 participants screening positive and 100 participants screening negative for migraine as diagnosed through a telephone interview. The diagnostic accuracy of ID-Migraine was evaluated by sensitivity and specificity, and a multivariate logistic regression model was used to determine the association between migraine and associated factors. RESULTS: A total of 1,143 subjects completed the questionnaire (response rate 44.2%). The prevalence of migraine was 8.9%, with a male to female prevalence ratio of 1:3.30 (3.7% versus 12.2%; P < .001). The sensitivity (90.6%; 95% confidence interval [CI] = 75.0% to 97.9%) and specificity (71.4%; 95% CI = 60.0% to 81.2%) of the ID-Migraine were satisfactory. Multivariate logistic regression analyses suggested female sex, depression, coronary heart disease (CHD), chronic obstructive pulmonary disease (COPD), ischemic stroke (IS), and hypertension were positively associated with migraine, whereas age and education level were negatively associated with migraine. Migraine was shown to significantly impact quality of life. CONCLUSION: Migraine is a highly prevalent disease that can significantly affect quality of life. Age, sex, education level, depression, CHD, COPD, IS, and hypertension were all associated with migraine.

The Prevalence and Awareness of Migraine Among University Students in Harbin, China.

AIMS: To determine the prevalence and the awareness of migraine among university students in Harbin, China. METHODS: A cross-sectional study of students was conducted in Harbin Medical University from April 1 to June 30, 2012. The Chinese version of the Identification of Migraine Screener (ID-Migraine) was used as the screening tool, and the awareness of migraine was evaluated by a structured questionnaire. A subgroup of the students was randomly selected to fill out the questionnaire again to evaluate its test-retest reliability. The internal consistency reliability and structured validity were tested using Cronbach's alpha coefficient and exploratory factor analyses. RESULTS: Of the 5,129 registered students, 4,406 students (85.9%) signed a consent form and completed the questionnaire. Three hundred ninety-five students were screened positive for migraine, with a prevalence of 9.0%, and the migraine prevalence increased with age (z=-2.82, P<.01). Gender (χ²=0.12, P=.73) and body mass index (χ²=0.51, P=.78) did not significantly influence migraine prevalence, and the prevalence showed no significant difference between medical and nonmedical students (χ²=2.10, P=.15). The awareness of fundamental details (definition, classification, symptoms), treatment, and trigger factors of migraine were 40.4%, 42.4%, and 68.6%, respectively. The test-retest reliability of these parts of the questionnaire was 0.61 (95% confidence interval [CI]: 0.48-0.75), 0.77 (95% CI: 0.66-0.88), and 0.80 (95% CI: 0.69-0.91), respectively. Three components accumulatively explained 52.1% of the total variance of the scale, and the rotated factor loadings (the correlation coefficient between the items and the common factor) in each part were all higher than 0.50 excluding item C11. CONCLUSION: The prevalence of migraine in university students was 9.0%, which is comparable to the prevalence found in Chinese adults from the general population in two previous studies. University students have limited awareness of migraine.

[Effect of alpha-terthienyl on protein, esterase and lipid peroxidation of Aedes albopictus larvae].

OBJECTIVE: To study the effect of alpha-terthienyl (alpha-T) on protein, esterase and lipid peroxidation of Aedes albopictus larvae. METHODS: Sensitive and resistant strains of Aedes albopictus stage IV larvae were used. Bradford method was used to detect protein content. The breeding fluid of experiment group contained alpha-T (5.34 microg/L), and control group contained only acetone (3.95 microg/L). Histochemistry method was used to detect esterase activity. Larvae in the experiment group were cultured in fluid containing alpha-T (6.24 microg/L) but no alpha-T in the control group. TBA method was used to detect malondialdehyde (MDA). Larvae of the sensitive strain were divided into 5 sub-groups: A - acetone control (containing acetone 3.95 microg/L), B - ultra-violet irradiation (UV) control (same with A but treated by UV), C, D, E - experiment groups with alpha-T (4.58, 5.34 and 6.24 microg/L respectively). All groups were kept in dark condition for 1 hour, followed by UV for 1 hour (except group A), then fed under normal condition. RESULTS: With UV and alpha-T, the protein content of experiment group (1.225 mg/ml) was higher than that of control (1.120 mg/ml) (P<0.05) in sensitive strain; that of experiment group (1.199 mg/ml) was higher than that of control (1.114 mg/ml) (P<0.05) in the resistant strain. After 2, 4, 6, and 8 hour treated by both alpha-T and UV, the esterase activity all decreased in experiment group, and reached to the lowest 8 hours later (P<0.05). MDA contents was 2.286 nmol/mg protein in acetone control group and 2.322 nmol/mg protein in UV control, but 3.156, 4.188 and 4.684 nmol/mg protein respectively in the 3 experiment groups after treated by alpha-T and UV. The higher dose of alpha-T, the higher content of MDA (P<0.05). CONCLUSION: Under UV, alpha-T can increase the protein and MDA content of the larvae of Ae. albopictus but decrease the esterase activity.