T lymphocytes are the major components of adaptive immunity in Behçet's syndrome (BS) pathology. However, the precise mechanism of T‐cell‐induced inflammatory condition remains to be determined. We ...applied bulk sequencing of the T‐cell receptor (TCR) β chain in peripheral blood samples from 45 patients with BS and 10 healthy donors as controls. TCR repertoires in BS patients displayed more clonality and less diversity than in healthy donors. Male patients exhibited lower diversity metrics of TCR and had a larger proportion in the top 10 clones than females (p = 0.016). There were no TCR clonality differences in other clinical features, such as age, disease duration, organ involvement, disease severity, and activity. By “Grouping of Lymphocyte Interactions by Paratope Hotspots” (GLIPH2) for antigen prediction, we found distinct 2477 clusters of TCR‐β sequences that potentially recognize similar antigens shared between BS patients. We observed clonal T‐cell expansion in BS patients. Sexual differences in TCR clonal expansion and public TCR groups deserve further study to reveal the underline T‐cell‐mediated immunity in BS.
Bulk sequencing of the TCR repertoires in BS patients displayed more clonality and less diversity than in healthy donors. Male patients exhibited lower diversity metrics of TCR than females. GLIPH2 predicted distinct clusters of TCR‐β sequences in BS patients.
Lipid metabolism imbalance has been recognized as one of the major drivers of impaired glucose metabolism in the context of type 2 diabetes mellitus (T2DM), the rates of which are steadily increasing ...worldwide. Impaired glucose regulation (IGR) plays a vital role in the prevention and treatment of T2DM. The goal of this study was to further clarify whether the combination of plant sterols (PS) and omega-3 fatty acids yields any synergistic effect that enhances the prevention and treatment of IGR.
A total of 200 participants were randomized to receive PS and omega-3 fatty acids (n = 50), PS alone (n = 50), omega-3 fatty acids alone (n = 50), or placebo soy bean powder plus placebo capsules (n = 50) for 12 weeks. Patient characteristics including body composition, blood pressure, glucose metabolism (Fasting plasma glucose (FPG), fasting insulin (FINS), glycosylated hemoglobin (HbA1c), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)), lipid metabolism (TG, TC, HDL-C, LDL-C) and inflammatory factors (Hs-CRP, IL-6) were all monitored in these IGR individuals.
Compared to the placebo group, the group receiving the combined intervention exhibited significantly decreased TG, HDL-C, FBG, HOMA-IR and HbA1c. Omega-3 fatty acids alone were associated with significant reductions in waistline, TG, FBG, HOMA-IR and Hs-CRP. PS alone was only associated with decreased TG and Hs-CRP. No interventions produced significant changes in body weight, BMI, blood pressure, FINS, body fat percentage, visceral fat rating, TC, LDL-C or IL-6.
In summary, this study has demonstrated for the first time that PS, omega-3 fatty acids or the combination thereof significantly improved inflammation, insulin resistance, as well as glucose and lipid metabolism in IGR individuals. These findings may provide a scientific basis for the development of nutritional products incorporating PS and omega-3 fatty acids, and also for the development of nutritional supplement strategies aimed at preventing the development of disease in the IGR population.
Photodynamic therapy (PDT) is a promising treatment modality for tumor suppression. However, the hypoxic state of most solid tumors might largely hinder the efficacy of PDT. Here, a functional ...covalent organic framework (COF) is fabricated to enhance PDT efficacy by remodeling the tumor extracellular matrix (ECM). Anti-fibrotic drug pirfenidone (PFD) is loaded in an imine-based COF (COFTTA-DHTA) and followed by the decoration of poly(lactic-co-glycolic-acid)-poly(ethylene glycol) (PLGA-PEG) to fabricate PFD@COFTTA-DHTA@PLGA-PEG, or PCPP. After injected intravenously, PCPP can accumulate and release PFD in tumor sites, leading to down-regulation of ECM compenents such as hyaluronic acid (HA) and collagen I. Such depletion of tumor ECM reduces the intratumoral solid stress, a compressive force exerted by the ECM and cells, decompresses tumor blood vessels, and increases the density of effective vascular areas, resulting in significantly improved oxygen supply in tumor. Furthermore, PCPP-mediated tumor ECM depletion also enhances the tumor uptake of subsequently injected Protoporphyrinl IX (PPIX)-conjugated peptide formed nanomicelles (NM-PPIX) due to the improved enhanced permeability and retention (EPR) effect. Both the alleviated tumor hypoxia and improved tumor homing of photosensitizer (PS) molecules after PCPP treatment significantly increase the reactive oxygen species (ROS) generation in tumor and therefore realize greatly enhanced PDT effect of tumor in vivo.
A covalent organic framework (COF)-based nanosystem PCPP was fabricated to enhance tumor photodynamic therapy (PDT). PCPP can trigger the depletion of tumor extracellular matrix (ECM), leading to improved oxygen supply as well as photosensitizer uptake in tumor to achieve enhanced tumor PDT. Display omitted
Agonists of stimulators of interferon genes (STING) are a promising class of immunotherapeutics that trigger potent innate immunity. However, the therapeutic efficacy of conventional STING agonists, ...such as 2′,3′-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), is severely restricted to poor cytosolic delivery and lacks the capacity to promote the recognition of tumor-specific antigens. Here, we tackle these challenges through a nanovaccine platform based on Fenton-reactive and STING-activating nanoparticles, synergistically contributing to the generation of tumor-cell-derived apoptotic bodies (ABs). ABs loaded with exogenous cGAMP are readily phagocytosed by antigen-presenting cells (APCs), as a Trojan horse for rendering tumor cells with high immunogenicity instead of a noninflammatory response. This leads to enhanced STING activation and an improved tumor-specific antigen presentation ability, boosting the adaptive immunity in collaboration with innate immune. The strategy of exploiting a metal-based nanovaccine platform possesses great potential to be clinically translated into a trinitarian system of diagnosis, treatment, and prognosis.
Coronavirus disease 2019 (COVID-19), caused by the novel human coronavirus SARS-CoV-2, is currently a major threat to public health worldwide. The viral spike protein binds the host receptor ...angiotensin-converting enzyme 2 (ACE2) via the receptor-binding domain (RBD), and thus is believed to be a major target to block viral entry. Both SARS-CoV-2 and SARS-CoV share this mechanism. Here we functionally analyzed the key amino acid residues located within receptor binding motif of RBD that may interact with human ACE2 and available neutralizing antibodies. The in vivo experiments showed that immunization with either the SARS-CoV RBD or SARS-CoV-2 RBD was able to induce strong clade-specific neutralizing antibodies in mice; however, the cross-neutralizing activity was much weaker, indicating that there are distinct antigenic features in the RBDs of the two viruses. This finding was confirmed with the available neutralizing monoclonal antibodies against SARS-CoV or SARS-CoV-2. It is worth noting that a newly developed SARS-CoV-2 human antibody, HA001, was able to neutralize SARS-CoV-2, but failed to recognize SARS-CoV. Moreover, the potential epitope residues of HA001 were identified as A475 and F486 in the SARS-CoV-2 RBD, representing new binding sites for neutralizing antibodies. Overall, our study has revealed the presence of different key epitopes between SARS-CoV and SARS-CoV-2, which indicates the necessity to develop new prophylactic vaccine and antibody drugs for specific control of the COVID-19 pandemic although the available agents obtained from the SARS-CoV study are unneglectable.
Functionalized P,C-stereogenic tertiary phosphine oxides were prepared by the addition of (R P)-menthyl phenylphosphine oxide to activated olefins, in high drP and drC, and were isolated in excellent ...yields. The reaction was readily catalyzed by Ca(OH)2 or occurred with gentle heating. A wide range of substrates, including vinyl ketones, esters, nitriles, and nitro alkenes, can be used in the reaction.
Since the collapse of the Soviet Union, the crop cultivation structure in the Aral Sea Basin has changed dramatically, and these changes are worth studying. However, historical crop remote sensing ...mapping at the watershed scale remains challenging, especially crop misclassification at the cropland edge due to mixed pixels. Therefore, we proposed a field segmentation approach to constrain field edges based on time‐series Sentinel‐2 remote sensing images and the Google Earth Engine platform and then employed the random forest algorithm to perform crop classification based on time series Landsat/Sentinel‐2 images and crop phenology information to produce historical crop maps in the Aral Sea Basin from the 1990s onward. The results showed that the intersection over union between the extracted field edges and in situ‐measured field size data was 0.65. The overall accuracy of crop mapping was 95.2% in 2019. Then, we extended our method to historical mapping over the 1991–2015 period with accuracies ranging from 82.8% to 91.3%. Moreover, our method applied to historical mapping works well in terms of accuracy and policy matching. These findings indicate that our method can accurately distinguish cropland edges to reduce classification errors due to mixed pixels. This method is promising for solving the cropland edge problem for historical crop mapping in the Aral Sea Basin and can potentially provide a reference for historical crop classification in other watersheds of the world.
Programmed cell death (PCD)—apoptosis, autophagy and programmed necrosis—is any pathological form of cell death mediated by intracellular processes. Ototoxic drugs, ageing and noise exposure are some ...common pathogenic factors of sensorineural hearing loss (SNHL) that can induce the programmed death of auditory hair cells through different pathways, and eventually lead to the loss of hair cells. Furthermore, several mutations in apoptotic genes including DFNA5, DFNA51 and DFNB74 have been suggested to be responsible for the new functional classes of monogenic hearing loss (HL). Therefore, in this review, we elucidate the role of these three forms of PCD in different types of HL and discuss their guiding significance for HL treatment. We believe that further studies of PCD pathways are necessary to understand the pathogenesis of HL and guide scientists and clinicians to identify new drug targets for HL treatment.
The authors review accumulating evidence pointing out that programmed cell death pathways, including apoptosis, autophagy and necrosis, play key roles in ultimate fates of auditory hair cells, when cells suffer adverse factors. These three forms of PCD may jointly decide occurrence of hearing loss.
•Continuous applications of organic materials increased the C and N fraction content.•Rice straw greatly increased the soil organic C and dissolved organic C content.•Pig manure greatly increased ...soil microbial biomass N and dissolved total N content.
Soil organic carbon (C) and nitrogen (N) pools are the most important soil components, and their characteristics directly or indirectly determine the stability of the soil structure and the soil fertility. Using a rice fields experiment in the coastal areas of Southeast China, how a long-term (10 years) continuous application of organic materials consisting of green manure (Chinese milk vetch), pig manure, and rice straw affected the soil C and N fractions were studied. The results showed that 10-year continuous applications of organic materials to the paddy fields significantly increased the C fraction content in terms of parameters such as the soil organic C (SOC), microbial biomass C (MBC), and active organic C (AOC). It also increased the soil N fraction content, including the soil total N (TN), dissolved total N (DTN), microbial biomass N (MBN), and active N. The rice straw return had the most significant effect in relation to increasing the SOC and dissolved organic C (DOC), with 23.9% and 42.3% increases, respectively, compared to applying chemical fertilizer alone. Organic pig manure had the most significant effect on the soil MBN and DTN, with 49.3% and 50.7% increases, respectively, compared to the application of chemical fertilizer alone. MBC and MBN are the primary components of soil AOC and active N, respectively. The application of organic materials increased the ratio of soil MBC and AOC to SOC, as well as the ratio of MBN, DTN, and active N to the soil TN. Our findings indicated that long-term applications of organic materials could improve and enhance paddy soil fertility and promote increased rice yields.
AIM To investigate whether patients with refractory epilepsy and healthy infants differ in gut microbiota(GM),and how ketogenic diet(KD) alters GM.METHODS A total of 14 epileptic and 30 healthy ...infants were recruited and seizure frequencies were recorded. Stool samples were collected for 16 S r DNA sequencing using the Illumina Miseq platform. The composition of GM in each sample was analyzed with MOTHUR,and intergroup comparison was conducted by R software.RESULTS After being on KD treatment for a week,64% of epileptic infants showed an obvious improvement,with a 50% decrease in seizure frequency. GM structure in epileptic infants(P1 group) differed dramatically from that in healthy infants(Health group). Proteobacteria,which had accumulated significantly in the P1 group,decreased dramatically after KD treatment(P2 group). Cronobacter predominated in the P1 group and remained at a low level both in the Health and P2 groups. Bacteroides increased significantly in the P2 group,in which Prevotella and Bifidobacterium also grew in numbers and kept increasing.CONCLUSION GM pattern in healthy infants differed dramatically from that of the epileptic group. KD could significantly modify symptoms of epilepsy and reshape the GM of epileptic infants.
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