Abstract
The National Genomics Data Center (NGDC), which is a part of the China National Center for Bioinformation (CNCB), provides a family of database resources to support the global academic and ...industrial communities. With the rapid accumulation of multi-omics data at an unprecedented pace, CNCB-NGDC continuously expands and updates core database resources through big data archiving, integrative analysis and value-added curation. Importantly, NGDC collaborates closely with major international databases and initiatives to ensure seamless data exchange and interoperability. Over the past year, significant efforts have been dedicated to integrating diverse omics data, synthesizing expanding knowledge, developing new resources, and upgrading major existing resources. Particularly, several database resources are newly developed for the biodiversity of protists (P10K), bacteria (NTM-DB, MPA) as well as plant (PPGR, SoyOmics, PlantPan) and disease/trait association (CROST, HervD Atlas, HALL, MACdb, BioKA, BioKA, RePoS, PGG.SV, NAFLDkb). All the resources and services are publicly accessible at https://ngdc.cncb.ac.cn.
Graphical Abstract
Graphical Abstract
Generally, long wavelength absorbed near‐infrared II (NIR‐II) dyes have a low fluorescence efficiency in aggregate states for aggregate‐caused quenching effect, simultaneously enhancing efficiency ...and extending absorption is a challenging issue for NIR‐II dyes. Here, three benzo1,2‐c:4,5‐c'bis1,2,5thiadiazole (BBT) derivatives (TPA‐BBT, FT‐BBT, and BTBT‐BBT) are used to clarify fluorescence quenching mechanisms. When the BBT derivatives are doped into a small molecule matrix, they show quite different fluorescence behaviors. Structure‐distorted TPA‐BBT displays fluorescence quenching originating from short‐range exchange interaction, while FT‐BBT and BTBT‐BBT with a co‐planar‐conjugated backbone exhibit concentration‐dependent quenching processes, namely changing from long‐range dipole‐dipole interaction to exchange interaction, which could be majorly ascribed to large spectral overlap between absorption and emission. By precisely tuning doping concentration, both FT‐BBT and BTBT‐BBT nanoparticles (NPs) present the optimal NIR‐II fluorescence brightness at ∼2.5 wt% doping concentration. The doped NPs have good biocompatibility and could be served as fluorescence contrast agents for vascular imaging with a high resolution under 980‐nm laser excitation. Those paradigms evidence that molecular doping can promote fluorescence efficiency of long wavelength‐absorbed NIR‐II fluorophores via suppressing long‐range energy migration.
Long‐wavelength‐absorbed NIR‐II fluorophores with co‐planar conformation are synthesized to investigate the fluorescence quenching effect in an aggregate state. The experimental results reveal that the quenching originates from Föster‐like long‐range dipole‐dipole interaction for large spectral overlap degree promoting energy migration and dissipation via nonradiative pathways. So, low content doping can block the long‐range interaction and enhance NIR‐II fluorescence efficiency.
A 56-day growth trial was conducted to investigate the effects of dietary yeast hydrolysate on the growth performance, antioxidation, immune response and resistance against Aeromonas hydrophila in ...largemouth bass. Four experimental diets were prepared with yeast hydrolysate levels of 0% (Y0), 1.5% (Y1.5), 3.0% (Y3.0) and 4.5% (Y4.5). Each diet was randomly assigned to triplicate 150-L tanks and each tank was stocked with 30 largemouth bass (initial body weight, IBW = 7.71 ± 0.02 g). A challenge test was carried out after the feeding trial by injecting A. hydrophila intraperitoneally for 4-day observation. The results showed that the FBW and WGR in Y1.5 group were significantly higher than those in Y0 group (P < 0.05) and the feed conversion ratio (FCR) got the lowest value in Y1.5 group. And the hydrolysate supplement significantly increased the 4-day cumulative survival rate after the bacterial challenge (P < 0.05). The plasma malondialdehyde was lower in the yeast hydrolysate supplement groups in both pre- and post-challenge test (P < 0.05), while the plasma C3 increased (P < 0.05). In post-challenge test, the plasma superoxide dismutase (SOD) and catalase (CAT) activities increased in the Y1.5 and Y3.0 groups respectively (P < 0.05), and plasma lysozyme in Y1.5 group and the plasma IgM in Y3.0 group were higher than those in others respectively (P < 0.05). For the q-PCR results, in post-challenge test, the hepatic hep2 expression level in Y1.5 and Y4.5 groups were both significantly higher than those in others (P < 0.05), as well as il-8 in Y3.0 group. The spleen hif-1alpha and tgf-beta1 expression levels in Y4.5 group were all significantly lower than those in others (P < 0.05), while the gilt was significantly higher (P < 0.05) in the post-challenge test. And the expression levels of spleen tnf-alpah1 in Y1.5 and Y3.0 groups and il-8 in Y3.0 group were all significantly higher than those in other groups (P < 0.05) in the post-challenge test. The head kidney gilt expression level was significantly higher in the yeast hydrolysate supplement groups compared with the Y0 group (P < 0.05), and the head kidney il-8 expression level in Y1.5 group was significant higher than those in other groups in post-challenge test (P < 0.05). The present results indicated dietary yeast hydrolysate improved the antioxidant ability and enhanced the immune response of largemouth bass without negative effect on growth. And 1.5% or 3.0% of dietary yeast hydrolysate was recommended for largemouth bass based on the present results.
•1.5% or 3.0% dietary yeast hydrolysate improved the antioxidation and immunity of largemouth bass without negative effect.•The dietary yeast hydrolysate enhanced the liver antibacterial activity by stimulating the hep2 expressions.•The dietary yeast hydrolysate improved antioxidation through the gilt and hif-1alpha expressions.•The dietary yeast hydrolysate decreased the inflammation of head kidney by regulating proinflammatory cytokines.
Cyclophosphamide-induced testosterone deficiency (CPTD) during the treatment of cancers and autoimmune disorders severely influences the quality of life of patients. Currently, several guidelines ...recommend patients suffering from CPTD receive testosterone replacement therapy (TRT). However, TRT has many disadvantages underscoring the requirement for alternative, nontoxic treatment strategies. We previously reported bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exos) could alleviate cyclophosphamide (CP)-induced spermatogenesis dysfunction, highlighting their role in the treatment of male reproductive disorders. Therefore, we further investigated whether BMSCs-exos affect autophagy and testosterone synthesis in Leydig cells (LCs). Here, we examined the effects and probed the molecular mechanisms of BMSCs-exos on CPTD in vivo and in vitro by detecting the expression levels of genes and proteins related to autophagy and testosterone synthesis. Furthermore, the testosterone concentration in serum and cell-conditioned medium, and the photophosphorylation protein levels of adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) were measured. Our results suggest that BMSCs-exos could be absorbed by LCs through the blood-testis barrier in mice, promoting autophagy in LCs and improving the CP-induced low serum testosterone levels. BMSCs-exos inhibited cell death in CP-exposed LCs, regulated the AMPK-mTOR signaling pathway to promote autophagy in LCs, and then improved the low testosterone synthesis ability of CP-induced LCs. Moreover, the autophagy inhibitor, 3-methyladenine (3-MA), significantly reversed the therapeutic effects of BMSCs-exos. These findings suggest that BMSCs-exos promote LC autophagy by regulating the AMPK-mTOR signaling pathway, thereby ameliorating CPTD. This study provides novel evidence for the clinical improvement of CPTD using BMSCs-exos.
Insulin-like growth factor 1 (IGF1) is an important growth factor modulating development, homeostasis, and aging. However, whether and how circulating IGF1 concentrations influence early death risk ...in the general population remains largely unknown.
We included 380 997 participants who had serum IGF1 measurement and no history of cancer, cardiovascular disease (CVD), or diabetes at baseline from UK Biobank, a prospective cohort study initiated in 2006-2010. Restricted cubic splines and Cox proportional hazards regression models were used to assess the association between baseline IGF-1 concentrations and all-cause and cause-specific mortality.
Over a median follow-up of 8.8 years, 10 753 of the participants died, including 6110 from cancer and 1949 from CVD. Dose-response analysis showed a U-shaped relationship between IGF1 levels and mortality. Compared to the fifth decile of IGF1, the lowest decile was associated with 39% (95% CI: 29-50%), 20% (95% CI: 8-34%), and 39% (95% CI: 14-68%) higher risk of all-cause, cancer, and CVD mortality, respectively, while the highest decile was associated with 17% (95% CI: 7-28%) and 38% (95% CI: 11-71%) higher risk of all-cause and CVD mortality, respectively. The results remained stable in detailed stratified and sensitivity analyses.
Our findings indicate that both low and high concentrations of serum IGF1 are associated with increased risk of mortality in the general population. Our study provides a basis for future interrogation of underlying mechanisms of IGF1 in early death occurrence and possible implications for mitigating the risk.
Recently, the ZrO2-based catalysts for PDH exhibited high activity owing to the formation of oxygen vacancy and coordinatively unsaturated Zr (Zrcu) sites. However, industrial C3H8 raw gases ...typically contain trace amounts of oxygen at 10–1000 ppm, which can significantly decrease the PDH activity of nano-sized ZrO2 catalyst, because that oxygen vacancy can be filled by the O2 molecules rapidly, while the rate of lattice oxygen consumption is relatively slow. Here, highly dispersed NiOx species loading on ZrO2 significantly increased C3H6 formation rate (up to 6.6 times) and decreased the activation energy. The strong interaction between NiOx species and ZrO2 enhances the ability of ZrO2 to release its lattice oxygen, and increases the concentration of oxygen vacancy and unsaturated Zr-O acid-base pairs for PDH. This strategy can expand to other metal oxides interacted with ZrO2 to eliminate the inhibiting effect of trace oxygen, such as GaOx, CoOx, CrOx, LaOx, and InOx.
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•A trace O2 in C3H8/N2 feed gas can significantly decrease the PDH activity of nano-sized ZrO2 catalyst.•Highly dispersed NiOx species loading on ZrO2 significantly increased C3H6 formation rate under oxygen-lean PDH condition.•The strong interaction between NiOx and ZrO2 enhances the ability of ZrO2 to release lattice oxygen and and form oxygen vacancy.
To compare neoadjuvant chemotherapy (nCT) with CAPOX alone versus neoadjuvant chemoradiotherapy (nCRT) with capecitabine in locally advanced rectal cancer (LARC) with uninvolved mesorectal fascia ...(MRF).
nCRT is associated with higher surgical complications, worse long-term functional outcomes, and questionable survival benefits. Comparatively, nCT alone seems a promising alternative treatment in lower-risk LARC patients with uninvolved MRF.
Patients between June 2014 and October 2020 with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to nCT group with 4 cycles of CAPOX (Oxaliplatin 130 mg/m2 IV day 1 and Capecitabine 1000 mg/m2 twice daily for 14 d. Repeat every 3 wk) or nCRT group with Capecitabine 825 mg/m² twice daily administered orally and concurrently with radiation therapy (50 Gy/25 fractions) for 5 days per week. The primary end point is local-regional recurrence-free survival. Here we reported the results of secondary end points: histopathologic response, surgical events, and toxicity.
Of the 663 initially enrolled patients, 589 received the allocated treatment (nCT, n=300; nCRT, n=289). Pathologic complete response rate was 11.0% (95% CI, 7.8-15.3%) in the nCT arm and 13.8% (95% CI, 10.1-18.5%) in the nCRT arm ( P =0.33). The downstaging (ypStage 0 to 1) rate was 40.8% (95% CI, 35.1-46.7%) in the nCT arm and 45.6% (95% CI, 39.7-51.7%) in the nCRT arm ( P =0.27). nCT was associated with lower perioperative distant metastases rate (0.7% vs. 3.1%, P =0.03) and preventive ileostomy rate (52.2% vs. 63.6%, P =0.008) compared with nCRT. Four patients in the nCT arm received salvage nCRT because of local disease progression after nCT. Two patients in the nCT arm and 5 in the nCRT arm achieved complete clinical response and were treated with a nonsurgical approach. Similar results were observed in subgroup analysis.
nCT achieved similar pCR and downstaging rates with lower incidence of perioperative distant metastasis and preventive ileostomy compared with nCRT. CAPOX could be an effective alternative to neoadjuvant therapy in LARC with uninvolved MRF. Long-term follow-up is needed to confirm these results.
7-Met, a derivative of soybean isoflavone, is a natural flavonoid compound that has been reported to have multiple signaling pathways regulation effects. This study investigated the therapeutic ...effects of 7-Met on mice with atopic dermatitis induced by fluorescein isothiocyanate (FITC), or oxazolone (OXZ). 7-Met ameliorated FITC or OXZ-induced atopic dermatitis symptoms by decreasing ear thickness, spleen index, mast cell activation, neutrophil infiltration and serum IgE levels in female BALB/c mice. In FITC-induced atopic dermatitis mice, 7-Met reduced Th1 cytokines production and regulated Th1/Th2 balance by downregulating the secretion of thymic stromal lymphopoietin (TSLP) via inactivation of the NF-κB pathway. In OXZ-induced atopic dermatitis, 7-Met functioned through the reduction of Th17 cytokine production. Our study showed that 7-Methoxyisoflavone alleviated atopic dermatitis by regulating multiple signaling pathways and downregulating chemokine production.
To evaluate sintilimab versus placebo in combination with chemotherapy (cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil) as first line treatment of unresectable locally advanced, ...recurrent, or metastatic oesophageal squamous cell carcinoma.
Multicentre, randomised, double blind, phase 3 trial.
66 sites in China and 13 sites outside of China between 14 December 2018 and 9 April 2021.
659 adults (aged ≥18 years) with advanced or metastatic oesophageal squamous cell carcinoma who had not received systemic treatment.
Participants were randomised 1:1 to receive sintilimab or placebo (3 mg/kg in patients weighing <60 kg or 200 mg in patients weighing ≥60 kg) in combination with cisplatin 75 mg/m
plus paclitaxel 175 mg/m
every three weeks. The trial was amended to allow investigators to choose the chemotherapy regimen: cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil (800 mg/m
continuous infusion on days 1-5).
Overall survival in all patients and in patients with combined positive scores of ≥10 for expression of programmed cell death ligand 1.
659 patients were randomly assigned to sintilimab (n=327) or placebo (n=332) with chemotherapy. 616 of 659 patients (93%) received sintilimab or placebo in combination with cisplatin plus paclitaxel and 43 of 659 patients (7%) received sintilimab or placebo in combination with cisplatin plus 5-fluorouracil. At the interim analysis, sintilimab with chemotherapy showed better overall survival compared with placebo and chemotherapy in all patients (median 16.7
12.5 months, hazard ratio 0.63, 95% confidence interval 0.51 to 0.78, P<0.001) and in patients with combined positive scores of ≥10 (17.2
13.6 months, 0.64, 0.48 to 0.85, P=0.002). Sintilimab and chemotherapy significantly improved progression free survival compared with placebo and chemotherapy in all patients (7.2
5.7 months, 0.56, 0.46 to 0.68, P<0.001) and in patients with combined positive scores of ≥10 (8.3
6.4 months, 0.58, 0.45 to 0.75, P<0.001). Adverse events related to treatment occurred in 321 of 327 patients (98%) in the sintilimab-chemotherapy group versus 326 of 332 (98%) patients in the placebo-chemotherapy group. Rates of adverse events related to treatment, grade ≥3, were 60% (196/327) and 55% (181/332) in the sintilimab-chemotherapy and placebo-chemotherapy groups, respectively.
Compared with placebo, sintilimab in combination with cisplatin plus paclitaxel showed significant benefits in overall survival and progression free survival as first line treatment in patients with advanced or metastatic oesophageal squamous cell carcinoma. Similar benefits of sintilimab with cisplatin plus 5-fluorouracil seem promising.
ClinicalTrials.gov NCT03748134.
Understanding and engineering the interface between metal and two-dimensional materials are of great importance to the research and development of nanoelectronics. In many cases the interface of ...metal and 2D materials can dominate the transport behavior of the devices. In this study, we focus on the metal contacts of MoTe2 (molybdenum ditelluride) FETs (field effect transistors) and demonstrate how to use post-annealing treatment to modulate their transport behaviors in a controlled manner. We have also carried out low temperature and transmission electron microscopy studies to understand the mechanisms behind the prominent effect of the annealing process. Changes in transport properties are presumably due to anti-site defects formed at the metal–MoTe2 interface under elevated temperature. The study provides more insights into MoTe2 field effect devices and suggests guidelines for future optimizations.
