Structures and organizations of PSI-AcpPCI supercomplexes from red tidal and coral symbiotic photosynthetic dinoflagellates.

Marine photosynthetic dinoflagellates are a group of successful phytoplankton that can form red tides in the ocean and also symbiosis with corals. These features are closely related to the photosynthetic properties of dinoflagellates. We report here three structures of photosystem I (PSI)-chlorophylls (Chls) a/c-peridinin protein complex (PSI-AcpPCI) from two species of dinoflagellates by single-particle cryoelectron microscopy. The crucial PsaA/B subunits of a red tidal dinoflagellate Amphidinium carterae are remarkably smaller and hence losing over 20 pigment-binding sites, whereas its PsaD/F/I/J/L/M/R subunits are larger and coordinate some additional pigment sites compared to other eukaryotic photosynthetic organisms, which may compensate for the smaller PsaA/B subunits. Similar modifications are observed in a coral symbiotic dinoflagellate Symbiodinium species, where two additional core proteins and fewer AcpPCIs are identified in the PSI-AcpPCI supercomplex. The antenna proteins AcpPCIs in dinoflagellates developed some loops and pigment sites as a result to accommodate the changed PSI core, therefore the structures of PSI-AcpPCI supercomplex of dinoflagellates reveal an unusual protein assembly pattern. A huge pigment network comprising Chls a and c and various carotenoids is revealed from the structural analysis, which provides the basis for our deeper understanding of the energy transfer and dissipation within the PSI-AcpPCI supercomplex, as well as the evolution of photosynthetic organisms.

Insights into the genetic variability and evolutionary dynamics of tomato spotted wilt orthotospovirus in China.

BACKGROUND: Viral diseases are posing threat to annual production and quality of tobacco in China. Recently, tomato spotted wilt orthotospovirus (TSWV) has been reported to infect three major crops including tobacco. Current study was aimed to investigate the population dynamics and molecular diversity of the TSWV. In the current study, to assess and identify the prevalence and evolutionary history of TSWV in tobacco crops in China, full-length genome sequences of TSWV isolates from tobacco, were identified and analyzed. METHODS: After trimming and validation, sequences of new isolates were submitted to GenBank. We identified the full-length genomes of ten TSWV isolates, infecting tobacco plants from various regions of China. Besides these, six isolates were partially sequenced. Phylogenetic analysis was performed to assess the relativeness of newly identified sequences and corresponding sequences from GenBank. Recombination and population dynamics analysis was performed using RDP4, RAT, and statistical estimation. Reassortment analysis was performed using MegaX software. RESULTS: Phylogenetic analysis of 41 newly identified sequences, depicted that the majority of the Chinese isolates have separate placement in the tree. RDP4 software predicted that RNA M of newly reported isolate YNKM-2 had a recombinant region spanning from 3111 to 3811 bp. The indication of parental sequences (YNKMXD and YNHHKY) from newly identified isolates, revealed the conservation of local TSWV population. Genetic diversity and population dynamics analysis also support the same trend. RNA M was highlighted to be more capable of mutating or evolving as revealed by data obtained from RDP4, RAT, population dynamics, and phylogenetic analyses. Reassortment analysis revealed that it might have happened in L segment of TSWV isolate YNKMXD (reported herein). CONCLUSION: Taken together, this is the first detailed study revealing the pattern of TWSV genetic diversity, and population dynamics helping to better understand the ability of this pathogen to drastically reduce the tobacco production in China. Also, this is a valuable addition to the existing worldwide profile of TSWV, especially in China, where a few studies related to TSWV have been reported including only one complete genome of this virus isolated from tobacco plants.

Comparison of Short-Term Outcomes After Robotic Versus Laparoscopic Radical Gastrectomy for Advanced Gastric Cancer in Elderly Individuals: A Propensity Score-Matching Study.

BACKGROUND: Robotic gastrectomy (RG) has been widely used to treat gastric cancer. However, whether the short-term outcomes of robotic gastrectomy are superior to those of laparoscopic gastrectomy (LG) for elderly patients with advanced gastric cancer has not been reported. METHODS: The study enrolled of 594 elderly patients with advanced gastric cancer who underwent robotic or laparoscopic radical gastrectomy. The RG cohort was matched 1:3 with the LG cohort using propensity score-matching (PSM). RESULTS: After PSM, 121 patients were included in the robot group and 363 patients in the laparoscopic group. Excluding the docking and undocking times, the operation time of the two groups was similar (P = 0.617). The RG group had less intraoperative blood loss than the LG group (P < 0.001). The time to ambulation and first liquid food intake was significantly shorter in the RG group than in the LG group (P < 0.05). The incidence of postoperative complications did not differ significantly between the two groups (P = 0.14). Significantly more lymph nodes were dissected in the RG group than in the LG group (P = 0.001). Postoperative adjuvant chemotherapy was started earlier in the RG group than in the LG group (P = 0.02). CONCLUSIONS: For elderly patients with advanced gastric cancer, RG is safe and feasible. Compared with LG, RG is associated with less intraoperative blood loss; a faster postoperative recovery time, allowing a greater number of lymph nodes to be dissected; and earlier adjuvant chemotherapy.

Robotic gastrectomy was reliable option for overweight patients with gastric cancer: a propensity score matching study.

BACKGROUND: The role of minimally invasive surgery using robotics versus laparoscopy in resectable gastric cancer patients with a high body mass index (BMI) remains controversial. METHODS: A total of 482 gastric adenocarcinoma patients with BMI ≥ 25 kg/m2 who underwent minimally invasive radical gastrectomy between August 2016 and December 2019 were retrospectively analyzed, including 109 cases in the robotic gastrectomy (RG) group and 321 cases in the laparoscopic gastrectomy (LG) group. Propensity score matching (PSM) with a 1:1 ratio was performed, and the perioperative outcomes, lymph node dissection, and 3-year overall survival (OS) and disease-free survival (DFS) rates were compared. RESULTS: After PSM, 109 patients were included in each of the RG and LG groups, with balanced baseline characteristics. Compared with the LG group, the RG group had similar intraoperative estimated blood loss [median (IQR) 30 (20-50) vs. 35 (30-59) mL, median difference (95%CI) - 5 (- 10 to 0)], postoperative complications [13.8% vs. 18.3%, OR (95%CI) 0.71 (0.342 to 1.473)], postoperative recovery, total harvested lymph nodes [(34.25 ± 13.43 vs. 35.44 ± 14.12, mean difference (95%CI) - 1.19 (- 4.871 to 2.485)] and textbook outcomes [(81.7% vs. 76.1%, OR (95%CI) 1.39 (0.724 to 2.684)]. Among pathological stage II-III patients receiving chemotherapy, the initiation of adjuvant chemotherapy in the RG group was similar to that in the LG group [median (IQR): 28 (25.5-32.5) vs. 32 (27-38.5) days, median difference (95%CI) - 3 (- 6 to 0)]. The 3-year OS (RG vs. LG: 80.7% vs. 81.7%, HR = 1.048, 95%CI 0.591 to 1.857) and DFS (78% vs. 76.1%, HR = 0.996, 95%CI 0.584 to 1.698) were comparable between the two groups. CONCLUSION: RG conferred comparable lymph node dissection, postoperative recovery, and oncologic outcomes in a selected cohort of patients with BMI ≥ 25 kg/m2.

Non-transgenic, PAMAM co-delivery DNA of interactive proteins NbCRVP and NbCalB endows Nicotiana benthamiana with a stronger antiviral effect to RNA viruses.

BACKGROUND: Viral diseases continue to pose a major threat to the world's commercial crops. The in-depth exploration and efficient utilization of resistance proteins have become crucial strategies for their control. However, current delivery methods for introducing foreign DNA suffer from host range limitations, low transformation efficiencies, tissue damage, or unavoidable DNA integration into the host genome. The nanocarriers provides a convenient channel for the DNA delivery and functional utilization of disease-resistant proteins. RESULTS: In this research, we identified a cysteine-rich venom protein (NbCRVP) in Nicotiana benthamiana for the first time. Virus-induced gene silencing and transient overexpression clarified that NbCRVP could inhibit the infection of tobacco mosaic virus, potato virus Y, and cucumber mosaic virus, making it a broad-spectrum antiviral protein. Yeast two-hybrid assay, co-immunoprecipitation, and bimolecular fluorescence complementation revealed that calcium-dependent lipid-binding (CaLB domain) family protein (NbCalB) interacted with NbCRVP to assist NbCRVP playing a stronger antiviral effect. Here, we demonstrated for the first time the efficient co-delivery of DNA expressing NbCRVP and NbCalB into plants using poly(amidoamine) (PAMAM) nanocarriers, achieving stronger broad-spectrum antiviral effects. CONCLUSIONS: Our work presents a tool for species-independent transfer of two interacting protein DNA into plant cells in a specific ratio for enhanced antiviral effect without transgenic integration, which further demonstrated new strategies for nanocarrier-mediated DNA delivery of disease-resistant proteins.

Molecular modeling and rational design of disulfide-stapled self-inhibitory peptides to target IL-17A/IL-17RA interaction.

Interleukin-17A (IL-17A) is a pro-inflammatory cytokine implicated in diverse autoimmune and inflammatory disorders such as psoriasis and Kawasaki disease. Mature IL-17A is a homodimer that binds to the extracellular type-III fibronectin D1:D2-dual domain of its cognate IL-17 receptor A (IL-17RA). In this study, we systematically examined the structural basis, thermodynamics property, and dynamics behavior of IL-17RA/IL-17A interaction and computationally identified two continuous hotspot regions separately from different monomers of IL-17A homodimer that contribute significantly to the interaction, namely I-shaped and U-shaped segments, thus rendered as a peptide-mediated protein-protein interaction (PmPPI). Self-inhibitory peptides (SIPs) are derived from the two segments to disrupt IL-17RA/IL-17A interaction by competitively rebinding to the IL-17A-binding pocket on IL-17RA surface, which, however, only have a weak affinity and low specificity for IL-17RA due to lack of the context support of intact IL-17A protein, thus exhibiting a large flexibility and intrinsic disorder when splitting from the protein context and incurring a considerable entropy penalty when rebinding to IL-17RA. The U-shaped segment is further extended, mutated and stapled by a disulfide bridge across its two strands to obtain a number of double-stranded cyclic SIPs, which are partially ordered and conformationally similar to their native status at IL-17RA/IL-17A complex interface. Experimental fluorescence polarization assays substantiate that the stapling can moderately or considerably improve the binding affinity of U-shaped segment-derived peptides by 2-5-fold. In addition, computational structural modeling also reveals that the stapled peptides can bind in a similar mode with the native crystal conformation of U-shaped segment in IL-17RA pocket, where the disulfide bridge is out of the pocket for avoiding intervene of the peptide binding.

Value of the Preoperative D-Dimer to Albumin Ratio for Survival and Recurrence Patterns in Gastric Cancer.

BACKGROUND: D-dimer (DDI) and albumin are prognostic markers for numerous cancers; however, the predictive value of the preoperative DDI-to-albumin ratio (DAR) on the survival and recurrence patterns of gastric cancer (GC) remains unclear. OBJECTIVE: The aim of this study was to explore the prognostic value of the DAR in GC. METHODS: Our study included 1766 patients with GC, divided into training and testing cohorts at a ratio of 7:3. Patients were classified into either a high-DAR group (> 0.0145) or low-DAR group (≤ 0.0145) according to the cut-off value of receiver operating characteristic (ROC) curve analysis. The relationship between the DAR and recurrence pattern was analyzed in stage II/III patients. RESULTS: Eight preoperative hematological factors were included and 17 composite inflammatory markers were constructed. ROC and random forest analyses indicated that among 17 markers, DAR was the best predictor for overall survival (OS) in GC (p < 0.01). High DAR was significantly associated with poor OS (hazard ratio [HR] 1.89, p < 0.001) and recurrence-free survival (RFS; HR 1.85, p < 0.001). Subgroup analysis showed no differences in OS and RFS between the high- and low-DAR groups in stage I or pT1/2 or pN0/1 patients; however, in stage II/III or pT3/4 or pN2/3 patients, the high-DAR group had shorter OS and RFS rates than the low-DAR group (p < 0.001). Similar results were found in the testing cohort. According to the multivariate analysis based on the training cohort, five indices, including DAR, cT stage, cN stage, age and body mass index (BMI), were incorporated to establish a nomogram model to predict the long-term prognosis of GC. The model showed comparable forecast performance in predicting OS (C-index: 0.773 vs. 0.786) and RFS (C-index: 0.788 vs. 0.795) compared with pTNM. Recurrence pattern analysis in stage II/III patients showed that the high-DAR group had a higher incidence of peritoneal implantation and early recurrence (ER) than the low-DAR group, and the post-recurrence survival in the high-DAR group was significantly shorter than that in the low-DAR group (p = 0.016). CONCLUSION: The preoperative DAR is a new biomarker for the long-term survival prediction of GC. In advanced GC, a preoperative DAR > 0.0145 aids the timely detection of ER and peritoneal recurrence after surgery, thus guiding individual follow-up strategies.

Evaluation of dynamic recurrence risk for locally advanced gastric cancer in the clinical setting of adjuvant chemotherapy: a real-world study with IPTW-based conditional recurrence analysis.

BACKGROUND: The long-term dynamic recurrence hazard of locally advanced gastric cancer (LAGC) in the clinical setting of adjuvant chemotherapy (ACT) remains unclear. PURPOSE: This study aimed to investigate the dynamic recurrence risk of LAGC in patients who received ACT or not. METHODS: The study assessed data from patients with LAGC who underwent radical gastrectomy between January, 2010 and October, 2015. Inverse probability of treatment weighting (IPTW) was performed to reduce selection bias between the ACT and observational (OBS) groups. Conditional recurrence-free survival (cRFS) and restricted mean survival time (RMST) were used to assess the survival differences. RESULTS: In total, 1,661 LAGC patients were included (ACT group, n = 1,236 and OBS group, n = 425). The recurrence hazard gradually declined; in contrast, cRFS increased with RFS already accrued. Following IPTW adjustment, the cRFS rates were higher in the ACT group than those in the OBS group for patients at baseline or with accrued RFS of 1 and 2 years (p˂0.05). However, the cRFS rates of the ACT group were comparable with those of the OBS group for patients with accrued RFS of 3 or more years (p > 0.05). Likewise, the 5-year △RMST between the ACT and OBS groups demonstrated a similar trend. Moreover, the hematological metastasis rate of the ACT group was significantly lower than that of the OBS group for patients at baseline or with accrued RFS of 1 and 2 years, respectively (p˂0.05). CONCLUSIONS: Although ACT could provide substantial benefits for patients with LAGC, the differences in recurrence hazard between the ACT and OBS groups may attenuate over time, which could help guide surveillance and alleviate patients' anxiety. Further prospective large-scale studies are warranted.

Three-dimensional multiphysics coupling numerical simulation of a proton conductor solid oxide fuel cell based on multi-defect transport.

The conductivity of the electrolyte of a proton conductor solid oxide fuel cell is not only related to temperature, but also related to the humidity and oxygen partial pressure of the cathode and anode. The gas partial pressure and temperature of the cell have significant inhomogeneity in three-dimensional space, so it is extremely important to develop a multi-field coupled three-dimensional model to explore the electrochemical performance of the cell. In this study, a model is constructed that takes into account macroscopic heat and mass transfer, microscopic defect transport, and the reaction kinetics of defects. The results show that for thin cathodes, the ribs significantly affect the oxygen partial pressure and the concentration of defects on the cathode side. On both sides of the electrolyte membrane, the concentration of hydroxide ions increases with increasing gas humidity. The hydroxide ion concentration increases along the flow direction, but the concentration of O-site small polarons increases on the anode side and decreases on the cathode side. The conductivity of hydroxide ions is more sensitive to the humidity of the anode side, while the conductivity of O-site small polarons is more sensitive to the humidity of the cathode side. Increasing the humidity of the cathode side results in a significant decrease in the conductivity of the O-site small polarons. The contribution of the conductivity of oxygen vacancies to the total conductivity is negligible. The total conductivity on the cathode side is greater than that on the anode side; it is dominated by hydroxide ions on the anode side, and co-dominated by hydroxide ions and O-site small polarons on the cathode side. Increasing temperature significantly increases both partial and total conductivity. When hydrogen depletion occurs, the partial conductivities and the total conductivity exhibit a sharp increase downstream of the cell.

Oncological outcomes of laparoscopic versus open radical total gastrectomy for upper-middle gastric cancer after neoadjuvant chemotherapy: a study of real-world data.

BACKGROUND: Laparoscopic technique has been increasingly used in gastrectomy, but the safety and feasibility of the laparoscopic total gastrectomy (LTG) for advanced proximal gastric cancer (PGC) after neoadjuvant chemotherapy (NAC) is unclear. METHODS: A retrospective analysis of 146 patients who received NAC followed by radical total gastrectomy at Fujian Medical University Union Hospital from January 2008 to December 2018 was performed. The primary endpoints were long-term outcomes. RESULTS: The patients were divided into two groups: 89 were in the LTG group and 57 were in the open total gastrectomy (OTG) group. The LTG group had a significantly shorter operative time (median 173 min vs. 215 min, p < 0.001), less intraoperative bleeding (62 ml vs. 135 ml, p < 0.001), higher total lymph node (LN) dissections (36 vs 31, p = 0.043), and higher total chemotherapy cycle completion rate (≥ 8 cycles) (37.1% vs. 19.7%, p = 0.027) than OTG. The 3-year overall survival (OS) of the LTG group was significantly higher than that of the OTG group (60.7% vs. 35%, p = 0.0013). Survival with inverse probability weighting(IPW) correction for Lauren type, ypTNM stage, NAC schemes and the times at which the surgery was performed showed that there was no significant difference in OS between the two groups (p = 0.463). Postoperative complications (25.8% vs. 33.3%, p = 0.215) and recurrence-free survival (RFS) (p = 0.561) between the LTG and OTG groups were also comparable. CONCLUSION: In experienced gastric cancer surgery centers, LTG is recommended as the preferred option for such patients who performed NAC, owing to its long-term survival is not inferior to OTG, and it offers less intraoperative bleeding, better chemotherapy tolerance than conventional open surgery.

Comparison of robotic versus laparoscopic versus open distal gastrectomy for locally advanced gastric cancer: a prospective trial-based economic evaluation.

IMPORTANCE: It is largely unclear whether robotic distal gastrectomy (RDG) is cost-effective for locally advanced gastric cancer (LAGC). OBJECTIVE: To evaluate the cost-effectiveness of RDG, laparoscopic distal gastrectomy (LDG), and open distal gastrectomy (ODG) for patients with LAGC. DESIGN, SETTING, AND PARTICIPANTS: Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. A decision-analytic model was constructed to evaluate the cost-effectiveness of RDG, LDG, and ODG. EXPOSURES: RDG, LDG, and ODG. MAIN OUTCOMES AND MEASURES: Incremental cost-effectiveness ratio (ICER) and quality-adjusted life year (QALY). RESULTS: This pooled analysis of two randomized controlled trials included 449 patients: 117, 254, and 78 patients in the RDG, LDG, and ODG groups, respectively. After IPTW, RDG demonstrated its priority in terms of less blood loss, postoperative length, and complication rate (all P < 0.05). RDG also showed higher QOL with more cost, representing an ICER of $85,739.73 per QALY and $42,189.53 per QALY compared to LDG and ODG, respectively. In probabilistic sensitivity analysis, RDG achieved the best cost-effectiveness for patients with LAGC only when the willingness-to-pay threshold was > $85,739.73 per QALY, which significantly exceeded 3 times Chinese per capita GDP. Furthermore, one of the most important factors was the indirect costs of robotic surgery in terms of the cost-effectiveness of RDG compared to that of LDG or ODG. CONCLUSIONS AND RELEVANCE: Although improved short-term outcomes and QOL were seen in patients underwent RDG, the economic burden should be considered in the clinical decision-making regarding robotic surgery use for patients with LAGC. Our findings may vary in different health care settings and affordability. Trial registration CLASS-01 trial (ClinicalTrials.gov, CT01609309) and FUGES-011 trial (ClinicalTrials.gov, NCT03313700).

Association between sleep disorders during pregnancy and risk of postpartum depression: a systematic review and meta-analysis.

Sleep disorders are common among pregnant females. However, its association with postpartum depression (PPD) is unknown. We aimed to assess if sleep disorders during pregnancy increase the risk of PPD by a systematic review. The databases of PubMed, CENTRAL, ScienceDirect, Embase, and Google Scholar were searched for studies reporting the association between any type of sleep disorder during pregnancy and the risk of PPD. Effect sizes were pooled in a random-effects model. Sixteen studies with data of 12,614 women were included. Meta-analysis indicated that sleep disorders during pregnancy resulted in a statistically significant increased risk of PPD (OR: 2.36 95% CI: 1.72, 2.32). The overall result had high heterogeneity (I2 = 84%). Sub-group analysis based on study location (Asian vs Western), sample size (> 500 vs < 500), depression scale, and PPD assessment time did not change the results. However, we found that only poor sleep quality but not insomnia was associated with PPD. The risk was also increased only with sleep disorders measured in the 3rd trimester but not for the 1st and 2nd trimesters. Evidence suggests that sleep disorders during pregnancy may increase risk of PPD. The risk is high for sleep disorders occurring in the 3rd trimester. Based on these findings, there is a need for thorough screening and subsequent corrective measures to ensure adequate and quality sleep among pregnant females.

Evaluation of the anti-viral efficacy of three different dsRNA nanoparticles against potato virus Y using various delivery methods.

Nanoparticles (NPs) derived from RNA interference (RNAi) are considered a potentially revolutionary technique in the field of plant protection in the future. However, the application of NPs in RNAi is hindered by the conflict between the high cost of RNA production and the large quantity of materials required for field application. This study aimed to evaluate the antiviral efficacy of commercially available nanomaterials, such as chitosan quaternary ammonium salt (CQAS), amine functionalized silica nano powder (ASNP), and carbon quantum dots (CQD), that carried double-stranded RNA (dsRNA) via various delivery methods, including infiltration, spraying, and root soaking. ASNP-dsRNA NPs are recommended for root soaking, which is considered the most effective method of antiviral compound application. The most effective antiviral compound tested was CQAS-dsRNA NPs delivered by root soaking. Using fluorescence, FITC-CQAS-dsCP-Cy3, and CQD-dsCP-Cy3 NPs demonstrated the uptake and transport pathways of dsRNA NPs in plants when applied to plants in different modes. The duration of protection with NPs applied in various modes was then compared, providing references for evaluating the retention period of various types of NPs. All three types of NPs effectively silenced genes in plants and afforded at least 14 days of protection against viral infection. Particularly, CQD-dsRNA NPs could protect systemic leaves for 21 days following spraying.

Delta computed tomography radiomics features-based nomogram predicts long-term efficacy after neoadjuvant chemotherapy in advanced gastric cancer.

BACKGROUND AND OBJECTIVE: No effective preoperative tool is available for predicting the prognosis of advanced gastric cancer (AGC) treated by neoadjuvant chemotherapy (NAC). We aimed to explore the association between change values ("delta") in the radiomic signatures of computed tomography (CT) (delCT-RS) before and after NAC for AGC and overall survival(OS). METHODS AND DESIGN: A total of 132 AGC patients with AGC were studied as a training cohort in our center, and 45 patients from another center were used as an external validation set. A radiomic signatures-clinical-nomogram(RS-CN) was established using delCT-RS and preoperative clinical variables. The prediction performance of RS-CN was evaluated using the area under the receiver operating characteristic (ROC)curve (AUC values), time-dependent ROC, decision curve analysis(DCA) and C-index. RESULTS: Multivariable Cox regression analyses showed that delCT-RS, cT-stage, cN-stage, Lauren-type and the value of variation of carcinoma embryonic antigen (CEA) between NAC were independent risk factors for 3-year OS of AGC. In the training cohort, RS-CN had a good prediction performance for OS (C-Index 0.73) and AUC values were significantly better than those of delCT-RS, ypTNM-stage and tumor regression grade(TRG) (0.827 vs 0.704 vs 0.749 vs 0.571, p < 0.001). DCA and time-dependent ROC of RS-CN were better than those of ypTNM stage, TRG grade and delCT-RS. The prediction performance of the validation set was equivalent to that of the training set. The cut-off (177.2) of RS-CN score was obtained from X-Tile software, a score of > 177.2 was defined as high-risk group(HRG), and scores of ≤ 177.2 were defined as the low-risk group(LRG). The 3-year OS and disease free survival(DFS) of patients in the LRG were significantly better than those in the HRG. Adjuvant chemotherapy(AC) can only significantly improve the 3-year OS and DFS of the LRG. (p < 0.05). CONCLUSIONS: Our nomogram based on delCT-RS has good prediction of prognosis before surgery and helps identify patients that are most likely to benefit from AC. It works well in precise and individualised NAC in AGC.

[Therapeutic potential of targeting SIRT1 for the treatment of Alzheimer's disease].

Silent information regulator 1 (SIRT1) is one of the seven mammalian proteins of the sirtuin family of NAD+-dependent deacetylases. SIRT1 plays a pivotal role in neuroprotection and ongoing research has uncovered a mechanism by which SIRT1 may exert a neuroprotective effect on Alzheimer's disease (AD). Growing evidence demonstrates that SIRT1 regulates many pathological processes including amyloid-ß precursor protein (APP) processing, neuroinflammation, neurodegeneration, and mitochondrial dysfunction. SIRT1 has recently received enormous attention, and pharmacological or transgenic approaches to activate the sirtuin pathway have shown promising results in the experimental models of AD. In the present review, we delineate the role of SIRT1 in AD from a disease-centered perspective and provides an up-to-date overview of the SIRT1 modulators and their potential as effective therapeutics in AD.

Comparative Chemical Characterization of Potato Powders Using 1H NMR Spectroscopy and Chemometrics.

This study presents the metabolic profiling of potato powders obtained through various processing procedures and commercially available potato powders. The metabolic fingerprinting was conducted using 1H NMR-based metabolomics coupled with machine learning projections. The results indicate hot air-dried potatoes have higher fumarate, glucose, malate, asparagine, choline, gamma aminobutyric acid (GABA), alanine, lactate, threonine, and fatty acids. In comparison, steam-cooked potatoes have higher levels of phenylalanine, sucrose, proline, citrate, glutamate, and valine. Moreover, the contents of metabolites in processed potatoes in this study were higher than those found in commercial potato powders, regardless of the drying or cooking methods used. The results indicate that a new processing technique may be developed to improve the nutritional value of potatoes.

Proteome-wide analysis of lysine 2-hydroxyisobutyrylation in Frankliniella occidentalis.

BACKGROUND: Lysine 2-hydroxyisobutyrylation (Khib) is a novel and conserved post-translational modification (PTM). Frankliniella occidentalis are economically important agricultural pests globally and also notorious for vectoring destructive plant viruses. To better study the disease transmission mechanism of F. occidentalis, it is necessary to conduct in-depth analysis of it. So far, no Khib modification of insects has been reported. RESULTS: In this study, a proteome-wide analysis of Khib modifications in F. occidentalis was analyzed for the first time through the combination of high performance liquid chromatography fractionation technology and 2-hydroxyisobutyrylated peptide enrichment and other advanced technologies, 4093 Khib sites were identified on 1125 modified proteins. Bioinformatics and functional enrichment analyses showed that Khib-modified proteins were significantly enriched in many cell compartments and pathways, especially related to various cellular components and biological processes, and were more concentrated in ribosomes and proteasome subunits, involved in energy metabolism, protein synthesis and degradation, compared to the other nine species including Japonica rice, Homo sapiens, P. patens, Botrytis, Ustilaginoidea virens, Saccharomyces cerevisiae, T. gondii, C. albicans, and F. oxysporum. And Khib sites on virus-interacting insect proteins were discovered for the first time, such as cyclophilin and endoCP-GN. CONCLUSIONS: After three repeated experiments, we found a total of 4093 Khib sites on 1125 proteins. These modified proteins are mainly concentrated in ribosomes and proteasome subunits, and are widely involved in a variety of critical biological activities and metabolic processes of F. occidentalis. In addition, for the first time, Khib modification sites are found on the proteome of F. occidentalis, and these sites could be acted as for the virus interaction, including cyclophilin and endoCP-GN. The global map of 2-hydroxyisobutyrylation in thrips is an invaluable resource to better understand the biological processes of thrips and provide new means for disease control and mitigation of pest damage to crops.

Scaling-up and proteomic analysis reveals photosynthetic and metabolic insights toward prolonged H2 photoproduction in Chlamydomonas hpm91 mutant lacking proton gradient regulation 5 (PGR5).

Clean and sustainable H2 production is crucial to a carbon-neutral world. H2 generation by Chlamydomonas reinhardtii is an attractive approach for solar-H2 from H2O. However, it is currently not large-scalable because of lacking desirable strains with both optimal H2 productivity and sufficient knowledge of underlying molecular mechanism. We hereby carried out extensive and in-depth investigations of H2 photoproduction of hpm91 mutant lacking PGR5 (Proton Gradient Regulation 5) toward its up-scaling and fundamental mechanism issues. We show that hpm91 is at least 100-fold scalable (up to 10 L) with continuous H2 collection of 7287 ml H2/10L-HPBR in averagely 26 days under sulfur deprivation. Also, we show that hpm91 is robust and active during sustained H2 photoproduction, most likely due to decreased intracellular ROS relative to wild type. Moreover, we obtained quantitative proteomic profiles of wild type and hpm91 at four representing time points of H2 evolution, leading to 2229 and 1350 differentially expressed proteins, respectively. Compared to wild type, major proteome alterations of hpm91 include not only core subunits of photosystems and those related to anti-oxidative responses but also essential proteins in photosynthetic antenna, C/N metabolic balance, and sulfur assimilation toward both cysteine biosynthesis and sulfation of metabolites during sulfur-deprived H2 production. These results reveal not only new insights of cellular and molecular basis of enhanced H2 production in hpm91 but also provide additional candidate gene targets and modules for further genetic modifications and/or in artificial photosynthesis mimics toward basic and applied research aiming at advancing solar-H2 technology.

Field application of nanoliposomes delivered quercetin by inhibiting specific hsp70 gene expression against plant virus disease.

BACKGROUND: The annual economic loss caused by plant viruses exceeds 10 billion dollars due to the lack of ideal control measures. Quercetin is a flavonol compound that exerts a control effect on plant virus diseases, but its poor solubility and stability limit the control efficiency. Fortunately, the development of nanopesticides has led to new ideas. RESULTS: In this study, 117 nm quercetin nanoliposomes with excellent stability were prepared from biomaterials, and few surfactants and stabilizers were added to optimize the formula. Nbhsp70er-1 and Nbhsp70c-A were found to be the target genes of quercetin, through abiotic and biotic stress, and the nanoliposomes improved the inhibitory effect at the gene and protein levels by 33.6 and 42%, respectively. Finally, the results of field experiment showed that the control efficiency was 38% higher than that of the conventional quercetin formulation and higher than those of other antiviral agents. CONCLUSION: This research innovatively reports the combination of biological antiviral agents and nanotechnology to control plant virus diseases, and it significantly improved the control efficiency and reduced the use of traditional chemical pesticides.

[Research strategies and methods for precious animal medicine substitutes].

Animal medicine is a large category of Chinese medicinecommonly used in clinical practice and has important scientific and therapeutic value. Animal medicine isscarcer than herbal medicine. In recent years, with the vigorous development of traditional Chinese medicine(TCM),the contradiction between the increasing industrial demand andsupply of scarce and even endangered medicinal animals has become increasingly prominent. The continuous lack of medicinal animal resources affects the clinical demandandalso causes serious damage to the ecological environment. Only relying on artificial breeding is not enough to alleviate the current condition of depletion. In the face of this dilemma, it is a major challenge for the current industrial development to protect animal resources and meet clinical and industrial needs with "available medicines". The application of substitutes for animal medicines isthe key focus to alleviate this problem, and it is also the key scientific issue to be solved urgently in the modernization of TCM. This paper summarizedand reviewedthe history, current situation, strategies, and methods of animal medicinesubstitution and put forward the point of view of "similar chemical characteristics, similar efficacy, and higher safety" to provide references for scientific substitution and resource protection of rare animals.